Cartilage and Bone Development and Growth
Cartilage and bone are specialized forms of connective tissue derived from embryonic
Both consist of cells embedded in an extracellular matrix
Cartilage matrix is highly hydrated, being 70 – 75% water. The rest of the matrix is
composed of collagen (15 – 20%), for tensile strength, and proteoglycans (2 – 10%) for
resistance. It is avascular and has no nerve or lymphatic supply.
Bone is the calcified component of the skeleton. The matrix of bone consists of collagen
embedded in a ground substance on which is deposited a complex inorganic mineral,
hydroxyapatite. Compared with cartilage, bone has a higher metabolic rate, is richly
vascularized, and receives up to 10% of cardiac output.
Bone has good regenerative potential for self-repair throughout life, whereas cartilage
has a very limited capacity for regeneration in response to traumatic injury or disease.
Bone develops with or without a cartilage intermediate
Via cartilage model
Without cartilage intermediate
Intramembranous (mesenchymal) ossification
The transcription factors Sox9 (chondroblasts), Cbfa1/Runx2 and Osterix (osteoblasts)
play critical roles in the development of the skeleton – cartilage and bone
Chondroblasts (cartilage) and osteoblasts (bone) derive from pluripotent
mesenchymal cells when appropriate transcription factors are expressed
Interstitional – lower, in hyaline matrix
Hyaline – type II collagen
Elastic (arteries) – type II collagen + elastin
Fibro (tensile strength) – type I collagen Bone Development: Endochondral Ossification
Cartilage – future bone. Entirely covered by a delicate perichondrium
A thin collar of bone has formed around the diaphysis
Vascularization of the bone collar and hypertrophy of the diaphyseal chondrocytes –
called the primary ossification center
Blood vessels enter the newly formed medullary cavity and grow toward the epiphyseal
ends of the bone, establishing the two epiphyseal growth plates
A secondary center of ossification has formed, and the whole bone has elongated owing
to chondrocyte proliferation and hypertrophy in the growth plate. Up to this time, the
entire developing bone is covered by a perichondrium (where cartilage remains) or a
periosteum (where bone has formed).
Further lengthening of the bone, appearance of a second center of secondary
ossification, and further development of bone vasculature. The cartilage-covered
articular surfaces no longer have a perichondrium.
An adult bone – the cortical bone has thickened, the bone has achieved its full length
and width, the epiphyseal plate have become ossified (“closed”) – epiphyseal line, and
the articular surfaces are free of a perichondrium.
Mutations in genes encoding chondrogenic/osteogenic transcription factors are the genetic
basis of skeletal disorders
Mutations in the Sox9 gene cause the rare and severe dwarfism – Campomelic
Sox9-null chondrogenic cells remain in perichondrium and do not differentiate
Cbfa1/Runx2 – deficient mice have a skeleton consisting of cartilage without any
indication of osteoblast differentiation represented by bone formation and mineralization.
In addition, because osteoblasts regulate the formation of osteoclasts, Cbfa1/Runx2 –
deficient mice lack osteoclasts.
Patients with cleidocranial dysplasia (hypoplastic clavicles and delayed ossification of
sutures of certain skull bones) have a Cbfa1/Runx2 type of gene mutation
A total lack of expression of the Cbfa1/Runx2 gene determines that the entire
skeleton consists only of cartilage
An autosomal dominant skeletal dysplasia characterized by abnormal clavicles,
patent sutures and fontanelles, supernumerary teeth, short stature, and a variety
of other skeletal changes. Bone Development: Intramembranous Ossification
Mesenchymal cells differentiate directly into osteoblasts and form bone without a
Mesenchymal cells aggregate without a cartilage intermediate. This process is
controlled by patterning signals from polypeptides of the Wnt, hedgehog, fibroblast
growth factor, and transforming growth factor-β families.
Mesenchymal cells differentiate into osteoblasts. A bone blastema is formed.
Osteocytes within the core of the blastema are interconnected by cell processes forming
a functional syncytium. Osteoblasts line the surface of the bone blastema.
Bone matrix (osteoid) is deposited by osteoblasts. Later, Ca , transported by blood
vessels, is used in the mineralization process and primary bone tissue is formed.
Osteoclasts initiate the modeling of the bone tissue.
Organization of a primary ossification center
Multiple individual trabeculae enlarge by appositional growth and eventually fuse
together as a primary ossification center organized during the first stage of
Although primary bone tissue formation begins as an interstitial process, it soon
Osteocytes become trapped within the calcified osteoid.
At the surface of the osteoid, osteoblasts continue the appositional deposit of
matrix, mainly type I collagen and noncollagenous proteins.
Several members of the Bone Morphogenetic Protein (BMP) family regulate embryonic
development and skeleton formation
Several BMPs are also named ‘cartilage-derived morphogenetic proteins’ (CDMPs),
while others are referred to as ‘growth differentiation factors’ (GDFs). Some of these
belong to the Transforming growth factor-beta (TGF –β) superfamily of proteins.
Mutations in BMPs, their inhibitors, or their receptors are associated with a number of
inherited human disorders which affect the skeleton.
Fibrodysplasia ossificans progressiva
Ectopic ossification is observed as lumps in the muscles of the neck and back.
Lumps are first noted in children 1 to 3 years old.
Ectopic bone is visualized in radiographs after the initial appearance of ossifying
lumps. Bone matures and develops a normal trabecular architecture
An activating mutation in the gene encoding a receptor for a BMP leading to the
transformation of connective tissue and muscle tissue into a secondary skeleton. Muscle Tissue
Histologically, muscle tissue is described as being smooth or striated
Striated is further subdivided into skeletal and cardiac muscle
Since muscle cells are elongated, all three types are called fibers rather than cells
Each individual cell/fiber is invested with a delicate external lamina similar to
Skeletal muscle comprises the major muscle mass of the body and its contraction is
under voluntary control.
Description: Long, striated cells with multiple nuclei
Common locations: In skeletal muscles
Function: Contraction for voluntary movements
Smooth muscle is widely distributed in many organs, where it may have contractile or
supporting functions, or both. Smooth muscle is also found in the walls of all blood
vessels larger than capillaries. It is generally referred to as involuntary muscle, since its
contraction is regulated by the autonomic nervous system. Smooth muscle fibers exhibit
an intrinsic contractility, so they may contract in the absence of external or nervous
stimuli; the peristaltic waves of contraction o