This is your

presentation title
 This is your
presentation title
Cartilage
&
Bone
 Cartilage
✘ Tough, durable form of connective tissue
✘ Type II collagen
✘ Characterised by an extracellular membrane (ECM) which contain
high concentrations of glycosaminoglycans and proteoglycans
✘ Consists of chondrocytes located in the lacunae which synthesise
and maintain all ECM components
✘ Avascular & uninnervated
 Perichondrium
✘ Sheath of dense connective tissue that surrounds cartilage and
forms an interface between the cartilage and the tissues supported
by the cartilage
✘ Houses the blood supply serving the cartilage and a small neural
component
8
 Hyaline Cartilage
✘ Most common
✘ semitransparent
✘ In the embryo - forms the temporary skeleton
✘ In adults – articular surfaces of moveable joints, walls of the URT,
ventral ends of ribs which articulate with the sternum, and
epiphyseal plates of long bones which allows for longitudinal bone
growth when stimulated by somatomedins released from the liver
by somatotropin
 Matrix
✘ Firm, hydrated gel of proteoglycans and structural glycoproteins
✘ Comprises ~40% of the dry weight of hyaline cartilage
✘ Aggrecan – a.k.a. cartilage-specific proteoglycan core protein, most
abundant proteoglycan of hyaline cartilage, bind to type II collagen
✘ Chondronectin – glycoprotein which mediates adherence of
chondrocytes to the ECM
 Chondrocytes
✘ Chondroblasts Chondrocytes
(elliptical shape) (round shape)
✘ May appear in groups of ~8 cells that originate from mitotic
divisions of a single chondroblast (isogenous aggregates)

pushed apart and occupy separate lacunae as chondrocytes become

more active in secreting collagens and other ECM components
 Perichondrium
✘ A layer of dense connective tissue which covers all hyaline cartilage
except in the articular cartilage of joints
✘ Essential for the growth and maintenance of cartilage
✘ Outer layer – largely consists of type I collagen
✘ Inner layer – contains mesenchymal stem cells
 Elastic Cartilage
✘ Similar to but more flexible than hyaline cartilage and with
abundant elastic fibres + type II collagen fibrils = yellowish colour
✘ Found in areas where flexible support is required: external ear,
Eustachian tubes, epiglottis, parts of the larynx
 Fibrocartilage
✘ Essentially a mingling of hyaline cartilage + dense connective tissue
✘ Found in areas where support and tensile strength are required and
where tissues are exposed to compressive and shear forces:
intervertebral discs, menisci of knees, sternoclavicular joints, pubic
symphysis
✘ Sparse matrix which contains type II collagen + type I collagen
✘ No distinct perichondrium
Chondrogenesis
 Chondrogenesis
Interstitial growth
✘ Division of preexisting chondrocytes
✘ Occurs during early stages of cartilage formation, in articular
cartilage, and in epiphyseal plates of long bones
Appositional growth
✘ Differentiation of chondrogenic cells in the perichondrium
✘ Results in formation of chondroblasts and/or new chondrocytes, in
turn creating a new layer of cartilage matrix at the periphery
 Bone
✘ Special connective tissue composed of calcified extracellular
material – bone matrix
✘ Provides a storage site for PO4 and Ca (99%)
✘ Regulates blood calcium levels via PTH and calcitonin
✘ 3 major cell types: osteocytes, osteoblasts, osteoclasts
 Bone Matrix
Inorganic Portion (65% of dry weight)
✘ Consists primarily of hydroxyapatite crystals

Organic Portion (35% of dry weight)

✘ Consists primarily of type I collagen (95%)
 Bone Matrix
Periosteum
✘ Layer of noncalcified connective tissue covering bone on its
external surfaces
✘ Composed of an outer fibrous layer and inner cellular
osteoprogenitor (osteogenic) layer
✘ Attached to the bone surface via Sharpey fibres (type I collagen)
✘ Distributes blood vessels to bone
 Bone Matrix
Endosteum
✘ Thin specialised connective tissue that lines the marrow cavities
✘ Supplies osteoprogenitor cells and osteoblasts for bone growth &
repair
 Bone Cells
Osteoprogenitor Cells
✘ Spindle-shaped cells derived from mesenchyme
✘ Located in both periosteum and endosteum where they persist as
stem cells
✘ Can be reactivated later for bone repair
✘ Capable of differentiation into osteoblasts and chondrogenic cells
(at low O2 tensions)
 Then you don’t deserve me at my

If you don’t
love me at my
 Bone Cells
Osteoblasts
✘ Derived from osteoprogenitor cells
✘ Synthesise organic protein components of bone matrix (type I
collagen, proteoglycans, glycoproteins) which are secreted as
osteoid (uncalcified bone matrix) which is mineralised under control
of the osteoblasts
 Bone Cells
Osteoblasts
✘ Produce macrophage colony-stimulating factor (M-CSF) – a
receptor for the activation of nuclear factor kappa B (RANKL)
✘ Produce osteoprotegerin, osteocalcin, osteopontin, osteonectin,
and bone sialoprotein
 Bone Cells
Osteoprotegerin Regulates bone density, affects RANKL
Osteocalcin, Osteonectin For bone mineralisation
Osteopontin Forms sealing zone between osteoclasts
and the subosteoclastic compartment
Bone sialoprotein Binds osteoclasts to ECM

33
 Bone Cells
Osteoblasts
✘ Resemble a layer of cuboidal cells
✘ When synthetically active, have a well-developed RER and Golgi
complex
✘ Become entrapped in lacunae osteocytes
✘ If stimulated by PTH promote osteoclast formation
✘ If stimulated by calcitonin inhibit osteoclast formation
 Bone Cells
Osteocytes
✘ Mature bone cells housed in their own lacunae
✘ Have narrow processes that extend through canaliculi in the
calcified matrix
✘ Maintain communication with each other via gap junctions between
their processes
✘ Through these canaliculi nutrients, metabolites, signal molecules,
and released calcium pass to and from the ECF
 Bone Cells
Osteoclasts
✘ Large, motile, multinucleated cells (~50 nuclei) that resorb bone
✘ Differentiated from blood-borne monocytes of the mononuclear-
phagocyte system
✘ Function to resorb bone (osteolysis)
✘ Reside in depressions known as Howship lacunae which represent
areas of bone resorption
 Bone Cells
M-CSF Stimulates macrophages to undergo
mitosis to form osteoclasts
Nuclear Factor Kappa B (RANKL) Binds to macrophages to differentiate into
osteoclasts

Osteoprotegerin Prohibits RANKL from binding to

macrophages thus prohibiting osteoclast
formation

39
 Bone Cells
Osteoclasts
✘ Those activated by osteoclast-stimulating factor display 4 regions
in electron micrographs:
1. Basal zone – houses most of the organelles
2. Ruffled border – site of active bone resorption (Howship lacuna)
 Bone Cells
Osteoclasts
✘ Those activated by osteoclast-stimulating factor display 4 regions
in electron micrographs:
3. Clear/sealing zone – surrounds the ruffled border, seals the region
of osteolytic activity
4. Vesicular zone – contains exocytotic vesicles that transfer
lysosomal enzymes to Howship lacunae and endocytotic vesicles
that transfer degraded bone products from Howship lacunae to
the interior of the cell
 Bone Classification (Gross)
Spongy/Cancellous Bone
✘ Composed of interconnected trabeculae which surround cavities
filled with bone marrow
✘ Trabeculae contain osteocytes and are lined on both surfaces by a
single layer of osteoblasts
✘ Always surrounded by compact bone
 Bone Classification (Gross)
Compact Bone
✘ Has no trabeculae or bone marrow cavities
 Bone Classification (Micro)
Primary/Immature/Woven Bone
✘ Contains many osteocytes and large, irregularly arranged type I
collagen
✘ Low mineral count
✘ First compact bone produced during fetal development & bone
repair
✘ Replaced by secondary bone except in: tooth sockets, suture lines
in the skull, insertion sites of tendons
 Bone Classification (Micro)
Secondary/Mature/Lamellar Bone
✘ Compact bone of adults
✘ Has a calcified matrix arranged in regular layers (lamellae)
✘ Contains osteocytes in lacunae between, and occasionally within,
lamellae
 Organisation of Lamellae
Haversian systems (osteons)
✘ Long cylindrical structures that run approximately parallel to the
long axis of the diaphysis
✘ Composed of 4-20 lamellae surrounding a central haversian canal
(which contains BVs, nerves, loose connective tissue) and lined by
osteoprogenitor cells and osteoblasts
✘ Often surrounded by an amorphous cementing substance
 Organisation of Lamellae
Haversian systems (osteons)
✘ Interconnected by Volkmann canals which connect to the
periosteum and endosteum and carry the nerve supply
 Organisation of Lamellae
Interstitial lamellae
✘ Irregularly shaped lamellae between haversian systems
✘ Remnants of old remodeled haversian systems
 Organisation of Lamellae
Outer and inner circumferential lamallae
✘ Irregularly shaped lamellae between haversian systems
✘ Remnants of old remodeled haversian systems
 Histogenesis
✘ Occurs by two processes: intramembranous and endochondral
bone formation
✘ Both processes produce bone that appears histologically identical
✘ Histogenesis is accompanied by bone resorption – termed
remodeling, which occurs throughout life
✘ Remodeling is slower in secondary bone
 Histogenesis
Intramembranous Bone Formation
✘ Process by which most of the flat bones are formed
1. Mesenchymal cells condense into primary ossification centres,
differentiate into osteoblasts, and begin secreting osteoids (woven
bone)
2. As appositional bone growth continues and calcification occurs,
osteoblasts become trapped in their own matrix. These centres of
developing bone are called trabeculae
 Histogenesis
Intramembranous Bone Formation
3. Fusion of bony trabeculae produces spongy bone as BVs invade
the area and other undifferentiated mesenchymal cells become
hematopoietic cells forming blood cells of the bone marrow
4. The periosteum and endosteum develop from portions of the
mesenchymal layer that do not undergo ossification
 Histogenesis
Intramembranous Bone Formation
5. Mitotic activity of the mesenchymal cells gives rise to
osteoprogenitor cells which undergo cell division and form more
osteoprogenitor cells or differentiate into osteoblasts within the
inner layer of the developing periosteum
6. Finally, intramembranous bone may be then converted to lamellar
bone
 Histogenesis
Endochondral Bone Formation
✘ Process by which long bones are formed
✘ It begins in a segment of hyaline cartilage that serves as a small
model for the bone
1. Mesenchymal cells condense into primary ossification centres,
differentiate into osteoblasts, and begin secreting osteoids (woven
bone)
2. As appositional bone growth continues and calcification occurs,
osteoblasts become trapped in their own matrix. These centres of
 Histogenesis
Endochondral Bone Formation
A. Requires the presence of a hyaline cartilage model
 Histogenesis
Endochondral Bone Formation
B. Vascularisation of the diaphysis perichondrium (2)
results in the transformation of chondrogenic cells to
osteogenic cells which forms a subperiosteal bone
collar (1) that quickly becomes perforated by
osteoclastic activity. Chondrocytes in the centre of
the cartilage hypertrophy (3) and their lacunae
become confluent.
 Histogenesis
Endochondral Bone Formation
C. The subperiosteal bone collar (1) increases in length
and width. The confluent lacunae are invaded by the
periosteal bud (4). Osteoclastic activity forms a
primitive marrow cavity (5) whose walls are
composed of calcified cartilage (calcified bone
complex). The epiphyses display the beginning of
secondary ossification centres (7).
 Histogenesis
Endochondral Bone Formation
D. The subperiosteal bone collar (1) is now large enough
to support the developing long bone, so that much of
the cartilage has been resorbed except for the
epiphyseal plate (8) and the covering of the
epiphyses (9). Ossification in the epiphyses occurs
from the centre, (10)
 Histogenesis
Endochondral Bone Formation
E. Thus the vascular periosteum (11) does not cover the
cartilaginous surface. Blood vessels (12) enter the
epiphyses, without vascularising the cartilage, to
constitute the vascular network (13) around which
spongy bone will form.
Histogenesis
Zones of Epiphyseal Plates
 Calcification
✘ Stimulated by osteonectin, proteoglycans, and bone sialoprotein
✘ Bone matrix contains high concentrations of Ca2+ which are further
concentrated by osteocalcin and sialoproteins which stimulate
osteoblasts to secrete alkaline phosphatase which concentrate
PO4 ions which in turn further concentrates Ca2+ ions.
✘ Small matrix vesicles are released by the osteoblasts into the bone
matrix which crystallise the CaPO4 within the vesicles
 Calcification
✘ Ca2+ pumps in the matrix vesicle membranes bring in more Ca2+,
concentrating it and forming calcium hydroxyapatite crystals that
grow and eventually puncture the matrix vesicle expelling its
contents.
✘ Calcium hydroxyapatite crystals that become free in the matrix
become the nidi of crystallisation
✘ Released enzymes free phosphate ions that unite with the calcium
forming CaPO4
 Calcification
✘ CaPO4 then begins to calcify the matrix around the nidi of
crystallisation
✘ Water is removed from the matrix, permitting hydroxyapatite
crystals to be deposited into the gaps within the collagen fibrils
✘ The nidi enlarge and fuse with neighbouring nidi, eventually
calcifying the entire matrix
 Bone Remodeling
✘ Bone is constantly being remodeled as necessary for growth and to
adapt to changing stresses in the environment throughout life
✘ Early on, bone development outpaces bone resorption
✘ Later when the epiphyseal plates are closed, ending bone growth,
development and resorption are balanced, regulated by factors
such as calcitonin and PTH
 Fracture Repair
✘ A fracture damages the matrix, bone cells, and BVs in the region
and is accompanied by localised hemorrhage and blood clot
formation
1. Proliferation of osteoprogenitor cells occurs in the periosteum and
endosteum in the vicinity of the fracture, which results in cellular
tissue surrounding the fracture and penetrating between the ends
of the damaged bone
 Fracture Repair
2.Formation of a bony callus occurs both internally and externally at
a fracture site
✘ Fibrous connective tissue and hyaline cartilage are formed in the
fracture zone
✘ Endochondral bone formation replaces the cartilage with primary
bone
✘ Intremembranous bone formation also produces primary bone in
the area
 Fracture Repair
2.Formation of a bony callus occurs both internally and externally at
a fracture site
✘ The irregularly arranged trabeculae of primary bone join the ends
of the fractured bone, forming a bony callus
✘ The primary bone is resorbed and replaced with secondary bone
as the fracture heals
 Joints
1. Synarthroses
✘ Immoveable joints
✘ First sternocostal joint, joints of the skull bones
 Joints
2. Diarthroses/Synovial Joints
✘ Permit maximum movement
✘ Surrounded by a two-layered capsule, enclosing and sealing the
articular cavity which contains synovial fluid (a colourless, viscous
fluid rich in hyaluronic acid & proteins)
 Joints
2. Diarthroses/Synovial Joints
✘ External (fibrous) capsular layer – tough, fibrous layer of dense
connective tissue
✘ Internal (synovial) capsular layer/Synovial membrane – lined by
squamous to cuboidal epithelial cells on its internal surface with
two cell types:
 Joints
2. Diarthroses/Synovial Joints
✘ Type A cells – intensely phagocytic, well-developed Golgi complex
✘ Type B cells – resemble fibroblasts, well-developed RER, probably
secrete synovial fluid
 “
Entia non sunt multiplicanda
praeter necessitatem
Arigathanks
gozaimuch
Exam Time

78
1. What is the major collagen type of cartilage?

A. Type I
B. Type II
C. Type III
D. Type IV
E. Type V

79
 2. Where would you be able to find elastic
cartilage?
A. Larynx
B. Pharynx
C. Symphysis pubis
D. Intervertebral discs

80
3. If fibrocartilage is avascular, where does it get
its nutrients?
A. Formation of new blood vessels
B. Diffusion
C. Catabolism of stored nutrients
D. Adjacent perichondrium

81
 4. Which best describes appositional growth

A. Division of preexisting chondrocytes

B. Differentiation of chondrogenic cells in the perichondrium

82
5. Which glycoprotein mediates adherence of
chondrocytes to the extracellular matrix?
A. Osteonectin
B. Sialoprotein
C. Aggrecan
D. Chondronectin

83
 6. Bone provides a storage site for which
substances?
A. Calcium & Phosphorous
B. Carbon & Phosphate
C. Calcium & Phosphate
D. Calcium & Phosphatase

84
 7. Which is true of calcitonin?

A. Not involved in regulating blood calcium levels

B. Inhibits osteoclast formation
C. Secreted by the parathyroid gland
D. Regulates bone remodeling before closure of the epiphyseal plates

85
8. Which is the uncalcified bone matrix which is
mineralised by osteoblasts?
A. Osteoid
B. Osteocalcin
C. Osteonectin
D. Osteopontin

86
9. What is the prerequisite for osteoprogenitor
cells to differentiate into chondrogenic cells?
A. Bone fractures
B. Stimulation by Parathyroid hormone
C. Closure of the epiphyseal plates
D. Low oxygen tension

87
10. What represents the areas of bone resorption?

A. Trabeculae
B. Howship Lacunae
C. Lamellae
D. Haversian Canals

88