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ENDOCHONDRAL
BONE FORMATION
-Numa Sarang
First Year BDS
BONE FORMATION
Endochondral Bone Formation
 Intracartilaginous (Endochondral)
Bone Formation is a type of
ossification that involves the
replacement of a cartilaginous model
by bone, and occurs at the extremities
of all long bones, vertebrae, ribs,
articular extremity of the mandible
and base of the skull.
 The process involves the following
steps:
STEPS INVOLVED:
1. FORMATION OF CARTILAGINOUS MODEL
2. GROWTH OF CARTILAGINOUS MODEL
3. FORMATION OF PERIOSTEUM
4. FORMATION OF BONE COLLAR
5. CALCIFICATION OF MATRIX
6. FORMATION OF PERIOSTEAL BUD
7. FORMATION OF MIXED SPICULE
8. FORMATION OF MEDULLARY CAVITY
9. FORMATION OF SECONDARY OSSIFICATION
CENTER
DEVELOPMENT OF CARTILAGE MODEL
DEVELOPMENT OF CARTILAGE MODEL
 The mesenchymal cells in condense,
differentiate into chondroblasts and form
the cartilage matrix, resulting in the
development of a hyaline cartilage
model.
 This process begins late in the second
month of development of embryo.
 The model is surrounded by a
perichondrium, made up of an inner
chondrogenic layer and an outer fibrous
layer.
GROWTH OF CARTILAGE MODEL
 The growth of the cartilage model is by
interstitial and appositional growth.
 Increase in the length is by interstitial
growth due to repeated division of
chondrocytes.
 Widening of the model is due to further
addition of matrix to its periphery by
new chondroblasts, derived from the
chondrogenic layer of the
perichondrium. This is called
appositional growth
GROWTH OF CARTILAGE MODEL
 The cells organize into longitudinal columns which are
subdivided into fourzones:
1. Zone of resting cartilage: It is nearest to epiphysis and
chondrocytes anchor epiphyseal plate to bone epiphysis.
2. Zone of proliferation. The cells are small and flat, and
constitute a source of new cells.
3. Zone of hypertrophy and maturation. This is the broadest
zone. The chondrocytes hypertrophy, and in the early stages
secrete type II collagen. As hypertrophy proceeds,
proteoglycans are secreted. The increased cell size and
increased cell secretion lead to an increase in the size of
the cartilaginous model. As the chondrocytes reach
maximum size, they secrete type X collagen and
noncollagenous proteins. Subsequently, there is partial
breakdown of proteoglycans, creating a matrix environment
receptive for mineral deposition.
4. Zone of provisional mineralization. Matrix mineralization
begins in the zone of mineralization by formation of matrix
vesicles. These membrane bound vesicles bud off from the
cell and form independent units in the longitudinal septa of
the cartilage
FORMATION OF BONE COLLAR
 The capillaries grow into the perichondrium that
surrounds midsection of the model.
 The capillaries grow into the perichondrium that
surrounds midsection of the model.
 The cells in the inner layer of the perichondrium
differentiate into osteoblasts in a vascular environment
and form a thin collar of bone matrix around the mid
region of the model.
 At this stage, perichondrium is referred to as periosteum
as the differentiation of cells from the inner layer of the
perichondrium is giving rise to bone.
 Vascularization of the middle of the cartilage occurs,
and chondroclasts resorb most of the mineralized
cartilage matrix.
 Hence, more space is created for vascular ingrowth.
CALCIFICATION OF MATRIX
Chondrocytes grow → secrete alkaline
phosphatase → calcification of matrix →
eventually blood supply cut off → no nutrient
→ death of chondrocytes → cavitation of
cartilage matrix
FORMATION OF PERIOSTEAL BUD
 The osteogenic cells and the vessels
comprise a structure called the periosteal
bud. The periosteal capillaries grow into the
cartilage model and initiate development of a
primary ossification center.
 Osteogenic cells in the periosteal bud give
rise to osteoblasts that deposit bone matrix
on the residual calcified cartilage. This
results in the formation of cancellous bone
that has remnants of calcified cartilage. This
is the mixed spicule. The network of mixed
spicules is called primary spongiosa
FORMATION OF MIXED SPICULE
Osteogenic cells in periosteal bud →
differentiate into osteoblasts →
deposit bone matrix on residual
calcified cartilage.
FORMATION OF PRIMARY OSSIFICATION CENTER
FORMATION OF MEDULLARY CAVITY
 As the primary ossification center enlarges,
osteoclasts break down the newly formed spongy
bone and open up a medullary cavity in the center of
the shaft. Hematopoietic stem cells enter the
medullary cavity giving rise to myeloid tissue (tissue
of bone marrow).
 The two ends of the developing bone are at this stage
still composed entirely of cartilage.
 The midsection of the bone becomes the diaphysis
and the cartilaginous ends of bone become the
epiphysis.
 Hence, the primary center of ossification is the
diaphyseal center of ossification.
FORMATION OF SECONDARY OSSIFICATION CENTER
FORMATION OF SECONDARY OSSIFICATION CENTER
 The epiphyseal plate continues to form new cartilage,
which is replaced by bone, a process that increases
the length of the bone.
 Long bones have one or two secondary ossification
centers.
 Short bones have one ossification center.
 The union of primary and secondary ossification
center is called epiphyseal line.
Endochondral Bone Formation
Endochondral bone formation
Endochondral bone formation
Endochondral bone formation

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Endochondral bone formation

  • 3. Endochondral Bone Formation  Intracartilaginous (Endochondral) Bone Formation is a type of ossification that involves the replacement of a cartilaginous model by bone, and occurs at the extremities of all long bones, vertebrae, ribs, articular extremity of the mandible and base of the skull.  The process involves the following steps:
  • 4. STEPS INVOLVED: 1. FORMATION OF CARTILAGINOUS MODEL 2. GROWTH OF CARTILAGINOUS MODEL 3. FORMATION OF PERIOSTEUM 4. FORMATION OF BONE COLLAR 5. CALCIFICATION OF MATRIX 6. FORMATION OF PERIOSTEAL BUD 7. FORMATION OF MIXED SPICULE 8. FORMATION OF MEDULLARY CAVITY 9. FORMATION OF SECONDARY OSSIFICATION CENTER
  • 6. DEVELOPMENT OF CARTILAGE MODEL  The mesenchymal cells in condense, differentiate into chondroblasts and form the cartilage matrix, resulting in the development of a hyaline cartilage model.  This process begins late in the second month of development of embryo.  The model is surrounded by a perichondrium, made up of an inner chondrogenic layer and an outer fibrous layer.
  • 7. GROWTH OF CARTILAGE MODEL  The growth of the cartilage model is by interstitial and appositional growth.  Increase in the length is by interstitial growth due to repeated division of chondrocytes.  Widening of the model is due to further addition of matrix to its periphery by new chondroblasts, derived from the chondrogenic layer of the perichondrium. This is called appositional growth
  • 8. GROWTH OF CARTILAGE MODEL  The cells organize into longitudinal columns which are subdivided into fourzones: 1. Zone of resting cartilage: It is nearest to epiphysis and chondrocytes anchor epiphyseal plate to bone epiphysis. 2. Zone of proliferation. The cells are small and flat, and constitute a source of new cells. 3. Zone of hypertrophy and maturation. This is the broadest zone. The chondrocytes hypertrophy, and in the early stages secrete type II collagen. As hypertrophy proceeds, proteoglycans are secreted. The increased cell size and increased cell secretion lead to an increase in the size of the cartilaginous model. As the chondrocytes reach maximum size, they secrete type X collagen and noncollagenous proteins. Subsequently, there is partial breakdown of proteoglycans, creating a matrix environment receptive for mineral deposition. 4. Zone of provisional mineralization. Matrix mineralization begins in the zone of mineralization by formation of matrix vesicles. These membrane bound vesicles bud off from the cell and form independent units in the longitudinal septa of the cartilage
  • 9. FORMATION OF BONE COLLAR  The capillaries grow into the perichondrium that surrounds midsection of the model.  The capillaries grow into the perichondrium that surrounds midsection of the model.  The cells in the inner layer of the perichondrium differentiate into osteoblasts in a vascular environment and form a thin collar of bone matrix around the mid region of the model.  At this stage, perichondrium is referred to as periosteum as the differentiation of cells from the inner layer of the perichondrium is giving rise to bone.  Vascularization of the middle of the cartilage occurs, and chondroclasts resorb most of the mineralized cartilage matrix.  Hence, more space is created for vascular ingrowth.
  • 10. CALCIFICATION OF MATRIX Chondrocytes grow → secrete alkaline phosphatase → calcification of matrix → eventually blood supply cut off → no nutrient → death of chondrocytes → cavitation of cartilage matrix
  • 11. FORMATION OF PERIOSTEAL BUD  The osteogenic cells and the vessels comprise a structure called the periosteal bud. The periosteal capillaries grow into the cartilage model and initiate development of a primary ossification center.  Osteogenic cells in the periosteal bud give rise to osteoblasts that deposit bone matrix on the residual calcified cartilage. This results in the formation of cancellous bone that has remnants of calcified cartilage. This is the mixed spicule. The network of mixed spicules is called primary spongiosa
  • 12. FORMATION OF MIXED SPICULE Osteogenic cells in periosteal bud → differentiate into osteoblasts → deposit bone matrix on residual calcified cartilage.
  • 13. FORMATION OF PRIMARY OSSIFICATION CENTER
  • 14. FORMATION OF MEDULLARY CAVITY  As the primary ossification center enlarges, osteoclasts break down the newly formed spongy bone and open up a medullary cavity in the center of the shaft. Hematopoietic stem cells enter the medullary cavity giving rise to myeloid tissue (tissue of bone marrow).  The two ends of the developing bone are at this stage still composed entirely of cartilage.  The midsection of the bone becomes the diaphysis and the cartilaginous ends of bone become the epiphysis.  Hence, the primary center of ossification is the diaphyseal center of ossification.
  • 15. FORMATION OF SECONDARY OSSIFICATION CENTER
  • 16. FORMATION OF SECONDARY OSSIFICATION CENTER  The epiphyseal plate continues to form new cartilage, which is replaced by bone, a process that increases the length of the bone.  Long bones have one or two secondary ossification centers.  Short bones have one ossification center.  The union of primary and secondary ossification center is called epiphyseal line.
  • 17.