Cartilage and Bone

Fayez F. Safadi, Ph.D.

Musculoskeletal Biology Course

 Cartilage and Bone
Extracellular Matrices
Consistency Composition
Cartilage Gel Organic:
40% Collagen type II
60% Proteoglycans

Bone Rigid Organic (50%):

95% collagen type I
5% other (GAG)
Inorganic (50%):
Ca-PO4 crystals
Cartilage is a specialized connective tissue

Support
Embryonic skeleton, airways

Shock absorption, resisting compression

Intervertibral disc, meniscus

Smooth sliding surface

Joints

Framework
Development and growth of bone
Cartilage: ExtraCellular Matrix

Proteins
Collagen type II - Major protein of cartilage ECM
Collagen type IX - crosslinks fibrils of type II
Collagen type X - epiphyseal plate of long bones

Collagen type I - in Fibrocartilage

Elastin - in Elastic cartilage

Proteoglycan aggregates
Cartilage: ExtraCellular Matrix

Proteins
Collagen type II - Major protein of cartilage ECM
Collagen type IX - crosslinks fibrils of type II
Collagen type X - epiphyseal plate of long bones

Collagen type I - in Fibrocartilage

Elastin - in Elastic cartilage

Proteoglycan aggregates
Chondrocyte Lineage
Cartilage Growth
Chondrocyte-Structure
Chondrocyte

Territorial
matrix
Cartilage types

Hyaline cartilage
Ribs, trachea, larynx, articular cartilage

Fibrocartilage cartilage (contains collagen type I)

Intervertebral disc, pubic symphisis
Attachment of tendons, meniscus

Elastic cartilage (contains elastic fibers)

External ear, auditory canal
Epiglottis
Hyaline Cartilage

Trachea
 Hyaline Cartilage
Growth:
Appositional and
interstitial
Fibers: Type II
collagen
Interstitial Appositional
Growth Growth
 Elastic Cartilage

Chondrocytes

Perichondrium
 Elastic Cartilage

Elastic fibers
Growth: Appositional
and interstitial
Fibers: Type II collagen,
elastic fibers
 Fibrocartilage

Growth: Interstitial
Fibers: Type I collagen
Fibrocartilage
Cartilage types

Articular cartilage (a form of Hyaline)

Cover all surfaces of bone in joints

NO perichondrium

Enclosed by synovial membrane

specialized fibroblasts

Synovial fluid
Hyaluronic acid
Rich in nutrients
Articular cartilage
Differentiating chondrocytes Hypertrophic chondrocytes
Cartilage is AVASCULAR

Nutrients must diffuse through ECM

Limits cartilage growth and repair

This is an ACTIVE process

Factors can be isolated from cartilage that retard
angiogenesis in experimental systems
Cartilage

Cells
Chondroblasts
Chondrocytes

ExtraCellularMatrix
Proteins
Collagen types II, IX

Proteoglycan aggregates
Backbone of hyaluronic acid
Core protein linked to hyaluronic acid
Keratan and chondroitin sulfate on core proteins

H20
 Chondrogenesis in vitro

(Wnt)

Mature
chondrocytes

Undifferentiated
mesenchymal
cells
 Experimental Analysis of Chondrogenesis in Vitro:

Control

+Wnt
protein

Alcian Blue Alcian Blue + Hematoxylin

(stains cartilage matrix)
Cartilage Diseases
Rheumatoid Arthritis
Inflammatory joint disease, or as a result of an
autoimmune reaction
Cartilage Diseases
Rheumatoid Arthritis

Panus
 Chondrocytes and Genetics
The transcription factor, Sox9 is required for the
expression of cartilage-specific ECM (collagen
type II).
Lack of Sox9 expression prevents the
chondrogenic layer to differentiate into
chondrocytes.
Bone
Bone Composition
Cortical Bone
 Bone

Ground bone

De-calcified
bone
SEM
Trabecular (cancellous, spongy) Bone

Bony trabeculae

Bony trabeculae
Periosteum
Endosteum
Collagen
Bone marrow
Bone Cells: Osteoblasts
 Bone Cells: Osteoblasts

Osteoprogenitor cells
Osteoblasts
Bone matrix
Osteoid
 Bone Cells: Osteoclasts

Osteoclasts
Osteoblasts
Bone matrix
Osteoid
Bone Cells: Osteoclasts
Biology of Bone Resorption
Osteoclasts
 Bone Cells: Osteocytes

Haversian system
Osteocytes
Canaliculi
Bone Cells: Osteocytes
KEVIN J CRAWFORD <tuc15636@temple.edu>

From Dr. Fuortes

 2

3 2

1 3
1
4
5
Name the areas indicated by the numbers

1: Osteoclasts 3:Osteocytes
5:Fibrous layer
2: Osteoblasts 4:Cellular layer
Review; OB, OC and OS
 Regulation of Osteoclast Differentiation by Osteoblasts
M-CSF:
Macrophages colony
stimulating factor

RANK:
Receptor for activation
of nuclear factor kappa B

RANKL: Receptor
for activation of nuclear
factor kappa B ligand
 Calcium Homeostasis

1,25(OH)2D3 Ca++

PTH Ca++
Hypercalcemia

Calcitonin Ca++

Hypocalcemia
Bone Diseases Rickets/Osteomalacia
Inadequate Mineralization
* Defective vitamin D intake or metabolism.
* Defective mineralization of osteoid.
* Increased osteoid thickness.
* Treatment by vitamin D supplement.
Normal Osteomalacia
Bone Diseases
Osteoporosis (Bone loss)
Uncoupling of Bone Formation and Resorption
* Factors: Aging, Post-menopausal, Disuse,
Inflammation and Diabetes.

Disuse Osteoporosis
Bone Diseases
Osteoporosis (Bone loss)

General Osteoporosis

Normal bone Osteoporotic bone

Normal Bone Osteoporotic Bone
Bone Diseases Osteopetrosis
Increase bone mass
* Defective bone resorption.
* Failure development of bone marrow.
* Splenomegaly.
* Thrombocytopenia.
Bone Diseases Cleidocranial Dysplasia (CCD)

Cleidocranial Dysplasia (cleido = collar bone, cranial = head,

dysplasia = abnormal forming)

* CCD is an autosomal dominant skeletal dysplasia.

* Caused by different mutations in the cbfa-1 (Runx-2) gene

(DNA binding domain) on chromosome 6.

* cbfa-1 (core biding factor a-1), osteoblast-specific

transcription factor.

* CCD characterized by defective development of the

cranial bones and by the complete or partial absence of the
collar bones (clavicles).
Bone Diseases Cleidocranial Dysplasia (CCD)
 Bone Diseases
Cleidocranial Dysplasia (CCD)

* Characteristics include:
Delayed closure
(ossification) of the space
between the bones of the
skull.
* Short stature
* Scoliosis of the spine
* Teeth abnormalities
Bone Diseases Cleidocranial Dysplasia (CCD)

Cbfa1 knockout mice showed:

* Skeleton consisting of
cartilage only.

* No bone formation nor

mineralization.

* No osteoblasts

* No osteoclasts
Bone Diseases
Fibrodysplasia Ossificans Progressiva (FOP)
A rare autosomal dominant genetic disorder of ectopic
bone formation.

Most cases are sporadic.

Few examples of inheritance within a family.
The mutated gene is unknown.
Progressive endochondral ossification in skeletal
muscle, tendon and ligament.
Bone Diseases Fibrodysplasia Ossificans Progressiva (FOP)
Bone Diseases
Fibrodysplasia Ossificans Progressiva (FOP)
Bone Diseases
Fibrodysplasia Ossificans Progressiva (FOP)