CARTILAGE AND BONE

CARTILAGE & BONE

• Cartilage & bone are examples of specialized connective tissue

• Both originate from mesoderm and mesenchyme

• The major difference is that cartilage is avascular while bone is vascularized

• Cartilage contains an antiangiogenesis factor that prevents invasion of the tissue by blood vessels

CARTILAGE

• Like all connective tissue, cartilage is composed of cells, intercellular space called ground substance or intercellular matrix and fibers – (collagen)

• The cells of cartilage are chondrocytes• Chondrocytes originate from stellate shaped

mesenchymal cells.• Mesenchymal cells round up and differentiate into

chondroblasts• Chondroblasts synthesize the intercellular matrix

CARTILAGE

• When chondroblasts surround themselves with the intercellular matrix, they become less active and are called chondrocytes

• In fact, when the chondroblasts become entrapped in small areas of the intercellular matrix called lacunae – literally small lakes

Appearance Of Cartilage

Consists of round cells suspended in an extracellular matrix

When fixed, round cells shrink and pull away from matrix

Resultant “empty” space is called a lacuna, appearing as a halo or crescent around the remnants of the cell

Avascular

Cartilage Types

• Cartilage is classified by the components of the matrix• Hyaline (very smooth like a lake)

• no apparent fibers in the matrix• eg. articular cartilages

• Elastic• presence of elastic fibers in the matrix• eg. pinna of ear

• Fibrouspresence of an abundance of type I collagen

bundleseg. intervertebral discs

Cartilage Matrix

•Contains: •hyaluronic acid•chondroitin sulfate•keratan sulfate – •elastin in elastic cartilage•type II collagen•type 1 collagen in fibrocartilage

CARTILAGE MATRIX

• The extracellular matrix consists of fibers and an amorphous ground substance

• Fibers are collagen Type II, elastic and reticular• Ground Substance is composed of GAGs of the

proteoglycans• Hyaluronic Acid• Chondroitin sulfate **• Keratan sulfate

Cartilage Growth & Formation

InterstitialChondrocytes divide secrete matrix, and are pushed apart by the matrix

A positionalcatilage surrounded by perichondriuminnermost layer of cells = chondroblastssecrete matrix materials which are added

on to edge of existent cartilage

GROWTH OF CARTILAGE

• Interstitial Growth – literally from within – chondrocytes undergo mitosis within the lacunae. There are long rows of chondrocytes formed called isogenous clusters. Growth in length of a piece of cartilage is by interstitial growth

• Appositional Growth – New cartilage cells and interstitial matrix are added onto the surface of a piece of cartilage

GROWTH OF CARTILAGE• Appositional Growth continued –• Cartilage is covered by a connective tissue investment called

the perichondrium• The perichondrium consists of two layers, a cellular layer

immediately adjacent to the piece of cartilage & a fibrous layer located more superficially

• The inner cellular layer contains undifferentiated mesenchymal cells that continue to differentiate into chondroblasts and slowly add themselves and the matrix that they produce to the surface of the piece of cartilage

• Blood vessels contained within the perichondruim represent the source of nutrients that diffuse through the ground substance to maintain the chondrocytes

CARTILAGE MATRIX

• The highest concentration of newly synthesized GAGs is in the matrix immediately surrounding the chondroblast or chondrocyte

• Bound Water – Chondroblasts and chondrocytes receive their nutrients by diffusion through the water component & if this life line is compromised, the cells will die

• Because cartilage can do quite well in an avascular environment, when a piece breaks off, it has no trouble surviving and can live for years. It has to be removed surgically

BONE

CALCIFICATION OF CARTILAGE

• As we shall see in a later lecture, a normal process called endochondral ossification in hyaline cartilage models of the long bones in a fetus and in an area of bone called the epiphyseal growth plate is a mechanism of bone formation.

• For now, we shall just look at bone and compare it to cartilage

TERMSMacroscopic

Compact - solid chunk of bone

Trabecular = Spongy = Cancellous

meshwork of bony spicules

Microscopic

Immature = Woven – all bone starts out as immature

irregular arrangement of fibers in matrix

Mature = Lamellar

layered arrangement of fibers in matrix – tree trunk

BONE

• Again like all connective tissue, bone consists of cells, fibers and intercellular matrix

• Bone like cartilage is invested with a connective tissue covering called the periosteum.

• The periosteum contains an outer fibrous layer and an inner cellular layer

BONE• Within the inner cellular layer, there are small spindle-shaped

cells (mesenchymal cells). These are the osteoprogenitor cells.• Within the inner aspect of the fibrous layer, there are

osteoprogenitor cells. • Osteoprogenitor cells and osteoblasts occupy this layer and

it is called the osteogenic layer.• There are also osteoclasts present in the osteogenic layer.• Osteoprogenitor cells can undergo malignant transformation.

This disease is osteogenic sarcoma.

BONE CELLS

• Osteoblasts – differentiate from the mesenchymal cells but UNLIKE the chondroblasts, osteoblasts retain their stellate shape and are found on the surface of a developing spicule of bone

• Osteoblasts make collagen Type I fibers and ground substance

• Ground Substance contains GAGs, glycoproteins and osteonectin which anchors mineral components to collagen fibers & osteocalcin, a calcium-binding protein

BONE CELLS• Immature bone (before it is calcified) is called osteoid and

consists of collagen fibers and ground substance• Mineralization involves deposition of many different minerals

to hydroxyapatite crystals Ca 10(PO4) 6(OH) 3• Vitamin C is necessary for the osteoblast to synthesize

osteoid, i.e. make collagen and is also necessary for fracture repair

• Vitamin D is necessary for proper intestinal absorption of calcium, defect results in rickets in children and osteomalacia in adults. Excess causes bone resorption

• Vitamin A deficiency inhibits bone formation and growth while excess causes a faster rate of ossification of the epiphyseal growth plates. Both deficiency and excess cause small stature

Mineralization of bone

Incresed concentrations of Ca and PO ions in the local matrix are brought about by:

binding of Ca by osteocalcin increases local concentration

osteoblasts stimulated to secrete alkaline phosphatase

alkaline phosphatase => increased Ca accumulation

BONE CELLS

Osteocytes – As osteoblasts make and secrete osteoid around themselves, they get trapped & surrounded by matrix (like falling into cement with arms and legs extended). Since they retain their stellate shape,the matrix hardens around the cytoplasmic processes forming tiny tunnels called caniculi where the cell processes remain

BONE CELLS• Once the cells are trapped in their lacunae, they are called osteocytes• The cytoplasmic processes of osteocytes communicate with each other

within the caniculi via gap junctions• The osteocyte is quite metabolically inactive although some activity does

occur• Osteocytes occupy the most but not the entire lacuna• They have densely stained small irregular nuclei • Osteocytes in their lacunae are surrounded by extracellular fluid called

“bone fluid”• May be different composition from extracellular fluid of other tissues

perhaps due to surface osteocytes & osteoblasts forming some type of “membrane” or barrier that separated bone fluid from other tissue fluids

BONE CELLS – HORMONAL INFLUENCES

• Hormonal control of Calcium Homeostasis• In times of low plasma Calcium, parathyroid hormone is released from the

parathyroid glands• Parathyroid hormone interacts with receptors on osteoclasts and

osteocytes to cause calcium to be released from bone – done through mediation of osteoclast-stimulating factor. Excess PTH resulte in bone being more susceptible to fracture

• Calcitonin- produced by parafollicular cells of thyroid - when blood levels of calcium are normal or high, calcitonin is released from the thyroid gland causing calcium to be absorbed and deposited into bone – does so by eliminating the ruffled border of the osteoclasts

• Pituitary Growth Hormone – stimulates overall growth – epiphyseal plates. Overproduction results in gigantism and deficiency in dwarfism

BONE CELLS• Osteoclasts – these are derived from the peripheral blood monocyte and as such

are part of the monocyte phagocyte system• Large, multinucleated,giant cells formed by the fusion of several monocytes• Major resorbers of bone matrix• Found in depressions on the bone surface called Howship’s lacunae• Contain a ruffled border on the resorptive surface, many mitochindria, Golgi

bodies, vesicles & RER• Clear Zone surrounds the ruffeled border and contains microfilaments which help

osteoclasts maintain contact with the bony surface and also isolates the osteoclastic activity

• Vesicular Zone – exocytotic vesicles that transfer the lysosomal enzymes to the Howship’s Lacula & endocytotic vesicles that transfer degraded bone products from Howship Lacula to the ingerof the cell

• Basal Area- located on the side of the cell opposite the ruffled border – contains most of the organelles

Non-dividing but DNA synthesis does occur

Cells of bone

Osteoprogenitor cells

derived from stem cells of mesenchyme

triggered to become osteoblast

Osteoblasts

appears as a single layer of cuboidal cells lying on surface of developing bone

exocytose alkaline phosphatase rich, membrane bound matrix vesicles that are involved in

mineralization of the matrix

Cells of bone (continued)

Osteocytes

mature bone cell trapped in lacunae in matrix

processes contact those of other osteocytes and osteoblasts, joined by gap junctions

Osteoclasts

large, multinucleated cells found in depressions on the surface of the bone

cells release hydrolytic enzymes that degrade the bone matrix

BONE RESORPTION

• Osteoclasts secrete acid – decalcifies surface layer of bone

• Acid hydrolases, collagenases degrade the organic portion of bone

• Osteoclasts resorb the organic and inorganic residues of the bone matrix and release them into connective tissue capillaries.

LamellaeCircumferential

lining or circling the marrow or outer surface of the bone respectively

Concentric

arranged in concentric circles around the Haversion canal

Interstitial

short arcs in spaces between Haversion systems

COMPACT BONE

• Outer & Inner circumferential lamellae are produced by the periosteum and endosteum and encircle the outer and inner aspects of the bone

• Haversian lamellae are found between the outer and inner circumferential lamellae

• Haversian lamellae form concentric rings around a small canal containing blood vessels and nerves – the canal is called the Haversian Canal and represents the vascular system of the bone

COMPACT BONE

• One Haversian system is also known as an osteon and is separated from other Haversian systems by a cement line

• Each lamella is connected to another by the canaliculi and ultimately with the periosteum and endosteum

• In this manner the innermost osteocytes maintain a connection with the circulatory system. If the system breaks down, the osteocytes die and so does that portion of bone

SPONGY BONE

• This is also mature bone• Unlike compact bone, spongy bone is merely

spicules covered by endosteum• Bone marrow is present between spicules• Found in flat bones of skull

Lab 9 Cartilage and Bone

BONE FORMATION