Bone Growth and Development Flashcards
What is osteogenesis?
Process of bone formation
What are the two types of bone formation?
1) Endochondral Ossification
2) Intramembranous Ossification
What is endochondral ossification?
It is the bone formation from a cartilage template
What does endochondral ossification contribute to?
Contributes to increase bone length
What does endochondral ossification form?
All tubular and flat bones, vertebrae
Does endochondral ossification stop at a certain point?
Yes, it stops after skeletal maturity
What is intramembranous ossification?
It is the bone formation as a replacement of connective tissue, but in the absence of cartilage.
What does intramembranous ossification contribute to?
Contributes to increases in bone thickness
What does intramembranous ossification form?
Cortex of tubular and flat bones, facial bones, and most of cranial bones (skull)
Where does intramembranous ossification stop?
It doesn’t stop at any certain point - it remodels throughout life.
During development of the fetus, most bones of the skeleton have a ___________, which is gradually replaced by _________.
Cartilage template, bone
Describe the FIRST step in the fetal development of bone.
Loose connective tissue from the mesoderm called the mesenchyme condenses during embryogenesis.
Describe the SECOND step in the fetal development of bone.
Committed mesenchyme cells differentiate into chondrocytes that proliferate rapidly to form the model for bone.
- These chondrocytes produce a cartilage specific ECM
- The remaining mesenchymal cells surrounding the cartilage core form the perichondrium (outer membrane).
Describe the THIRD step in the fetal development of bone.
Centrally located chondrocytes stop dividing and undergo hypertrophy.
- Chondrocytes change to producing proteins that contribute to the mineralization of the matrix.
Describe the FOURTH step in the fetal development of bone.
Hypertrophic chondrocytes die by apoptosis (they die to leave space).
- This allows blood vessels to enter.
- There will be an invasion of osteoblasts and they will deposit bone matrix on partially degraded collagen.
Describe the FIFTH step in the fetal development of bone.
Perichondrium is converted to periosteum. Osteoblasts form a layer of bone around the diaphysis.
Describe the SIXTH step in the fetal development of bone.
Primary ossification center is established in the central portion of the diaphysis.
- Osteoblasts replace cartilage with spongy bone.
- Bone is formed until the diaphysis is filled.
- As bone grows, osteoclasts hollow out a marrow cavity
Describe the SEVENTH step in the fetal development of bone.
Bone formation and growth consists of ordered arrays of proliferating, hypertrophic, and mineralizing chondrocytes.
Describe the EIGHTH step in the fetal development of bone.
Secondary ossification centers form as blood vessels enter near the tips of bone.
Secondary centers of ossification:
1) Chondrocytes in the _____________ have been maturing and are invaded by _______________.
2) _____________ produce spongy bone that replaces ___________ cartilage.
3) Leaves ________ cartilage, and cartilage at ________________.
1) bone epiphyses, blood vessels
2) Osteoblasts, epiphyseal
3) articular, growth plate
What are the two basic processes of lengthening of long bones?
1) Growth of cartilage on the epiphyseal side of the growth plate.
2) Ossification of cartilage on the diaphyseal side of the growth plate.
What are the five zones of the epiphyseal growth plate?
1) Resting Zone
2) Proliferating Zone
3) Pre-Hypertrophic Zone
4) Hypertrophic Zone
5) Trabecular Zone
Describe the Resting Zone of the growth plate.
- Chondrocytes are closest to the epiphysis
- It is the source of chondrocytes that form the proliferation zone.
Describe the Proliferating Zone of the growth plate.
- Chondrocytes proliferate and flatten
- Chondrocytes are also laying down a cartilage matrix that will later serve as a scaffold for bone formation.
- This process pushes the epiphysis away from the diaphysis.
Describe the Pre-Hypertrophic Zone of the growth plate.
- Chondrocytes enter the maturation zone and begin to differentiate and enlarge.
- Cells produce additional molecules for the extracellular matrix including collagen fibers.
- This process builds cartilage.
Describe the Hypertrophic Zone of the growth plate.
- Chondrocytes and their lacunae become 5-12 times bigger.
- Chondrocytes eventually die, leaving behind a calcified cartilage matrix that is invaded by capillaries and osteoblasts.
Describe the Ossification Zone (Trabecular Bone) of the growth plate.
- Characterized by development of new bone
- Osteoblasts move into calcified cartilage matrix and deposit organic matrix.
- Osteoid + osteoblasts differentiation = ossification - Connection of adjacent osteocytes by cytoplasmic threads
- This leads to the development of spongy bone near the ends of the diaphysis.
The termination of long bone growth occurs as long as….
… the rate of cartilage growth is greater than the rate of bone formation within the growth plate.
Growth is finished when…
… the cartilage of the epiphyseal plate is eliminated.
When the cartilage of the epiphyseal plate is eliminated, what does that determine?
It determines an animal’s ultimate size. This is influenced by hormones, nutrition, minerals, and chronological age.
Spider lamb syndrome is also known as?
Chondrodysplasia
What kind of growth factor is involved in spider lamb syndrome?
Fibroblast Growth Factor 3 (FGF3) - it’s involved in the arrest of bone growth.
What does FGF3 restrict in spider lamb syndrome?
Restricts the proliferation (rapid increase) of pre-bone cartilage at the growth plate.
The receptor for FGF3 is highly expressed in resting and proliferative chondrocytes, but not in?
Not in hypertrophic chondrocytes
What does the SNP in the FGF3 Receptor gene result in?
Results in AA (amino acid) substitution in a tyrosine kinase domain of the receptor.
What does the SNP in the FGF3 Receptor gene enhance?
Enhances proliferation of pre-hypertrophic chondrocytes.
In a normal lamb, how does the FGF3 receptor work?
The receptor is activated and stops the proliferation of resting and proliferating chondrocytes, which LIMITS bone growth.
In a lamb with spider lamb syndrome, how does the FGF3 receptor work?
The receptor diminishes kinase activity, which promotes the proliferation of resting and proliferating chondrocytes, which leads to TOO MUCH bone growth
What does appositional bone growth do?
Increases the diameter of bone growth
Where does appositional bone growth occur?
Occurs by intramembranous ossification
Appositional bone growth is the process of how ___________ is formed.
Compact bone
What zone of the growth plate does the FGF3 receptor in spider lamb syndrome occur?
The resting zone and the proliferating zone.
Is the fetal development of bone an endochondral ossification process or an intramembranous ossification process?
Endochondral!
Is this Apoptosis or Necrosis?
- Programmed cell death
- Non-flammatory
Apoptosis
Is this Apoptosis or Necrosis?
- Response to a toxic environment or trauma
- Inflammatory
Necrosis
