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The mechanobiology of osteoarthritisTo cite this article Ashvin Thambyah and Neil Broom 2009 IOP Conf Ser Mater Sci Eng 4 012008

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The mechanobiology of osteoarthritis

Ashvin Thambyah and Neil Broom

Biomaterials Laboratory Department of Chemical and Materials Engineering The

University of Auckland

ashvinthambyahaucklandacnz

Abstract In combining biomechanical investigations with microanatomical studies the

authors have found new evidence suggesting a mechanobiological link between the altered

microstructural response of degenerate cartilage to load and the way in which structural

changes develop in the early osteoarthritic joint This paper presents the data and background

for a new hypothesis exploring the initiation and progression of mechanically-driven

osteoarthritic processes

1 Introduction Osteoarthritis (OA) is a degenerative condition of the joint that results in the structural deterioration of

articular cartilage Macroscopic changes in articular cartilage either with age or disease become

apparent with the development of superficial fibrillation and shallow fissures or clefts [12] At higher

magnification there is increased fibril aggregation in the cartilage general matrix and increased

calcification of the osteochondral junction [1-5] In osteoarthritis (OA) mechanically stimulated

biological processes are believed to further degrade cartilage to the extent that is seen in the end-stages

of this disease [67] How this disease is initiated and progresses remains a mystery and one important

reason is because capturing the early- or pre-OA state of the joint tissue remains a challenge

2 The influence of tissue degeneration on joint loading Our experiments investigating the microstructural response of the cartilage matrix to load suggest that

any disruption of the tissue continuum by early degenerative structural changes can cause an altered

redistribution of load across the joint surface [8] Such an alteration reduces the overall lateral

transmission of forces increasing instead the radially-directed forces towards the biologically-active

cartilage-bone junction (Figure 1)

Processing Microstructure and Performance of Materials IOP PublishingIOP Conf Series Materials Science and Engineering 4 (2009) 012008 doi1010881757-899X41012008

ccopy 2009 IOP Publishing Ltd 1

Figure 1 Differential interference contrast optical microscopic images of the indentation-edge region Dotted

lines are superimposed on chondrocyte alignment to denote the way forces are transmitted away from the

directly loaded region (indenter footprint) and into the non-directly loaded cartilage continuum (a) intact-healthy

tissue (b) mildly degenerate (c) moderately degenerate and (d) severely degenerate The schematics to the right

show how degeneration of the cartilage surface layer and matrix alters the magnitude and types of stress that

develop in the biologically-sensitive osteochondral junction region

3 New bone formation in the early osteoarthritic joint The altered internal mechanical environment resulting from changes in the way the forces are

transmitted within a degenerate cartilage matrix may be responsible for some important structural

changes that we have revealed using novel micro-imaging techniques These microstructural studies

showed that new bone formation occurs at the cartilage-bone junction beneath still intact cartilage but

near surface-disrupted sites The evidence for this new bone formation is the presence of lsquocutting

conesrsquo in the cartilage-bone junction near osteoarthritic lesion sites (Figure 2) These cones are classic

morphological features associated with the early stages of primary bone formation We have very

recently established this new bone formation as that indicative of a pre-OA tissue state [9]

Processing Microstructure and Performance of Materials IOP PublishingIOP Conf Series Materials Science and Engineering 4 (2009) 012008 doi1010881757-899X41012008

2

Figure 2 EVIDENCE OF NEW BONE FORMATION Compared with the healthy osteochondral junction

shown in (A) the early osteoarthritic junction (B) shows additional and advancing mineralisation fronts (black

arrows) and the presence of lsquocutting conesrsquo (white arrow) shown here are imaged at the osteochondral junction

of mild to moderately degenerate cartilage-bone tissue These cutting cones originate from the underlying bone

and develop within the zone of calcified tissue (ZCC) [AC = Articular Cartilage Scale bar = 50 microm]

4 The biomechanical pathway for osteoarthritis The fact that bone adaptation is related to the presence of mechanical stimuli and that in the

osteoarthritic joint there is new bone formation allows us to pursue the mechanobiological approach

to explain how OA develops This would involve first defining the mechanical pathway from the

macro-level of joint loading through to the micro-level redistribution of load within the tissue

structure A biomechanical framework would then be available for exploring the manner by which

mechanical stimuli signal bone development at the crucial cartilage-bone junction in the OA joint

Such a pathway is illustrated in Figure 3 using both recently acquired experimental evidence and

theoretical interpretations and forms a working hypothesis for our future work

Figure 3 The theoretical model for OA development is illustrated here showing the important link between

the intrinsic structure of the cartilage-bone tissue and the mechanical environment that is a result of load-bearing

The tissue maintenance loop represents the healthy joint that if affected by deviations in structure or mechanical

load result in an instability that progressively deteriorates the joint [Thambyah A 2005] The challenge is to

track tissue microstructural changes that affect and are affected by mechanical stimulus in the environment and

also determine the mechanical load limits (mechanostat) that influence tissue formation and maintenance

Processing Microstructure and Performance of Materials IOP PublishingIOP Conf Series Materials Science and Engineering 4 (2009) 012008 doi1010881757-899X41012008

3

References [1] Buckwalter JA Lane NE Athletics and osteoarthritis Am J Sports Med 1997 Nov-Dec

25(6)873-81

[2] Buckwalter JA Mankin HJ Articular cartilage degeneration and osteoarthritis repair

regeneration and transplantation Instr Course Lect (Am Acad of Orthop Surg) 1998 47487-

504

[3] Broom N Chen MH Hardy A A degeneration-based hypothesis for interpreting fibrillar

changes in the osteoarthritic cartilage matrix J Anat 2001 199(Pt 6)683-98

[4] Chen MH Broom N On the ultrastructure of softened cartilage a possible model for

structural transformation J Anat 1998 192( Pt 3)329-41

[5] Chen MH Broom ND Concerning the ultrastructural origin of large-scale swelling in articular

cartilage J Anat 1999 194 ( Pt 3)445-61

[6] Burr DB and Radin EL Microfractures and microcracks in subchondral bone are they

relevant to osteoarthrosis Rheum Dis Clin North Am 2003 29(4)675-85

[7] Thambyah A BROOM ND lsquoMicro-anatomical response of cartilage-on-bone to

compression mechanisms of deformation within and beyond the directly loaded matrixrsquo

Journal of Anatomy 209(5) 611-22 2006

[8] Thambyah A BROOM ND lsquoOn How Degeneration Influences Load-Bearing In The

Cartilage-Bone System A Microstructural And Micro-Mechanical Studyrsquo Osteoarthritis

Cartilage 15(12)1410-23 2007

[9] Thambyah A lsquoA hypothesis matrix for studying biomechanical factors associated with the

initiation and progression of posttraumatic osteoarthritisrsquo Medical Hypotheses 64 (6) 1157-

61 2005

Processing Microstructure and Performance of Materials IOP PublishingIOP Conf Series Materials Science and Engineering 4 (2009) 012008 doi1010881757-899X41012008

4

Figure 1 Differential interference contrast optical microscopic images of the indentation-edge region Dotted

lines are superimposed on chondrocyte alignment to denote the way forces are transmitted away from the

directly loaded region (indenter footprint) and into the non-directly loaded cartilage continuum (a) intact-healthy

tissue (b) mildly degenerate (c) moderately degenerate and (d) severely degenerate The schematics to the right

show how degeneration of the cartilage surface layer and matrix alters the magnitude and types of stress that

develop in the biologically-sensitive osteochondral junction region

3 New bone formation in the early osteoarthritic joint The altered internal mechanical environment resulting from changes in the way the forces are

transmitted within a degenerate cartilage matrix may be responsible for some important structural

changes that we have revealed using novel micro-imaging techniques These microstructural studies

showed that new bone formation occurs at the cartilage-bone junction beneath still intact cartilage but

near surface-disrupted sites The evidence for this new bone formation is the presence of lsquocutting

conesrsquo in the cartilage-bone junction near osteoarthritic lesion sites (Figure 2) These cones are classic

morphological features associated with the early stages of primary bone formation We have very

recently established this new bone formation as that indicative of a pre-OA tissue state [9]

Processing Microstructure and Performance of Materials IOP PublishingIOP Conf Series Materials Science and Engineering 4 (2009) 012008 doi1010881757-899X41012008

2

Figure 2 EVIDENCE OF NEW BONE FORMATION Compared with the healthy osteochondral junction

shown in (A) the early osteoarthritic junction (B) shows additional and advancing mineralisation fronts (black

arrows) and the presence of lsquocutting conesrsquo (white arrow) shown here are imaged at the osteochondral junction

of mild to moderately degenerate cartilage-bone tissue These cutting cones originate from the underlying bone

and develop within the zone of calcified tissue (ZCC) [AC = Articular Cartilage Scale bar = 50 microm]

4 The biomechanical pathway for osteoarthritis The fact that bone adaptation is related to the presence of mechanical stimuli and that in the

osteoarthritic joint there is new bone formation allows us to pursue the mechanobiological approach

to explain how OA develops This would involve first defining the mechanical pathway from the

macro-level of joint loading through to the micro-level redistribution of load within the tissue

structure A biomechanical framework would then be available for exploring the manner by which

mechanical stimuli signal bone development at the crucial cartilage-bone junction in the OA joint

Such a pathway is illustrated in Figure 3 using both recently acquired experimental evidence and

theoretical interpretations and forms a working hypothesis for our future work

Figure 3 The theoretical model for OA development is illustrated here showing the important link between

the intrinsic structure of the cartilage-bone tissue and the mechanical environment that is a result of load-bearing

The tissue maintenance loop represents the healthy joint that if affected by deviations in structure or mechanical

load result in an instability that progressively deteriorates the joint [Thambyah A 2005] The challenge is to

track tissue microstructural changes that affect and are affected by mechanical stimulus in the environment and

also determine the mechanical load limits (mechanostat) that influence tissue formation and maintenance

Processing Microstructure and Performance of Materials IOP PublishingIOP Conf Series Materials Science and Engineering 4 (2009) 012008 doi1010881757-899X41012008

3

References [1] Buckwalter JA Lane NE Athletics and osteoarthritis Am J Sports Med 1997 Nov-Dec

25(6)873-81

[2] Buckwalter JA Mankin HJ Articular cartilage degeneration and osteoarthritis repair

regeneration and transplantation Instr Course Lect (Am Acad of Orthop Surg) 1998 47487-

504

[3] Broom N Chen MH Hardy A A degeneration-based hypothesis for interpreting fibrillar

changes in the osteoarthritic cartilage matrix J Anat 2001 199(Pt 6)683-98

[4] Chen MH Broom N On the ultrastructure of softened cartilage a possible model for

structural transformation J Anat 1998 192( Pt 3)329-41

[5] Chen MH Broom ND Concerning the ultrastructural origin of large-scale swelling in articular

cartilage J Anat 1999 194 ( Pt 3)445-61

[6] Burr DB and Radin EL Microfractures and microcracks in subchondral bone are they

relevant to osteoarthrosis Rheum Dis Clin North Am 2003 29(4)675-85

[7] Thambyah A BROOM ND lsquoMicro-anatomical response of cartilage-on-bone to

compression mechanisms of deformation within and beyond the directly loaded matrixrsquo

Journal of Anatomy 209(5) 611-22 2006

[8] Thambyah A BROOM ND lsquoOn How Degeneration Influences Load-Bearing In The

Cartilage-Bone System A Microstructural And Micro-Mechanical Studyrsquo Osteoarthritis

Cartilage 15(12)1410-23 2007

[9] Thambyah A lsquoA hypothesis matrix for studying biomechanical factors associated with the

initiation and progression of posttraumatic osteoarthritisrsquo Medical Hypotheses 64 (6) 1157-

61 2005

Processing Microstructure and Performance of Materials IOP PublishingIOP Conf Series Materials Science and Engineering 4 (2009) 012008 doi1010881757-899X41012008

4

Figure 2 EVIDENCE OF NEW BONE FORMATION Compared with the healthy osteochondral junction

shown in (A) the early osteoarthritic junction (B) shows additional and advancing mineralisation fronts (black

arrows) and the presence of lsquocutting conesrsquo (white arrow) shown here are imaged at the osteochondral junction

of mild to moderately degenerate cartilage-bone tissue These cutting cones originate from the underlying bone

and develop within the zone of calcified tissue (ZCC) [AC = Articular Cartilage Scale bar = 50 microm]

4 The biomechanical pathway for osteoarthritis The fact that bone adaptation is related to the presence of mechanical stimuli and that in the

osteoarthritic joint there is new bone formation allows us to pursue the mechanobiological approach

to explain how OA develops This would involve first defining the mechanical pathway from the

macro-level of joint loading through to the micro-level redistribution of load within the tissue

structure A biomechanical framework would then be available for exploring the manner by which

mechanical stimuli signal bone development at the crucial cartilage-bone junction in the OA joint

Such a pathway is illustrated in Figure 3 using both recently acquired experimental evidence and

theoretical interpretations and forms a working hypothesis for our future work

Figure 3 The theoretical model for OA development is illustrated here showing the important link between

the intrinsic structure of the cartilage-bone tissue and the mechanical environment that is a result of load-bearing

The tissue maintenance loop represents the healthy joint that if affected by deviations in structure or mechanical

load result in an instability that progressively deteriorates the joint [Thambyah A 2005] The challenge is to

track tissue microstructural changes that affect and are affected by mechanical stimulus in the environment and

also determine the mechanical load limits (mechanostat) that influence tissue formation and maintenance

Processing Microstructure and Performance of Materials IOP PublishingIOP Conf Series Materials Science and Engineering 4 (2009) 012008 doi1010881757-899X41012008

3

References [1] Buckwalter JA Lane NE Athletics and osteoarthritis Am J Sports Med 1997 Nov-Dec

25(6)873-81

[2] Buckwalter JA Mankin HJ Articular cartilage degeneration and osteoarthritis repair

regeneration and transplantation Instr Course Lect (Am Acad of Orthop Surg) 1998 47487-

504

[3] Broom N Chen MH Hardy A A degeneration-based hypothesis for interpreting fibrillar

changes in the osteoarthritic cartilage matrix J Anat 2001 199(Pt 6)683-98

[4] Chen MH Broom N On the ultrastructure of softened cartilage a possible model for

structural transformation J Anat 1998 192( Pt 3)329-41

[5] Chen MH Broom ND Concerning the ultrastructural origin of large-scale swelling in articular

cartilage J Anat 1999 194 ( Pt 3)445-61

[6] Burr DB and Radin EL Microfractures and microcracks in subchondral bone are they

relevant to osteoarthrosis Rheum Dis Clin North Am 2003 29(4)675-85

[7] Thambyah A BROOM ND lsquoMicro-anatomical response of cartilage-on-bone to

compression mechanisms of deformation within and beyond the directly loaded matrixrsquo

Journal of Anatomy 209(5) 611-22 2006

[8] Thambyah A BROOM ND lsquoOn How Degeneration Influences Load-Bearing In The

Cartilage-Bone System A Microstructural And Micro-Mechanical Studyrsquo Osteoarthritis

Cartilage 15(12)1410-23 2007

[9] Thambyah A lsquoA hypothesis matrix for studying biomechanical factors associated with the

initiation and progression of posttraumatic osteoarthritisrsquo Medical Hypotheses 64 (6) 1157-

61 2005

Processing Microstructure and Performance of Materials IOP PublishingIOP Conf Series Materials Science and Engineering 4 (2009) 012008 doi1010881757-899X41012008

4

References [1] Buckwalter JA Lane NE Athletics and osteoarthritis Am J Sports Med 1997 Nov-Dec

25(6)873-81

[2] Buckwalter JA Mankin HJ Articular cartilage degeneration and osteoarthritis repair

regeneration and transplantation Instr Course Lect (Am Acad of Orthop Surg) 1998 47487-

504

[3] Broom N Chen MH Hardy A A degeneration-based hypothesis for interpreting fibrillar

changes in the osteoarthritic cartilage matrix J Anat 2001 199(Pt 6)683-98

[4] Chen MH Broom N On the ultrastructure of softened cartilage a possible model for

structural transformation J Anat 1998 192( Pt 3)329-41

[5] Chen MH Broom ND Concerning the ultrastructural origin of large-scale swelling in articular

cartilage J Anat 1999 194 ( Pt 3)445-61

[6] Burr DB and Radin EL Microfractures and microcracks in subchondral bone are they

relevant to osteoarthrosis Rheum Dis Clin North Am 2003 29(4)675-85

[7] Thambyah A BROOM ND lsquoMicro-anatomical response of cartilage-on-bone to

compression mechanisms of deformation within and beyond the directly loaded matrixrsquo

Journal of Anatomy 209(5) 611-22 2006

[8] Thambyah A BROOM ND lsquoOn How Degeneration Influences Load-Bearing In The

Cartilage-Bone System A Microstructural And Micro-Mechanical Studyrsquo Osteoarthritis

Cartilage 15(12)1410-23 2007

[9] Thambyah A lsquoA hypothesis matrix for studying biomechanical factors associated with the

initiation and progression of posttraumatic osteoarthritisrsquo Medical Hypotheses 64 (6) 1157-

61 2005

Processing Microstructure and Performance of Materials IOP PublishingIOP Conf Series Materials Science and Engineering 4 (2009) 012008 doi1010881757-899X41012008

4