Theories of growth and development

GOOD MORNING

Its not about how hard you hit. It’s about how hard you can get hit and keep moving forward; how much you can take and keep moving forward. That’s how winning is done!....

Sylvester Stallone, Rocky Balboa .

http://www.goodreads.com/author/show/67470.Sylvester_Stallone

http://www.goodreads.com/work/quotes/10446115

“GROWTH & DEVELOPMENT”

Theories & Principles

3

CONTENTS Introduction Mechanism of bone growth Deposition and Resorption Growth fields Growth sites Growth centers Remodeling Molecular biology of bone

remodeling

4

Growth movement

1. Cortical Drift 2. Displacement

Principle of ‘Area relocation’ Enlow V principle

Trajectories of bones

1. Trajectories in maxilla

2. Trajectories in mandible

5

Changing concepts & hypothesis of craniofacial growth-

1. Evolution of theories

2. The Remodelling theory (Brash 1930s)

3. The Genetic concept (Brodie 1940s)

4. The Sutural hypothesis ( Sicher 1941)

6

5. The Cartilaginous theory (Scott 1950s)

6. The Functional Matrix theory (Moss 1962)

7. Neurotrophism

8. The Cybernetics theory (Alexandre Petrovic 1970)

9. Conclusion

10. References

7

INTRODUCTION

Growth and development are two integral process which defines the existence of life.

Growth of an organism is the interplay between its genetic constitution and environment in which it thrives.

8

Assessment of growth revels about the general health of the individual and can be used for growth modification treatments.

Growth is a complex process and is not supported by a single theory but is based to a large extent on evolving concepts concerning the biological mechanisms of craniofacial development.

9

MECHANISM OF BONE GROWTH

Bone growth is based on certain basic principles .

Bones do not grow symmetrically but grow by complex differentiation mechanism .

10

All bone growth is a complicated mixture of the two basic principles deposition and resorption .

Deposition and resorption which are carried out by the growth fields comprised of the soft tissue investing the bone.

11

As the fields grows and function differently on different parts of the bone ,the bone undergoes remodeling.

When the amount of bone deposition is greater than the resorption , enlargement of the bone necessitates its displacement.

12

DEPOSITION AND RESORPTIONBone grows by addition of new bone tissue on one side of the bony cortex.

Bone formative changes occurs on the surface facing towards the direction of progressive growth resulting in new bone deposition.

Deposition is observed on the tension side.

13

+ Bone deposition- Bone resorption

14

DEPOSITION AT HISTOLOGICAL LEVEL

Osteoblasts: Bone generating cell

Osteocytes: Mature bone cells, spider shaped and maintain bone tissue

Osteoclasts: Bone destroying cells

Bone Cells

15

OSTEOBLASTS

Osteoblasts are responsible for the synthesis of the organic components of bone matrix (type I collagen, proteoglycans, and glycoproteins).

Osteoblasts depends

on deposition of the inorganic components of bone

http://www.medes.fr/Eristo/Osteoporosis/OsteocytesImage.html

16

OSTEOBLASTS

17

OSTEOCYTES

Osteocytes, which derive from osteoblasts, lie in the lacunae situated between lamellae of matrix.

Only one osteocyte is found in each lacuna.

Lacunae: spaces occupied by osteocyte cell body

18

OSTEOCYTES

19

OSTEOCLASTS

Osteoclasts are very large and branched motile cells.

Dilated portions of the cell body contain from 5 to 50 (or more) nuclei.

20

Osteoclasts are derived from the mononucleated cells

Active osteoblasts stimulate osteoclast activity.

22

BONE RESORPTION

BONE REMODELING

Bone remodeling involves

independent sites of resorption

and formation that change the

size and shape of a bone.

REMODELLING

It involves deposition and resorption

Four types: Biomechanical

Growth remodelling

Haversian remodelling

Pathologic remodelling

24

25

1.Biomechanical- continuous deposition & removal of ions to maintain mineral homeostasis

2.Growth remodelling- constant replacement of bone during childhood

3.Haversian remodelling- secondary process of cortical reconstruction as primary vascular bone is replaced.

4.Pathologic remodelling- regeneration & reconstruction of bone during & following trauma

E.g. The ramus moves posteriorly by the combination of deposition and resorption.

So the anterior part of the ramus gets remodeled

26

FUNCTIONS OF REMODELING1. Progressively change the size of whole

bone

2. Sequentially relocate each component of the whole bone

3. Progressively change the shape of the bone to accommodate its various functions

4. Progressive fine tune fitting of all

the separate bones to each other

and to their contiguous ,growing,

functioning soft tissues.

5. Carry out continuous structural

adjustments to adapt to the

intrinsic and extrinsic changes in

conditions .

29

MOLECULAR BIOLOGY OF BONE REMODELLING

Bone remodeling is accomplished according to the following phases:

1.Activation phase – Different inputs such as a

microfracture , an alteration of mechanical loading sensed by the osteocytes or factors released in the bone microenvironment including IGF-1, TNF-alfa, IL-6 .PTH, activate the lining cells ,which are quiescent osteoblast.

30

•As a consequence lining cells increase their own surface expression of RANKL(Receptor activator of nuclear ligand) which in turn interacts with its receptor RANK , expressed by preosteoclast .

• RANK / RANKL interaction triggers preosteoclast fusion and differentiation towards multinucleated osteoclast.Rucci, N.: Molecular biology of bone remodelling ,

Clinical cases in Mineral and Bone metabolism : 2008;5(1): 49-56

31

2. Resorption phase- • Once differentiated osteoclast polarize ,

adhere to the bone surface and begin to dissolve bone.

• This function requires two steps :Acidification of bone matrix to dissolve inorganic content and release of lysosomal enzymes such as cathepsin K and MMP9 both in charge for degradation of organic content. Once accomplished their function osteoclast undergo apoptosis.

•

•

Rucci, N.: Molecular biology of bone remodelling , Clinical cases in Mineral and Bone metabolism : 2008;5(1): 49-56

32

3.Reverse phase: The reverse cells whose role has not yet been completely clarified performs this phase. Indeed it is known that they are macrophage like cells with a likely function of removal of debris produced during matrix degradation.


33

4.Formation phase: Bone matrix resorption leads to the release of several growth factors herein stored, including bone morphogenetic proteins (BMPs), fibroblast growth factors (FGFs) and transforming growth factor β(TGF β), which are likely responsible for the recruitment of the osteoblasts in the reabsorbed area.

34

Once recruited, osteoblasts produce the new bone matrix, initially not calcified (osteoid) and then they promote its mineralization , thus completing the bone remodeling process.

Unbalance between the resorption and formation phases mirror an incorrect bone remodeling , which in turn affects the bone mass , eventually leading to a pathological condition. Rucci, N.: Molecular biology of bone remodelling , Clinical cases in Mineral and Bone metabolism : 2008;5(1): 49-56

35


Bone remodelling process

36


Osteoblastogenesis process

37

Boskey, A.L., Coleman, R.: Aging and Bone. J Dental Res 2010 ; 89(12): 1333-1348

GROWTH FIELDS

Bone growth is controlled by growth fields.

Distributed in a mosaic like pattern across the surface of a given bone.

They have pacemaking function.

They are either resorptive or depository activity.

38

About one half of the bone is periosteal and the other half endosteal.

If endosteal surface is resorptive then periosteal surface would be depository.

GROWTH SITES

Growth fields having special role in the growth of the particular bone ( grows fast) are called growth sites

e.g. mandibular condyle, maxillary tuberosity, synchondrosis of the basicranium, sutures and the alveolar process.

41

GROWTH SITES

Baume proposed the term growth site for “regions of periosteal or sutural bone formation and modeling resorption adaptive to environmental influences.”

Koski, K. : Cranial growth centres: Facts or fallices? , AJO-DO : Aug 1968: 566-583

42

GROWTH CENTERS

Special areas which are believed to control the overall growth of the bone e.g.mandibular condyle.

Force, energy or motor for a bone resides primarily within its growth centre.

43

The term growth center is widely used in connection with skeletal growth phenomena.

Baume proposed that the term skeletal growth center be used to describe “places of endochondral ossification with tissue separation forces.”

47

Koski, K. : Cranial growth centers: Facts or fallices? , AJO-DO : Aug 1968; 566-583

45

The definition proposed by Baume already implies a spatial limitation that is a growth centre includes only the territory where endochondral ossification takes place .The time element also appears important .

Koski, K. : Cranial growth centres: Facts or fallices? , AJO-DO :Aug 1968: 566-583,

46

Thus the growth centre should mean a place where growth of the skeletal is occurring for a sufficient length of time to make a real contribution to the increase of the skeletal mass beyond the size of the model tissue existing at the onset of the growth centre function.

Koski, K. : Cranial growth centres: Facts or fallices? , AJO-DO : Aug 1968 : 566-583

47

A modified definition would be that a “ growth center is a site of endochondral ossification with tissue separation forces , contributing to the increase of skeletal mass.”


PRINCIPLE OF ‘AREA RELOCATION’

Due to new bone deposition on an existing surface ,all other parts of the structure undergo shifts in relative position – a movement called relocation

48

49

As a result further adaptive bone remodeling is necessary to adjust the shape and size of the area to the new relationship.

•Selective resorption and apposition process functionally remodel the area to conform to the new physiological loading.

ENLOW’S V PRINCIPLE

Most useful and basic concept in facial growth as many facial and cranial bones have a V- shaped configuration.

Bone deposition(+) occurs on the inner side and resorption (-) occurs on the outer surface. 50

EXAMPLE WITH V ORIENTED VERTICALLY

Bone deposition

on lingual side of

coronoid process ,

growth proceeds

and this part of the

ramus increases in

vertical dimension.

51

V ORIENTED HORIZONTALLY

Same deposits of bone also bring about a posterior direction of growth movement.

This produces a backward movement of coronoid processes even though deposit is on the lingual side

52

Same deposits carry base of bone in medial direction .

So, the wider part undergoes relocation into a more narrow part as the whole v moves towards the wide part .

53

54

GROWTH MOVEMENTS Two kinds of growth movements are seen

during the enlargement of craniofacial bases: cortical drift & displacement.

CORTICAL DRIFT: All bones have one common growth principle that is drift.

It was termed by Enlow (1963).

It is growth movement ( relocation or shifting) of an enlarging portion of the bone by the remodelling action of its osteogenic tissues.

DRIFT

It is remodeling process and a combination of deposition and resorption.

If an implant is placed on depository side it gets embedded. Eventually marker becomes translocated from one side of cortex to other.

55

56

The cortical plate can be relocated by simultaneous apposition & resorption procesess on the opposing periosteal and endosteal surfaces.

The bony cortical plate drifts by depositing and resorbing bone substances on the outer & inner surfaces respectively in the direction of growth.

57

If the resorption & deposition takes place at the same times, the thickness of the bone remains constant

Should more bone be deposited than resorbed the thickness of the structure increases

58

During the developmental period, deposition takes place at a slightly faster rate than the resorption , so that the individual bones slowly enlarge.

The teeth follows the drift of the alveolae while the jaw is growing & thus maintain their position within the surrounding bony structure despite the bone displacement.

61

DISPLACEMENT

It is the movement of the whole bone as a unit.

It is a translatory movement of the whole bone caused by surrounding physical forces, and is the second characteristics mechanism of skull growth.

62

The entire bone is carried away from its articular interfaces( sutures , synchondroses, condyle) with adjacent bones.

Displacement is of two types namely:

Primary displacement- As a bone enlarges , it is simultaneously carried away from the other bones in direct contact with it.This creates space within which bony enlargement takes place.

63

It is the physical movement of the whole bone ,as the bone grows & remodels by resorption and apposition.

64

Secondary displacement : It is the movement of a whole bone caused by the separate enlargement of other bones which may be nearby or quite distant.

It is related to enlargement of other bone.

For example: growth in the middle cranial fossa results in the movement of the maxillary complex anteriorly & inferiorly .

66

TRAJECTORIES OF BONEIn 1867 an anatomist named Meyer, with the help of the mathematician Culmann, propounded the Trajectional theory of bone formation.

He pointed out that the alignment of the bony trabeculae in the spongiosa followed definite engineering principles.Graber T.M., Orthodontics-Principles and Practice. 3rd ed. Philadelphia:Saunders;1992.p.133

67

If lines were drawn following discernible columns of oriented bony elements, these lines showed a remarkably similar structure to the trajectories seen in a crane.

Many of these trajectories crossed at the right angles – an excellent arrangement to resist the manifold stresses on the condyle of the femur.

Graber T.M., Orthodontics-Principles and Practice. 3rd ed. Philadelphia:Saunders;1992.p.133

68

In 1870’s Julius Wolff carried this theory one step further. He claimed that the trabecular alignment was due primarily to functional.

A change in the intensity and direction of these forces would produce a demonstrable change in the internal architecture and external form or the bone.

This concept was referred to as “The law of orthogonality”.Graber T.M., Orthodontics-Principles and Practice. 3rd ed. Philadelphia:Saunders;1992.p.133

69

In essence , the law stated that the stresses of tension or pressure on bone stimulate bone formation.

Endochondral bone may respond differently at its growth centre than membranous bone.


70

It has been shown that both tension and pressure can produce loss of bone tissue, that the trabeculae do not form predominantly straight lines .

Many of the so called trajectories are irregular and wavy varying from bone to bone depending on the stresses encountered .


71

Abnormal pressures on bone can cause actual change , as seen on patients with scoliosis who had been treated with Milwaukee brace.

Benninghoff showed that the stress trajectories obeyed no individual bone limits , but rather the demand of the functional forces


72

Changes in functional forces produces measurable changes in bony architecture.

These changes are within the limit of inherent morphogenetic pattern.

Lack of function leads to reduction of density of bone tissue or osteoporosis.Increased function produces a greater density of bone in an area or osteosclerosis . An example is kyphosis

73

TRAJECTORIES OF THE MAXILLA:

The presence of stress trajectories can be demonstrated in the maxilla originating from above the teeth and passing superiorly to the zygomatic or jugal buttress.


74

There are three main vertical trajectories, all arising from the alveolar process and ending in the base of the skull : The canine pillar . The zygomatic pillar . The pterygoid pillar


75

Horizontal reinforcing members include:

Trajectories from: Hard palate, orbital walls ,

zygomatic arches , palatal bone & lesser wing of sphenoid.


77

“Maxillary trajectories”

Vertical pillars

Horizontal pillars

Canine pillar

Malar zygomatic pillar

Pterygoid pillar

78

TRAJECTORIES OF THE MANDIBLE :

The mandible because it is a unit by itself and a movable bone , has a different trabecular alignment from that of the maxilla.


79

Trabecular columns radiate from the beneath the teeth in the alveolar process & join together in a common stress pillar or trajectory system, that terminates in the mandibular condyle .

The thick cortical layer of compact bone along the lower border of the mandible offers the greatest resistance to the bending forces.


80

Other trajectory patterns are seen at the symphysis , at the gonial angle & leading downward from the coronoid process into the ramus and body of the mandible.

These accessory stress trajectories probably are due mainly to the direct effect of the attachment of the muscles of mastication.


EVOLUTION OF THEORIES

82

83

Paradigm It is a conceptual scheme that encompasses individual theories and is accepted by a scientific community as a model and foundation for further research.

Moyers R.E.,Handbook of Orthodontics..4th ed. Year Book Medical Publishers:1988.p.48-50

84

EVOLUTION OF PARADIGM’S

Moyers R.E.,Handbook of Orthodontics..4th ed.Year Book Medical Publishers:1988.p.48-50

85

Various paradigms1920-1940

• More emphasis on structure rather than function.

• Moss subdivided this period:

1. Preradiologic Phase-Emphasis placed on craniometry

2. Radiological phase

• Development of the Genomic Paradigm

Moyers R.E.,Handbook of Orthodontics..4th ed.Year Book Medical Publishers:1988.p.48-50

86

Moss- “Classic Triad”1. Sutures are primary growth sites2. Growth of the cranial vault

occurs only by periosteal deposition

and endosteal resorption.3. All cephalic cartilages are

primary growth centers under direct

genetic control

87

1940-1960

• Craniofacial biology saw an increased emphasis on experimental animal research in an effort to account for the actual mechanism of facial growth.

• Studies were more methodological and conceptual.

• Investigators began to recognize that there is much more variation within the facial region and that this variation could be the result of modifying influences during Ontogeny

88

Technological developments:-

• Use of Radioopaque Implants. • Vital Dyes.• Autoradiography.• In-vivo and In-vitro transplantations.

•By the end of 1950’s two similar approaches were seen within the single Genomic Paradigm: • Comprehensive Approach

• Structurofuntional Approach

89

Comprehensive Approach:

Continued with craniometrics but with more sophisticated hardware including radiographs, cephalostats and software in the form of statistical models.

Structurofunctional Approach:

Concentrated more on “cause and effect relationships” within and among the biologic systems of the Craniofacial complex.

90

By the end of 1950’s the genomic paradigm was put into question

Periosteal and Sutural bone growth were removed from the genomic paradigm and given the status of secondary, compensatory or adaptive phenomena

But due to lack of evidence the genomic paradigm remained dominant and the alternative view that “Function” plays a major role continued to gather momentum.

91

MAINLY DOMINATED BYGENOMIC PARADIGM

92

1960-1980

Formulation of an Alternative paradigm.

--Termed as the “Functional Paradigm” stated that the

Craniofacial complex is highly adaptable to the

functional demands placed on it and its developmental environment.

--Melvin Moss’s “Functional Matrix Hypothesis” is

believed by most craniofacial biologists to be the

alternative paradigm

93

DEVELOPMENT OF AN ALTERNATIVE PARADIGM

94

Moss 10 yrs later released a third paper on the same.

--From then on the “Functional” hypothesis became a topic of theoretical debate involving people like:-

• Moorrees(1972)• Johnston(1976)• Koski(1977)• Wayne Watson(1982)

Debate focused on:• That cephalic cartilages have no intrinsic growth properties.

• The mechanisms by which the capsular matrices(oral,nasal,pharyngeal)assert “morphogenic primacy”

95

--Alexander Petrovic and Associates(1975)• Proposed the cybernetic models of mandibular growth.

1980-2000

• This period saw a confluence of both the genomic

and the functional paradigms.

• A more focused view was developed and merits and demerits of each theory were considered.

96

FUNCTIONAL

MATRIX

REVISITED

PRESENT

97

BONE REMODELLING THEORY BY BRASH (1930)This theory states that bone grows only by

interstitial growth.

The fundamental tenets of this theory are:

Bone grows only by apposition at the surface.

Growth of jaws takes place by deposition of bone at the posterior surfaces of the maxilla and mandible.

This is described as Hunterian growth.

Carlson ,D.S.:Theories of craniofacial growrth in postgenomic era . Semin orthod 2005;11:172-183

98

Calvarium grows through bone deposition on the ectocranial suface of the cranial vault and resorption of bone on the endocranial surface

Bone remodeling theory postulated that the craniofacial skeletal growth takes place by bone remodeling –selective deposition and resorption of bone at its surfaces.

100

THE GENETIC THEORY( 1941)

Genetic theory was given by Brodie.

The genetic theory simply stated simply that genes determine and control the whole process of craniofacial growth.

But the mechanism of action by the genetic unit and the mechanism by which the traits are transmitted were not understood until recently.

101

Genetic concept suggests that the genes supply all the information in growth and development.

This originated with classical Mendelian genetics.

Later with the blending of data from vertebral paleontology created the neo-Darwinian synthesis which is currently accepted paradigm of phylogenetic regulation.

102

Genetic concept stipulates that the genotype supplies all the information required for phenotypic expression.

Moss also stated in his thesis that the whole plan of growth, the various operations carried out , the order and site of growth and their co-ordination with other systems are all embossed in the nucleic acid message.

103

The field of genetics consists of two principle areas :

“Transmission genetics” is characterized by statistical approach and involved only in explaining possible method of transmission.

It is based on Mendelian laws and did not explain about genes or its characteristics.

104

THE SUTURAL HYPOTHESIS

Given by Sicher and Weinmann in 1947 .

According to this theory, sutures ,cartilages and periosteum are responsible for facial growth and were assumed to be under intrinsic genetic control.

Sicher came to the conclusion that sutures were causing most of the growth based on the studies using vital dyes.

105

Essence of the Theory:

According to Sicher, the sutures are the primary determinants of craniofacial growth. The craniofacial skeleton enlarges due to expansible forces exerted by the sutures as they separate.

107

Theory:

He started that all bone forming elements like sutures ,cartilages and periosteum are growth centers like the epiphysis of the long bone.

Sicher called this theory as the sutural dominance theory because he believed that the primary event in sutural growth is proliferation of the connective tissue between the two bones.

108

Proliferation of the sutural connective tissue creates the space for appositional bone growth between the borders of two bones.

Increase in the size of the cranial vault takes place via primary growth of the bone at the sutures, which forces the bones of the vault away from each other.

109

Growth of the midface takes place via intrinsically determined sutural expansion of the circummaxillary suture system, which forces the midface downward and forward.

Mandibular growth takes place via intrinsically determined growth of the cartilage of the mandibular condyle ,which pushes the mandible downward and forward.

110

There is considerable growth occuring in suture and hence from this point of view sutural growth attains significance.

Sicher postulated that bone growth within the various maxillary sutures produces pushing of the bone which results in forward and downward movement of the maxilla.

111

It was believed that the stimulus for bone growth is tension produced by the displacement of the bones.

112

Koski (1968) stated there are two different views regarding the structure of sutures.

The first school or thought (Sicher and Weinmann ) considers sutures as a three layered structure.


113

There is spreading of sutures due to proliferation of middle layer of the sutural tissue.

According to this concept tissue separating force exists in the suture itself.

It stated that the connective tissue between the two bones plays the same role as the cartilage at the bases of the skull and like epiphysis of the long bone

114

The second school of thought (Pritchard ,Scott and Girgis,1956) says the suture as a five layer structure .

Each bone at the suture has its own two layer of periosteum on both sides ant the intervening fifth layer between these periosteal layers.

115

This layer plays a role in adjustment between the bones during the growth .

while the active proliferating role is played by the cambial layers of the periosteum of each bone.

116

It is very clear now from the histological evidenced that the sutural structure is not identical to that of the epiphyseal growth plate.

Sicher also perceived the mandible as a long bone and the mandibular condylar cartilage as comparable to epiphyseal plate of the long bone.

EVIDENCES AGAINST SUTURAL THEORY

118

Trabecular pattern in the bones at the suture change with age ,indicating the changes in the direction of growth it cannot be accepted that suture will have the necessary information for altering growth.

Extirpation of facial sutures has no appreciation effects on the dimensional growth of the skeleton (Sarnat 1963)

119

Shape of sutures have been found to depend on the functional stimulus.( Moss & Salentejin, 1969)

Closure of sutures to be extrinsically determined.( Moss ML, 1954)

Sutural growth can be halted by mechanical forces like clips placed across the sutures.

120

The parallelism of circummaxillary suture so as to effect a forward and downward growth of maxilla is only superficial .

Growth at zygomaticomaxillary suture occurs predominantly in lateral direction .

The direction of growth of maxilla ranges from 0 to 82 degree in relation to SN plane .

It is practically impossible for the suture running in same direction to push the maxilla parallel to the reference plane. (Bjork 1966)

Bjork: Acta odont.scandinav.1966; 24:109-127

121

Conclusion:

Present evidences indicates suture as adaptive growth sites.

Sutural tissues have no tissue separating forces and they are not comparable to growth centers.

122

NASAL SEPTUM THEORY/CARTILAGENOUS THEORY/NASOCAPSULAR THEORY (1950)

James H Scott , an Irish anatomist in 1950 proposed the nasal septum theory as the single and unified theory of craniofacial growth.

123

Essence of theory:

According to this sutures play little role or no direct role in the growth of the craniofacial skeleton .Sutures are considered as merely passive secondary and compensatory sites of bone formation and growth

124

After recognizing the importance of cartilaginous parts of the head , nasal capsule ,mandible and cranial base in prenatal growth.

Scott felt that this cartilaginous development was under genetic control and was of the opinion that they continued to dominate postnatal facial growth also.

125

Scott concluded that nasal septum is mostly active and vital for craniofacial growth both prenatally and postnatally.

The anterioinferior growth of the nasal septal cartilage which is buttressed against the cranial base “pushes” the midface downward and forward.

The cranial base synchondroses causes the growth of the cranial base and Scott compared the condylar cartilage to the cranial base cartilage

126

Discussion: Numerous experimental studies were conducted to address the validity of Scott’s hypothesis .

This theory is based on the fact that cartilage is a pressure adapted tissue and expansion of cartilage provides the force to displace downward and forwards.

.

127

According to Scott ,bone separation must precede before the adaptive sutural bone growth occurs .

The bone separation is because of growth of organs like brain , eyeball or cartilage.

128

Scott is of the opinion that there are two suture system:

Posterior suture system lies behind the maxilla and separates it from palatine ,lateral mass of ethmoid , lacrimal , zygomatic and vomer bones.

Anterior suture system separates premaxilla nasal and vomer bone.

129

Scott said that the nasal cartilage is an extension of the cranial base cartilage and as it grows further, it separates the facial bones from one another and also from the cranial portion .

Thus it allows bone growth to take place at the sutures (frontomaxillary , frontonasal , frontozygomatic and frontozygomaticomaxillary) by surface deposition.

130

Evidences supporting the theory:

Experimental research on rats by Ohyama(1969) -removal of septal cartilage produces deficient growth of snout.

Also supported by research of Burdi , Petrovic , Baume, Latham (1965,1967-1968,1968,1972) respectively .

131

EXPERIMENT BY BURDI , PETROVIC , BAUME, LATHAM (1965,1967-1968,1968,1972) RESPECTIVELY

132

The importance of the septal growth was also seen in impulse to maxillary growth in cleft palate cases.

Failures of the underdeveloped maxillary segment to unite with nasal septum in complete unilateral clefts deprives it of the growth impulse or energy. The normal contra lateral side on the other hand, attained normal growth.

133

Sarnat in (1988)from experiments on rabbit snout concluded that deformity of snout after resection of nasal septum was the result of lack of growth.

Latham (1974) described the role of septomaxillary ligament passing from anterioinferior border of nasal septum to anterior nasal spine and inter maxillary suture in premaxillary region. He stated that the traction through the ligament will exert downward and forward growth of maxilla.

134

Koski(1968) after histological study of nasal septal cartilage found that there is endochondral ossification taking place at septoethmoidal junction.

Hunter and Enlow(1968) –in their growth equivalent theory –emphasizes on relatively lesser response of the endochondral cranial base as opposed to immediate response of the intramembranous cranial vault to external influences

135

Evidence against the theory:

Moss and Bloonberg(1968), Brigit Thilander(1970) found only slight deformity after extirpation of septal cartilage

They concluded that septal cartilage provides only mechanical support for the nasal bones and is not a primary growth center.

136

Two studies were carried out by Gilhus-Moe and Lund in Scandinavia in 1960’s showed that

There are excellent chances that condylar process would regenerate to approx. its original size after trauma In a few there was even a overgrowth of condyle.In a few children there is a reduction in growth after injury maybe due to the trauma to the soft tissues / scarring

Therefore Scott’s hypothesis does not hold true completely.

137

CONCLUSION:At present ,nasal septum theory is still accepted as a reasonable explanation for craniofacial growth.

Nasal septum may be important anterioposterior growth of face because of endochondral growth process occurring at its posterior border.

It is not considered to be an active contributor for vertical development of face.

138

HUNTER & ENLOW’S GROWTH EQUIVALENT

The Hunter-Enlow growth equivalents concepts is an important principle covering the development of the facial skeleton.

As the individual components of the skull develop in different directions ,they must interact directly in order to compensate for the carious growth activities,

This is achieved by growth equivalents which act in opposing directions.

139

These growth equivalents coordinate the different movements of the cranial base ,the nasomaxillary complex and mandible , which are due to development ,and thus determine the adaptive changes in relation to individual parts of the skull.

140

For example, elongation of the anterior cranial base is related with enlargement of the nasomaxillary complex.Disturbances during realization of this growth pattern cause craniofacial anomalies. The disturbance can be related to disproportions of the equivalents in the vertical or horizontal plane

143

THE FUNCTIONAL MATRIX THEORYIntroductionEssence of theoryExplanationNeurotrophismConstraints of functional matrix hypothesis

144

INTRODUCTION

The concept of this theory was introduced first by Vander Klaww(1948-52).

Melvin L. Moss developed the form and function concept into the functional matrix hypothesis.

Introduced in 1962.

145

ESSENCE OF THE THEORY

The functional matrix hypothesis claims that the origin , form , position, growth and maintenance of all skeletal tissues and organ are always secondary ,compensatory and necessary responses to chronologically and morphologically prior events or processes that occur in specifically related nonskeletal tissues ,organs or functioning spaces (functional matrices).

146

The hypothesis as shown that change in size, shape, and location (growth) of all craniofacial skeletal entities are epigenetically( causally related series of processes in external and internal environment) regulated.

147

The epigenetic hypothesis suggests that the post fertilization genome does not contain sufficient information ,such as a blueprint, to regulate all subsequent development.

As structural and functional complexity increases new regulating information is generated.

The interaction of both genomic and epigenetic factors is required to regulate or cause development.

148

Proponents of the functional matrix states that the expansion of the soft tissue matrix is primary and the bone growth is purely secondary and compensatory event. Translation of the various bones of the face is due to volumetric expansion of the encapsulated spaces or tissues.

151

FUNCTIONAL CRANIAL COMPONENT

Functional Cranial Component

One function

Skeletal tissue Vascular tissueMuscle tissueNeural tissue

152

Functional Cranial Component

Tissues and spaces that completely perform a function

Functional matrix

A related skeletal unit that acts biomechanically to

protect and/or support itsfunctional matrix

Skeletal cranial component

1. Periosteal matrix2. Capsular matrix

153

PERIOSTEAL MATRIX

Relates the matrix to those tissues that influence the bone directly through the periosteum.Examples of periosteal matrices includes:

Muscles.Blood vessels and nerves lying in grooves or entering or exiting through foramina.Teeth.

154

Lack of contraction leads to atrophy of the bone.

All the periosteal matrices act homogeneously by means of osseous deposition and resorption.

The muscles are attached either into the skeletal tissue or indirectly by fusion with the outer fibrous layer of periosteum.

Functioning muscles influence developmental changes in the form of skeletal tissue to which they are attached.

155

Affects a microskeletal unit, sphere of influence is usually limited to a part of one bone

Temporalis – coronoid process.

Tooth - alveolar bone.

They act to alter the size or shape or both of the bones.

The growth process that occurs due to periosteal matrix stimulation is called Transformation.

The periosteal matrices stimulation causes growth of the micoskeletal units.

156

CAPSULAR MATRIX

Included in this matrix are those masses and spaces that are surrounded by capsules.

Example:Neural mass with scalp and dura.Orbital mass with supporting tissues of the eyes.

157

Capsules tend to influence macroskeletal units which means portions of several bones are simultaneously affected

Inner surface of calvarium. This sharing of reaction by several adjacent bones constitutes a macroskeletal unit.

158

Each capsule is an envelope which contains a series of functional cranial components ,skeletal units and their related functional matrices and is sandwiched between two covering layers.Examples: neurocranial capsule orofacial capsule

159

Neurocranial capsule:

In this cover consists of skin and duramater ,the neurocapsular matrix consists of the brain , leptomeninges and CSF.

The expansion of the enclosed and protected capsular matrix volume is the primary event in the expansion of the neurocranial capsule.

160

.As the capsule enlarges ,the whole of the included and enclosed functional components, that is the periosteal matrices and the microskeletal units are carried outward in a totally passive manner.

161

The calvarial functional cranial components as a whole are passively and secondarily translated in space.

In experimentally induced or pathological states the periosteal matrices are prevented from exerting their morphogenetic activity.

162

The expansion of the neurocranial capsule is proportional to the increase in neural mass. This can be shown by considering hydrocephaly as an example.

This suggests that the neural skull does not grow first and thus provide space for the expansion of the neural mass rather the growth of neural mass is primary and causes secondary compensatory growth of the skull.

163

Thus the point is simple the neural skull does not grow first and provide space for the secondary expansion of the neural mass rather the expansion of the neural mass is primary event causing growth of the neural skull.

164

Orofacial capsule:

All the functional cranial components of the facial skull arise, grow and maintained within the orofacial capsule.

This surrounds and protects the orophoryngeal functioning spaces, and the volumetric expansion of these spaces serves as a primary morphogenetic extent in facial skull growth.

Moss ML,Salentijin L.:The primary role of functional matrices in facial growth: Am J Orthod june 1969; 55;566-77

165

These spaces are left over as it were, when facial bones, muscles blood vessels and nerves complete their growth. The patency of these spaces are vital in the metabolic demands of the body.

E.g. airway passage (accomplished by a dynamic musculoskeletal postural balance the mechanism) open masticatory cavity

166

SKELETAL UNITS

May be composed of bone, cartilage or tendinous tissue. Each bone is composed of several micro skeletal units

The possible interaction between periosteal matrix and microskeletal units includes pterygoid –gonial angle,temporalis-coronoid process, masseter

167

When the adjoining portions of a number of neighboring bones are united to function as a single cranial component it is termed as macro-skeletal unit .

e.g. Endo cranial surface of the calvaria, maxilla, mandible

The overall skeletal growth is a combination of changes in microskeletal and macroskeletalunits due to stimulation of periosteal and capsular matrices respectively.

168

Coronoid micro skeletal unit – related to functional demands of temporalis.

Angular micro skeletal unit – related to activity of both masseter and medial pterygoid.

Alveolar unit – related to presence of teeth.

Basal micro skeletal unit – related to inferior alveolar neurovascular bundle.

In the mandible we distinguish the following micro skeletal units.

169

These micro skeletal units are relatively independent of each other. The term functional matrix is by no means implies only to soft tissues but also includes muscles, glands, nerves, vessels fat, teeth etc.

Most of the orthodontic therapy is firmly based on the fact that when this functional matrix grows or is moved, the related skeletal unit responds.

170

AGAINST

Spheno-occipital synchondrosisDemonstrates autonomous growth

Nasal cartilageScott- midfacial growth not responsive to external influence

Removal - deficient growthDestruction of cell proliferation potential without cicatrization – Deficient growth

Craniostenosis – premature stenosis of sutures inhibits growth – sutures have some capacity to regulate the activity of functional matrix

171

TRANSMISSION OF FUNCTIONAL STIMULUS TO THE BONE- NEUROTROPHISM

Neurotrophism is a non impulsive transmittive neurofunction involving axoplasmic transport providing for long term interaction between neurons and innervated tissue , which homeostatically regulate the morphological compositional and functional integrity of those tissues.

172

Types of neurotrophism:1.Neuromuscular2.Neuroepithelial3.Neurovisceral

Neuromuscular trophism:Neural innervations are established at myoblast stage. The genetic control cannot reside solely in the functional matrices alone and there is neurotropically regulated homeostatic control of genome and similar neurotrophic mechanism exist for capsular matrix which passively regulate the functional cranial component.

173

Muscle denervation-reinnervation: muscle denervation and reinnervation enable us to diffrentiate effect on muscle tissue associated with loss of impulse conduction and contraction from those due to loss of neurotrophic factors. If motor neurons are sectioned and the muscle subsequently becomes reinnervated there is reformation of neuronal conductive function, this demonstrates neuromuscular trophism.

174

Neuroepithelial trophism:The neurological work of neurotrophism first began in dermatology. The factors which contribute to neuroepithelial trophism are:1. local mechanism operating in areas of high mitotic activity2.Epithelial growth factors.

175

Neurotrophic control of genetic activity: neurotrophic control of genetic activity is demonstrated in many tissues under experimental conditions:Protein synthesis in oral epithelial cells and specific enzymatic sysnthesis in taste buds epithelium appear to be neurotrophically regulated.

176

CURRENT CONCEPTS OF FMH:THE MOLECULAR BASIS

The fmh failed to explain the sequences of events through which the extrinsic stimuli caused adaptive responses in the skeletal structures i.e. the flow of the signals that generated required response.

The new researches focused on intercellular signaling, communication and signal transduction from the molecular matrix to micromolecular matrix.

177

CONCEPT OF MECHANOTRANSDUCTION

Mechanotransduction signifies cellular signal transduction.

It is the process by which macromolecular extrinsic stimuli are converted into cellular signals, which can be internalized by a cell and processed so that a suitable adaptive response can be generated..

179

Altered external environment

Vital cells are pertrubed and leads to

Mechanoreceptors transmits an extracellular physical stimulus into

a receptor cell

Mechantransduction –transduces or tarnsforms the stimulus into an intracellular

signal

Intracellular activation

180

OSSEOUS MECHANOTRANSDUCTION

It is a highly specialized and unique mechanism by which bone cells respond to extrinsic stimuli .It occurs in single bone cells and bone cells are computational elements that function multicellularity as a connected cellular network.

181

The unique nature is highlighted by the following facts:1.Unlike other mechanosensory cells ,bone

cells are not specialized for such stimuli2.These cells shows aneural transmission

of signals3. Bone cells show multiple adaptational

responses to a single force ,in contrast to singular response by other tissue cells

4. The changes brought about by stimuli are confined to a single bone to which the signal is tarnsduced.

182

Osseous mechanotransduction translates the periosteal functional stimulus into a skeletal unit cell signal by two skeletal cellular mechanotasductive process:1.Ionic 2.Mechanical..

Ionic or electrical processes involves some form of ionic transport through the bone cell plasma membrane. The possible process includes stretch activated ion channel ,electrokinetic and electric field strengths .

183

Electric field strength may also be a significant parameter. Electrokinetic stimuli in the range of +-2mv can initiate both osteogenesis and osteocytic action potential

The flow of these ions is thought to occur through the voltage gated channels or gap junctions between the adjacent osteocytes .The passage of K+ ,Ca+ ,Na+, ions across the strained osteocytes have been proved.

184

Mechanical process directly, without the intracellular transductive process may itself be a strong stimulus altering the cellular responses through the the transmembrane molecule integrin ,which may transduct the stimuli directly into the nuclear membrane.

This cytoskeletal lever chain ,connecting to the nuclear membrane may have the potential to activate the osteocytic genome.

185

BONE AS AN OSSEOUS CONNECTED CELLULAR NETWORK

•The term ccn implies a network exists between the adjacent cells of a tissue through specialised structures in the cell membranes.

•The specialized structures includes the tight junction ,gap junctions in cell membrane. These junctions spread stimuli very fast across the connected cell.

•Extensive ccn exists in the bone and that the principle component is the gap junction.

186

•Connexin 43 ,a cytoskeleton protein is the major constituent this network.

•Gap juction not only connects the osteocytes to the nighbouring osteocytes but the superficial osteocytes to periosteal and endosteal osteoblasts too.

•Gap junction allows passage of ionic currents molecules signals.

187

•All osteoblast are also interconnected laterally.

•Vertically they connect periosteal osteoblast with preosteoblastic cells and this in turn is interconnected ,thus each ccn is like a true syncytium and are electrically active.

188

THE FMH AND EPIGENETICS

This concept of moss aims to find a middle path to solve the controversy of genomic versus epigenetic control of biologic processes.

Epigenetics is a term which includes : the sum of all the biochemical, bioelectrical and biophysical parameters-instantaneously present intra ,inter and extracellularly- all of which are produced by the functioning of the cell, tissue, organ or organism itself.

189

It should be noted that these same epigenetic factors serve as an internal environment and must be considered in addition to the classical external environment of genetics.

Moss M.L.:The functional matrix hypothesis and epigenetics:Graber T.M.:Physiologic principles of functional appliances,ST Louis;CV Mosby, 1985;3-4

190

It is postulated that epigenetic factors act upon the products of the genome to regulate all developmental processes leading to the production ,increase and maintenance of biological structural complexity and provides feedback regulation of genome itself.

191

•The fmh denies that the genome of skeletogenic cells contain in and of itself sufficient information to regulate the type, site ,rate, direction and duration of skeletal tissue growth.

•But to be sure the modern epigenticist accepts both the data and fundamental concepts of modern molecular biology.

192

In opposition epigenetics views the genome as providing a set of formal prior intrinsic and necessary causal factors which when combined with efficient proximate extrinsic and necessary epigenetic causal factors together are sufficient to account the regulation of development.

193

VAN LIMBORGH’S COMPROMISE THEORY

Three major viewpoints considered:Sicher’s Scott’sMoss’s

194

CONTROLLING FACTORS IN CRANIOFACIAL GROWTH

INTRINSIC GENETIC FACTOR

Genetic factors inherent to the skull tissues

LOCAL EPIGENETIC FACTORS

Genetically determined influence originating from adjacent structures and spaces ( brain, eyes)

GENERAL EPIGENETIC FACTORS

Genetically determined influences originating from distant structures ( sex hormones)

LOCAL ENVIRONMENTAL FACTORS

Local non genetic influences originating from the external environment( local external pressure, muscle forces etc)

GENERAL ENVIRONMENTAL FACTORS

General non genetic influences originating from external environment ( food ,oxygen)

195

Sicher’s viewCartilageSuturesPeriosteum

Are all growth centers

197

Scott postulates Intrinsic genetic factors affect:

CartilagePeriosteum

while sutures are passive and reactory.

199

Moss is felt to have erred in denying any intrinsic genetic factors in the control of chondrocranial growth and… restricting the control of sutural growth to local epigenetic and environmental factors.

201

VAN LIMBORG’S COMPROMISE

Chondrocranial growth is controlled by intrinsic genetic factors

Desmocranial growth is controlled mainly by local epigenetic factors

Desmocranial factors is also controlled by local environmental factors

General epigenetic and general environmental factors have very little role to play.

203

SERVO SYSTEM THEORY/CYBERNETICS THEORY(1972)

Alexandre Petrovic, explained that the growth of various craniofacial regions is the result of interaction of a series of causal changes and feedback mechanisms.

Based on a series of experiments , Petrovic and coworkers have formulated a cybernetic model for the control of mandibular growth.

204

Essence of the theory:

According to the theory ,control of primary cartilages (mid face) takes a cybernetic form of “command” whereas control of secondary cartilages like condyle is comprised of both direct effect of cell multiplication and also indirect effects.

205

Simply stated, the servo system theory is characterized by the following two principal factors:

(1) The horizontally regulated growth of the midface and anterior cranial base, which provide a constantly changing reference input via the occlusion

206

(2) the rate limiting effect of this midfacial growth on the growth of the mandible.

While growth of the mandibular condyle and of the sutures may be affected directly and indirectly by systemic hormones, growth of these structures is clearly more compensatory and adaptive to the action of extrinsic factors, including local function as well as the growth of other areas of the craniofacial complex.

207

This theory starts with the explanation of cybernetics.

cybernetics is the science of control and communication in the animal and machine.

208

The theory postulates that every thing affects everything and therefore organized living systems never operate in an open loop manner.

Open loop is a type of feedback mechanism. The other type of feedback is closed loop mechanism.

209

The feedback closes the regulation loop of a given system in the following way..

210

According to cybernetics theory ,the behaving organism is not seen as a passive respondent called into action by the changing environmental stimuli but as a dynamic system which continuously generates intrinsic activity for organized interaction with the environment.

211

Cybernetics in craniofacial growth: cybernetics demonstrate the relationship between observational and experimental findings.

Black box: The physiologic system under investigation is represented by the block box .The contents of the black box is usually not known.

212

Feedback signal:It is the function of controlled variable that is compared to the reference input

It is negative in regulator and servo system.

213

Closed loop system: If a physiologic system is designed to maintain a specific correspondence between inputs and outputs, in spite of disturbance .

It is called as closed loop system .

It is characterized by the presence of a feedback loop and comparator state.

214

Closed loop has two variations namely regulator and servo system.Open loop system has no feedback loop or comparator.The regulator: The main input is a constant feature in this system .The comparator detects disturbances and their effects.

215

The servo system : It is also called as follow up system .

The main input is not a constant in this system but varies across in time.

216

Elements of the theory: Command is a signal established independently of the feedback system under scrutiny. It affects the behavior of the controlled system without being affected by the consequences of this behavior.

217

Examples : secretion rates of growth hormones , testosterone ,estrogen , stomatomedin. They are not modulated by variations of craniofacial growth.

218

o References input elements : establish the relationship between the command and reference input. Includes septal cartilage, septo-premaxillary ligament, premaxillary and maxillary bones.

o Reference input is the signal established as a standard of comparison ,eg. Sagittal position of maxilla. Ideally it should be independent of the feedback.

219

The controller is located between the deviation signal and the actuating signal.

The confrontation between the position of the upper and lower dental arch is the comparator of the servosystem.

Activity of the retrodiscal pad and lateral pterygod constitutes the actuating signals. The elastic meniscotemporal and menisco mandibular frenum of the condylar form the retrodiscal pad.

220

The controlled system is between the actuator and controlled variable, i.e. growth of the condylar cartilage through retrodiscal padstimulation.

Controlled variable is the output signal of the servosystem . Best example is a sagittal position of mandible.

221

The gain: the gain of a system is the output divided by input . Gain value greater than one it is called amplification and if its less than one it is called attenuation. The pterygocondylar coupling is an example for gain

222

The disturbance: any input other than the reference required is called a disturbance. It results in deviation of the output signal .for example: increase in hormone secretion results in supplemental lengthening of mandible.

The attractor: this is the final structurally stable state in a dynamic system.

The repeller: this includes all unstable equilibrium states like cusp to cusp occlusal relationship.

223

Theory:

According to this the midface grows downward and forward under the primary influence of the cartilaginous cranial base and nasal septum , influenced principally by the intrinsic cell tissue related properties common to all primary cartilages and mediated by the endocrine system.

Carlson D.S.:Growth modification:from molecules to mandible: reprinted from: McNamara J.A.:Growth modification:What works,what dosen,t and why?,Craniofacial growth series 35,The University of Michigan,Ann Arbor,1999

224

The influence of somatotrophic hormones on the growth of cartilages of nasal septum, sphenooccipital synchondroses and other follows that of a cybernetic form of command pattern.

225

•Related to this event the maxillary dental arch is carried into a slightly more anterior position. this is the first and primary event.

•This causes a minute discrepancy between the upper and lower arches ,which Petrovic referred to as the comparator that is the constantly changing reference point between the positions of the dental arches.

226

Upper arch is the constantly changing reference input.

Second propriorecptors within the periodontal regions and TMJ perceive even a very small occlusal discrepancy and tonically activate the muscles responsible for mandibular protrusion.

Petrovic says the functional appliances will work in the same way when given to stimulate mandibular growth in class 2 malocclusions. .

227

Third activation of jaw protruding muscles (retrodiscal pads and lateral pterygoid) acts directly on the cartilage of the mandibular condyle and indirectly through the vascular supply to the Tmj stimulating the condyle to grow.

The growth in secondary cartilage is like condyle corresponds to local and environmental factors (epigenetic control). Lower arches constitutes the controlled variable

228

Finally the effect of the muscle function and responsiveness of the condylar cartilage is influential both directly and indirectly by the hormonal factors acting principally on the condylar cartilage and on the musculature.

229

This entire cycle is continuously activated as a servomotor as long as the midface upper dental arch continues to grow and mature and appropriate extrinsic hormonal and functional factors remain supportive .

This affects position of mandible .The sagittal postion of mandible depends on the modification of condylar growth by the activity of the retrodiscal pad and lateral pterygoid muscle stimulation.

230

EVIDENCES AGAINST THE THEORY•Goret-Nicaise, Awn (1983) found that the resection of lateral pterygoid muscle fails to diminish condylar growth.

•Das, Meyer, Sicher (1965) found that the occlusion remained unaffected in condylectomy studies.

231

CONCLUSION

Craniofacial growth and development are based to large extent on evolving concepts . At the start these concepts were based on naïve assumptions about the perceived competing roles of heredity and environment ,often framed within the context of the age-old “nature nurture” controversy.

232

The craniofacial biologist tend to believe that there was a single ,overiding mechanism governing the growth of the face and jaw tended to focus on a search for what might be called the HOLY GRAIL of CRANIOACIAL BIOLOGY, a single theory that is both biologically accurate and clinically effective.

233

REFERENCES

•Contemporary orthodontics-William.R.Proffit ,W.Fields,David.M.Sarver,5th edition

•Essential of faciial growth,3th ed – H.Enlow, Hans

•Moyers R.E.,Handbook of Orthodontics..4th ed.Year Book Medical Publishers:1988.p.48-50

234

•Orthodontic diagnosis –Thomas Rakosi , I.Jonas , Thomas Graber ,1st editon

•Orthodontics diagnosis and management of malocclusion and dentofacial deformaties- O.P.Kharbanda 2nd edition

235

•Graber T.M., Orthodontics-Principles and Practice. 3rd ed. Philadelphia:Saunders;1992.p.133

•Moss ML.:Growth of the calvaria in the rats: The determination of osseous morphology: Am J Anat 1954:94;333-62

•Sarnat BG:Postnatal growth of the upper face:Some experimental considerations: The Angle Orthodontist:1963 July:vol 33(3);139-61

236

•Bjork, A: Acta odont.scandinav.1966; 24:109-127

•Koski, K. : Cranial growth centres: Facts or fallices? , AJO-DO : Aug 1968: 566-583

•Das A, Meyer J, Sicher H: X-ray and alizarin studies of the effect of bilateral condylectomy in the rat : Angle Orthod: 1965;35;138-48

237

•Sarnat BG:Postnatal growth of the nose and face after resection of septal cartilage in the rabbit.: Oral Surgery.,1968:26:712-727

•Moss ML , Salentijin L:The primary role of functional matrices in facial growth: Am J Orthod : June 1969; 55;566-77

•Ohyama K:Experimental study on growth and development of dentofacial complex after resection of cartilaginous nasal septum .Bull Tokyo Dent.Uni.,1969:16:157-176

238

•Goret-Nicaise,Awn M:Morphological effects on the rat mandibular condyle of section of the lateral pterygoid muscle:European J Orthod 1983;5;315-321

•Moss M.L:The functional matrix hypothesis and epigenetics:Graber T..:Physiologic principles of functional appliances,ST Louis;CV Mosby, 1985;3-4

239

•Carlson DS:Growth modification:from molecules to mandible: reprinted from: McNamara J.A.:Growth modification:What works,what dosen,t and why?,Craniofacial growth series 35,The University of Michigan,Ann Arbor,1999

•Moss ML:The functional matrix hypothesis revisited: part 1.the role of mechanotransduction.Am J Orthod Dntofacial Orthop 1997;112:8-11

•Moss ML: The functional matrix hypothesis revisited : part 2 the role of an osseous connected cellular network.Am J Orthod Dentofacial Orthop 1997; 112:221-6

240

•Boskey, A.L., Coleman, R: Aging and Bone. J Dental Res 2010 ; 89(12): 1333-1348

•Rucci N: Molecular biology of bone remodelling , Clinical cases in Mineral and Bone metabolism : 2008;5(1): 49-56

•Carlson D.S:Theories of craniofacial growrth in postgenomic era . Semin orthod 2005;11:172-183

Theories of growth and development

Education

Transcript of Theories of growth and development