Chapter 3&4
Cartilage and Bone
Qiong Liu M.D, Ph. D
刘琼
Assoc. Prof.
Department of Human Anatomy, Histology and Embryology
Shanghai Medical College
Fudan University
liuqiong@fudan.edu.cn
Chapter 3. Cartilage
• Widely distributed; e.g. trachea, joints and
junction between sternum and ribs etc
• Main function: support, shock-absorbing,
joint movement, temporary skeleton in
embryo, model for long bone development
• Resilient: able to withstand compression
• Avascular: no vessels, nutrients diffused from
the blood supply in perichondrium
• Slow in repair in case of damage
Cartilage
• Embryo
– More prevalent than in
adult
– Skeleton initially mostly
cartilage
– Bone replaces cartilage in
fetal and childhood
periods
Location of cartilage in adults
• External ear
• Nose
• “Articular” – covering the
ends of most bones and
movable joints
• “Costal” – connecting ribs
to sternum
• Larynx - voice box
• Epiglottis – flap keeping
food out of lungs
• Cartilaginous rings
holding open the air tubes
of the respiratory system
(trachea and bronchi)
• Intervertebral discs
• Pubic symphysis
• Articular discs such as
meniscus in knee joint
(1) Form a framework supporting soft tissue.
(2) Located in the area for joint.
(3) Essetial for the development of long bone.
Common Structure
cells→chondrocytes (only cell type)
Cartilage tissue
(no blood vessels)
produce
collagen/elastin
extracellular
matrix
(cartilage matrix) ground substance
Inner layer: rich in osteoprogenitor cells
Perichondrium
(dense C.T.)
Out layer: rich in collagen fibers
•Cartilage tissue has no blood vessels,
the nutrients are supplied by diffusing from the perichondrium.
•Exception (no perichondrium) : articular cartilage
Three types of cartilage
1. Hyaline cartilage: flexible and
resilient
–
–
–
•
Elastic cartilage: highly bendable
1.
2.
•
Chondrocytes appear spherical
Lacuna – cavity in matrix holding
chondrocyte
Collagen the only fiber
Matrix with elastic as well as collagen
fibers
Epiglottis, larynx and outer ear
Fibrocartilage: resists compression
and tension
–
–
Rows of thick collagen fibers
alternating with rows of chondrocytes
(in matrix)
Knee menisci and intervertebral discs
Hyaline cartilage
• Characterized by its homogenous glassy matrix
• With sparsely distributed cells embedded in matrix
• These cells, known as chondrocytes, oval in shape, each is
surrounded by a space, lacuna
• Often several chondrocytes may be seen forming small
aggregates, isogenous groups, representing chondrocytes
that have recently divided.
• Secretion of new matrix in isogenous group gradually push
these cells apart, resulting in interstitial growth
• The periphery of cartilage is surrounded by perichondrium
• Cells in perichondrium are known as chondroblasts
• Conversion of chondroblasts to chondrocytes by secreting
matrix, resulting in appositional growth
Chondrocytes
• only cell type, embedded in the matrix
• LM
variety in size and shape
periphery area: flat and small, immature
center area: round and big, mature
cytoplasm: weakly basophilic
nucleus: eccentrically-located
• EM
rich in RER, Golgi complex
Chondrocytes
(e.g. trachea):
• Synthesize the matrix
• Fill the lacunae
completely
• Typical of protein
secretory cells (elaborate
RER, well-developed
Golgi complex
• Exist in isogenous groups
Growth
 Interstitial growth
In the center of cartilage tissue, mitotic division of pre-existing
chondrocytes results in the expansion of cartilage from inside.
• In early phase of cartilage formation of fetus.
• Epiphyseal plate of long bone (responsible for the longitudinal growth).
• Articular cartilage (no perichondrium).
Appositional growth
The osteoprogenitor cells in the inner
layer of perichondrium proliferate and
transformed into chondrocytes.
• In cartilage found elsewhere in the body.
Ground substance
proteins
 proteoglycans
*
hyaluronic acid
chondroitin sulfate
karatin sulfate
glycosaminoglycans (GAGs)
 glycoproteins:
chondronectin
Bind to GAGs, collagen and integrins
 water
adherence of chondrocyte to
the cartilage matrix
Elastic cartilage
• Epiglottis, ear auricle, walls of the external
auditory canals, auditory tubes
• Avascular
• Abundant network of elastic fibers in
addition to collagen type II
• Possesses a perichondrium
Elastic cartilage
Chondrocytes
Elastic fibres in
matrix
Perichondrium
Fibrocartilage
• In intervertebral disks, initial segment of
ligament attaching to surface of bone,
symphysis pubis
• Characteristics, intermediate between dense
connective tissue and hyaline cartilage
• Chondrocytes often arranged in rows between
bundles of collagen fibers
• Developed from pre-existing fibrous connective
tissue, thus contain type I collagen (preexisting) as well as type II collagen (by
chondrocytes)
• No identifiable perichondrium
Fibrocartilage
Dense collagen matrix
Chondrocyte in lacuna
Chapter 4. Bone
•
•
•
•
One of the hardest tissue in the body
Second to cartilage in withstanding stress
Support and protection
For muscle attachment: locomotion and
movement of limbs
• Reservoir of calcium and phosphate
– Both can be mobilized from bone matrix as needed to
maintain appropriate levels in body
– Regulated through hormones, i.e. parathyroid hormone
and calcitonin
• Harbours the bone marrow, blood forming
site
Structure
Bone
tissue
Osteoprogenitor cell
cells Osteoblast
produce
Osteocyte
ground substance
Osteoclast
Organic matter
bone matrix (25% of bone weight) collagen fibers (90%)
(Bone lamellae)
(plywood-like)
Periosteum
Inorganic matter: hydroxyapatite crystal
(75% of bone weight)
Ca10(PO4)6(OH)2
Inner layer: rich in osteoprogenitor cells
Out layer: rich in collagenous fibers
Endoosteum: rich in osteoprogenitor cells
Bone marrow
Bone cells
• Osteoblasts
– Located over the surface of bone; periosteum and
endosteum
– Strongly basophilic cytoplasm with well developed
RER
– Active in synthesis and secretion of collagen and
bone matrix, mineralization of bone matrix
– Able to undergo cell division and differentiate to
osteocytes, maintain contact through gap junctions
– Role in bone repair
• Osteocytes
– Cells entrapped in bone matrix with long processes
of cytoplasm making contact with adjacent cells in
canaliculi, communicate through gap junctions
– Active in secretion bone matrix and maintenance
– Unable to undergo cell division
– Nourished by diffusion through canaliculi
• Osteoclasts
– Found in sites of bone resorption and remodelling
– Large cells with multiple number of nuclei,
cytoplasm with numerous lysosomes
– With specialized ruffled borders characterized by
extensively folded membrane
– Derived from monocytes by fusion
Osteoprogenitor cell
 Stem cells
 Situation:
endosteum
inner layer of the periosteum
• Structure
small and flat or spindle
nucleus: ovoid
cytoplasm: unremarkble
• differentiate into both
chondroblast & osteoblasts
• arranged as simple cuboidal
epithelial layer on the surface
of bone tissue
• LM: cuboidal/columner
Nucleus: large, round
Cytoplasm: basophilic
• EM: RER and Golgi complex
• synthesize and secrete organic
components (osteoid) and
mediate its mineralization
• embed themselves into the
bone matrix, and then
transform into the osteocytes
Osteoblast
Osteoid
Golgi
EMgraph of
osteoblast
Osteoblast synthesizes
and secretes the
prebone (osteoid)
which is subsequently
mineralized (calcified)
to form bone. Note the
well developed RER
and Golgi of osteoblast.
Osteoblast also secretes
matrix vesicles (50200nm) to osteoid
crucial to initiation of
mineralization of bone.
Osteoblasts and Mineralization
• In addition to secretion of organic matrix of bone, including
collagen, proteoglycans, glycoproteins, osteonectin,
osteopontin and osteocalcin, they also play crucial role in the
processes of mineralization (calcification)
• At appropriate time, osteoblasts secrete membrane-bound
matrix vesicles to bone matrix (osteoid)
• These vesicles contain alkaline phosphatase and
pyrophosphatase which are important in regulating the initial
site of mineral deposition in osteoid
• Once the initial crystals of hydroxyapatite have been formed
at a matrix vesicle, they grow rapidly until they join
neighbouring crystals from other matrix vesicles and
eventually throughout the osteoid
Osteocyte
• the principal cells, located both within
and between the bone lamellae.
• Terminally differentiated bone cell
• LM: Flattened cell with long processes,
weakly basophilic plasma, darkly
stained nucleus.
• EM: rich in RER and Golgi complex.
Osteoclast
• derived from fusion of monocytes
• large and irregularly shaped,
multinucleated (2-50 per cell),
acidophilic cytoplasm
•
numerous mitochondria and lysosomes
in the cytoplasm
• Form ruffled border on the surface facing
bone matrix
• Clear zone: a site of adheion of osteoclast
to bone matrix, surrounding the ruffled
border, devoid of organelles, yet rich in
microfilament.
• secrete acid, collagenase and other lytic
enzymes into a microenvironment, break
down bone matrix.
resorption bays
EMgraph of
osteoclast
Ruffled border of an
osteoclast (characterized by
extensively folded
membrane) facing the
resorption surface of bone
Ruffled
border
Bone matrix
Inorganic:
• Calcified, 50% of dry weight; bone rigidity, primarily
hydroxyapatite crystals: Ca10(PO4)6(OH)2
Organic:
• Fibrous component (collagen type I) arranged in
lamellae
• Fibrils of adjacent lamellae are arranged at right
angles to each other; allows flexibility and to withstand
stress
• Proteoglycans and glycoprotein; e.g. osteonectin: binds
calcium; osteopontin: attachment of cell to matrix;
osteocalcin: capture calcium to stimulate osteoblasts in
bone remodelling etc
*bone lamella: bone matrix arranged in layers at different direction
Periosteum
• Layer of connective tissue closely adheres to bone
surface
• Containing osteoprogenitor cells which form the
inner most layer of periosteum on the bone surface
• They differentiate to osteoblasts; these are more
cuboidal basophilic cells actively involve in bone
matrix secretion
• Form the outer circumferential lamellae
• Vascularized, provide blood supply to bone tissue
• Closely adhere to bone surface through course
collagen bundles (perforating fibers (Sharpey’s
fibers)) embedded in bone matrix
Endosteum
• Similar to periosteum
• Thinner
• Lined mainly by osteoblasts separating the
bone surface from bone marrow
• Form inner circumferential lamellae
• No perforating fibers (Sharpey’s fibers)
Types of bone
(by gross obversation)
• Cancellous ( Spongy) bone
– Spongy, found in head of long bone
– Immature (woven) bone, collagen fibrils more
randomly arranged, can be converted to mature bone
– No Haversian system, not necessary
• Compact bone
– Lamellar bone, as the bone matrix is organized in
lamellae, fibrils in adjacent lamellae are arranged at
right angles to each other
– Vascular in nature, provided through vessels in
Haversian and Volkmann’s canals
– Bone matrix organized in Haversian systems (osteons),
consisting of concentric layers of matrix lamellae
– Shaft (diaphysis) of long bone
Spongy bone
Bone marrow
Bony trabeculae
of spongy bone
Architecture of diaphysis of a long bone
(compact bone)
three patterns:
• Circumferential lamella
external circumferential lamellae
inner circumferential lamellae
• Haversian system (osteon)
Haversian canal (central canal)
Haversian lamellae
• Interstitial lamella
triangular or irregular
(left by old osteon)
Perforating canals （Volkmanns canals): the transverse canal connecting
with central canal
Cross-section of compact bone (ground)
---Circumferential lamella
---Osteon (outlined by a cement line)
---Interstitial lamella
Haversian system (osteon)
• Structural unit of compact bone, also known as osteon
• Characterized by having several concentric layers of bony
lamellae as well as osteocytes arranged around a central canal,
the Haversian canal, thus Haversian system
• Osteocytes are connected through a system of canaliculi, tiny
canals, existing within the bony matrix; they communicate with
each other through gap junctions
• Collagen fibrils in adjacent bony lamellae are arranged at right
angles to each other
• The outer most lamella is surrounded by a cementing line to
mark the outer limit of the osteon
• The canal is lined by osteoblasts; contains some connective
tissue, blood vessels and nerves
• Nutrients diffuse from vessels through canaliculi to reach
osteocytes within the osteon
Haversian system (osteon) /Harversian canal
HC
HC
Osteogenesis of bone
(bone formation)
Two manners of ossification：
intramembranous ossification
- Only a few bones form in this way (frontal and parietal
bones of the skull, the mandibal and the maxilla).
endochondral ossification
-before ossification, firstly form a cartilage model and then a
continuously growing which is progressively replaced by bone
Comparison of two forms of ossification
Intramembranous
ossification:
Endochondral
ossification:
• Important for formation of
flat bones
• Condensation of
mesenchymal tissues into
membranous structure
• Differentiation of
mesenchymal cells into bone
forming cells (osteoblasts)
• Flat bones of skull, mandible
• No cartilage model involved
• Development of a
cartilagenous model
• Gradually replacing the
cartilagenous model by
bony material
• Development of long and
short bones
• Important for elongation
(growth) of long bone
• Through epiphyseal
growth plate
Processes of intramembranous
ossification
•
•
•
•
•
Groups of mesenchymal cells directly differentiate
into osteoblasts
New bone matrix is synthesized and mineralized by
osteoblasts
Osteoblasts become entrapped in matrix to become
osteocytes
Surrounding connective tissue becomes the
periosteum (inner layer - osteogenic) of the newly
formed bone
Replacement of the newly formed immature bones
(primary) to form mature (secondary) bones
Endochondral ossification
• Development of long and short bones, bones of the
limbs
• Formation of a hyaline cartilage model
• Growth of cartilage model
• Gradually replacing the cartilage model with bony
structure in an orderly stepwise manner
• Often begins at diaphyseal center (primary ossification centre)
• Later to epiphyseal centre (secondary ossification centre)
• Formation of epiphyseal growth plate, between the two
centres
• Responsible for further growth of long bones
• Regulated by growth hormone
Growth in Length
40
Growth in Length
zone of ossification
osteoblast
primary bone marrow cavity
osteoblast
osteoclast
primary bone trabecula
41
Growth in width

Thickening of the shaft
• Circumferential dposition of bone beneath the periosteum
• Formation of the new haversian system added peripherally to the diaphysis

Enlargement of the marrow cavity
• Resorption of bone on inner surface of marrow cavity.
First(red) / second(purple) / third(brown)-generation haversian system
Bone remodeling
• Osteoclasts
– Bone resorption
• Osteoblasts
– Bone deposition
• Triggers
– Hormonal: parathyroid hormone
– Mechanical stress
• Osteocytes are transformed osteoblasts
Growth & remodeling of long bone
birth
adult
Formation:
osteoprogenitor cell→ osteoblast → osteoid
calcification
osteocyte + bone matrix
formation
bone tissue
dissolution
Dissolution & absorption:
osteoclast
remodeling
Factors influencing bone growth
 Nutritional factors
Vitamin C (collagen
synthesis), Vitamin D (aids
intestinal absorption
(
(
of calcium and reduce renal calcium excretion), Protein and Minerals.
 Hormones
• Growth hormone: growth of epiphyseal cartilage.
• Calcitonin
• Parathyroid hormone