Bone Development Histology Fundamentals > Musculoskeletal System > Musculoskeletal System

BONE DEVELOPMENT: OSTEOGENESIS (OSSIFICATION)&NBSP;

Endochondral ossification

• An INDIRECT form of ossification, wherein a hyaline cartilaginous model (template) is replaced with bone, such as occurs with long bones (eg, the femur).

Intramembranous ossification

• A DIRECT form of ossification mesenchymal cells directly differentiate to osteoblasts (no cartilaginous model is first formed), such as occurs with flat bones (the skull bones).

INTRAMEMBRANOUS OSSIFICATION&NBSP;

• Embryologically, skeletal tissues typically derive from mesoderm: the midline (axial) skeleton derives from the somites and the appendicular (the limb) skeleton derives from the lateral plate.

• Mesenchymal cells migrate to vascularized gelatinous extracellular collagen fiber matrix (a primary spongiosa).

• They differentiate directly into osteoblasts.

• Osteoblasts form bone in a loosely arranged (disorganized), immature initial form of bone, called woven bone.

• Osteoblasts become trapped within their own bony matrix and become osteocytes; these bony matrices are referred to as trabeculae (aka fused spicules).

• Woven bone later matures to form lamellar bone, a much tougher form of bone that constitutes both compact bone and spongy bone.

Compact Bone

• The outer layer: the periosteum.

- Comprises columns of compact bone, called osteons.

- Centrally, within each osteon, lies a longitudinally-oriented canal, the Haversian (aka central) canal.

- Each osteon comprises concentric rings of lamellae.

- Osteocytes are a mature form of osteoblast (the bone-producing cells) within the bony matrix.

- Internal to the compact bone, lies the endosteum, which comprises in inner circumferential lamellae and the

1 / 7 osteoprogenitor cells, internal to it.

Spongy bone* Lies internal to the endosteum and comprises a network of lamellae that do NOT form the Haversian channels and osteons found in compact bone. ENDOCHONDRAL OSSIFICATION

Origins

• Mesenchymal cells migrate and differentiate to form a hyaline cartilage model, which comprises basophilic collagen and ground substance.

• Chondrocytes are part of a cartilaginous model that are hyaline cartilage cells, which are purplish (basophilic).

- Key histological features: their nucleus and lipid droplets.

- Chondrocytes produce the structural components of cartilage: collagen, proteoglycans and glycosaminoglycans, and are usually found in clusters (isogenic groups) of recently divided cells.

- Chondrocytes hypertrophy, which signals (via vascular endothelial cell growth factor) the sprouting of blood vessels, which we'll draw next.

Bone Regions

• The diaphysis (the shaft)

• The epiphyses (the articulating ends of the long bone)

• The metaphyses that separate them.

Periosteal Buds

• Periosteal buds invade the center of the diaphysis. Vascularization occurs via the periosteal bud, which brings forth osteoprogenitor cells and forms the primary ossification center, which forms within the cavities that are created when the hypertrophic chondrocytes starve and apoptose (die).

• Vasculature further invades the primary ossification center and the osteoprogenitor cells remodel bony matrix as the ossification center grows linearly (via interstitial growth).

• The outer cartilage is perichondrium, which forms a periosteal bone collar of compact bone that grows in opposite orientation, increasing the bone thickness (via appositional growth) – here, the osteoblasts secrete bone matrix directly via intramembranous ossification. Periosteum distributes blood vessels to bone and is not found in synovial articulations or muscle attachment sites.

Medullary cavity

• Forms as the primary ossification center degenerates cavitates and remodels via interstitial growth.

• Endochondrium delineates it, which forms a layer of lamellar bone and osteoprogenitor cells.

• The marrow cavity is filled with hematopoetic marrow (which comprises red and white blood cell precursors)

2 / 7 • Vasculature invades the cavity to fill it with marrow.

Secondary ossification centers.

• Unlike the primary ossification center, they never grow large enough to create marrow cavities but instead remain constituted with spongy bone.

Bone Growth

• Further appositional growth (widening) of the periosteal bone collar occurs along the diaphysis (again which forms compact bone via intramembranous ossification).

• There is an epiphyseal (growth) plate at the border of the metaphysis and the epiphysis: elsewhere we learn about the zones and processes of interstitial growth, but pay attention that Indian hedgehog (Ihh) was discovered to be important for the stimulation of chondrocyte growth with delay of chondrocyte hypertrophy (thus delaying a key step in endochondral ossification).

MAJOR BONES & THEIR DEVELOPMENT

Intramembranous Ossification

• Cranial Vault

• Maxilla/Mandible

• Clavicles

Consider that the skull bones must ossify prior to delivery of the fetus, so the brain isn't squashed during childbirth to help us remember that intramembranous ossification is a more direct form of ossification.

Endochondral ossification

• Skull base

• Vertebrae

• Pelvis

• Long Bones

They grow extensively throughout pediatric development and require an amount of pliability via their cartilaginous template prior to committing to ossification too soon. Consider that for a time-period, children fall often and thus must bounce and not break!

Clinical Correlations

• Bone Fracture & Repair

• Skeletal Dysplasias

3 / 7 FULL-LENGTH TEXT

• Here, let's addresses the two major processes of bone development.

• Start a table.

• Denote that bone formation is called osteogenesis (ossification).

- Start with the most common form: endochondral ossification — which we learn is an INDIRECT form of ossification, wherein a hyaline cartilaginous model (template) is replaced with bone, such as occurs with long bones (eg, the femur).

- Next, denote that in intramembranous ossification — which we learn is a DIRECT form of ossification mesenchymal cells directly differentiate to osteoblasts (no cartilaginous model is first formed), such as occurs with flat bones (the skull bones).

Begin with intramembranous ossification.

• First, draw a plate of mesoderm – remember that embryologically, skeletal tissues typically derive from mesoderm: the midline (axial) skeleton derives from the somites and the appendicular (the limb) skeleton derives from the lateral plate.

• Now, draw a vascularized gelatinous extracellular collagen fiber matrix (a primary spongiosa) and show that mesenchymal cells migrate to these collagenous center and differentiate directly into osteoblasts.

• Then, show that osteoblasts form bone in a loosely arranged (disorganized), immature initial form of bone, called woven bone.

• Next, show that osteoblasts become trapped within their own bony matrix and become osteocytes; these bony matrices are referred to as trabeculae (aka fused spicules).

• Show that woven bone later matures to form lamellar bone, a much tougher form of bone that constitutes both compact bone and spongy bone in different fashions as follows:

Begin with the outer layer of a bone: the periosteum.

• Internal to it, draw a column of compact bone, called an osteon.

• Show that centrally, within the osteon, lies a longitudinally-oriented canal, the Haversian (aka central) canal.

4 / 7 • Show that the osteon comprises concentric rings of lamellae.

• Then, indicate an osteocyte (a mature form of osteoblast (the bone-producing cells) within the bony matrix.

• Now, internal to the compact bone, draw the endosteum, which comprises in inner circumferential lamellar system and osteoprogenitor cells, internal to it.

• Show that spongy bone lies internal to the endosteum and comprises a network of lamellae that do NOT form the Haversian channels and osteons found in compact bone.

Next, let's draw endochondral ossification.

• First, show that mesenchymal cells migrate and differentiate to form a hyaline cartilage model, which comprises basophilic collagen and ground substance.

• Draw a couple of representative purplish (basophilic) chondrocytes, which are hyaline cartilage cells.

Indicate key histological features: their nucleus and lipid droplets.

- Chondrocytes produce the structural components of cartilage: collagen, proteoglycans and glycosaminoglycans, and are usually found in clusters (isogenic groups) of recently divided cells.

• Then, show that the chondrocytes hypertrophy, which signals (via vascular endothelial cell growth factor) the sprouting of blood vessels, which we'll draw next.

• Redraw the cartilaginous model.

• In the center, draw vascularization via the periosteal bud, which brings forth osteoprogenitor cells.

• Indicate that they form the primary ossification center, which forms within the cavities that are created when the hypertrophic chondrocytes starve and apoptose (die).

• Show that vasculature further invades the primary ossification center and the osteoprogenitor cells remodel bony matrix as the ossification center grows linearly (via interstitial growth).

• Indicate that the outer cartilage is perichondrium, which forms a periosteal bone collar of compact bone that grows in

5 / 7 opposite orientation, increasing the bone thickness (via appositional growth) – here, the osteoblasts secrete osteoid directly via intramembranous ossification.

• Periosteum distributes blood vessels to bone and is not found in synovial articulations or muscle attachment sites.

• Now, redraw the cartilaginous model, again.

• Delineate the diaphysis (the shaft) and the epiphyses (the articulating ends of the long bone) and the metaphyses that separate them.

• In the center, draw the medullary cavity, which forms as the primary ossification center degenerates cavitates and remodels via interstitial growth.

• Indicate that endochondrium delineates it – which forms a layer of lamellar bone and osteoprogenitor cells.

• Then, show that the marrow cavity is filled with hematopoetic marrow (which comprises red and white blood cell precursors)

• Remind ourselves of the vasculature, which invades the cavity to fill it with marrow.

• Now, at the epiphyses, draw secondary ossification centers.

• Unlike the primary ossification center, they never grow large enough to create marrow cavities but instead remain constituted with spongy bone.

• Now, show further appositional growth (widening) of the periosteal bone collar along the diaphysis (again which forms compact bone via intramembranous ossification).

• Next, show the epiphyseal (growth) plate at the border of the metaphysis and the epiphysis: elsewhere we learn about the zones and processes of interstitial growth, but pay attention that Indian hedgehog (Ihh) was discovered to be important for the stimulation of chondrocyte growth with delay of chondrocyte hypertrophy (thus delaying a key step in endochondral ossification).

Now, let's consider, which major bones form via which process.

• Indicate that the cranial vault, maxilla/mandible, and clavicles all form via intramembranous ossification – consider that

6 / 7 the skull bones must ossify prior to delivery of the fetus, so the brain isn't squashed during childbirth to help us remember that intramembranous ossification is a more direct form of ossification.

• Indicate that the skull base, vertebrae, pelvis, and long bones all undergo endochondral ossification – they grow extensively throughout pediatric development and require an amount of pliability via their cartilaginous template prior to committing to ossification too soon.

- Consider that for a time period, children fall often and thus must bounce and not break!