bone - university college londonucgatma/anat3048/lectures... · bone formation: cell lineages...
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Department of Anatomy andDevelopmental Biology
University College London
BoneDevelopment
Tim Arnett
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Bone development
Outline
• Bone composition – matrix + mineral• Bone formation - intramembranous & endochondral• Types of bone - woven & lamellar
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Bone formation: cell lineages
Lateral plate mesodermappendicular skeleton – limbsendochondral ossification
Neural crestflat bones of skull & jawintramembranous ossification
Paraxial mesoderm (somites)axial skeleton - vertebral column endochondral ossification
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Two processes of bone formation(ossification)
Intramembranous ossification Flat bones - osteoblasts differentiate from progenitors and form bone directly
Endochondral ossification Long bones - formed initially as a cartilage model which is then replaced by bone
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Regulation of chondrogenic / osteogenicdifferentiation
Osteogenic differentiation of mesenchymal cells induced when Wntproteins (350-400 a.a. ‘cytokines’) bind to LRP 5/6 & Frizzled co-receptors
→ stabilisation / accumulation of β-catenin
→ increased expression of Runx2 (Cbfa1) - osteogenic transcription factor
→ increased expression of Osx (Osterix) - osteogenic transcription factor
+ decreased expression of genes required for chondrogenesis
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Development of flat bones in human head(‘intramenbranous ossification’)
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Intramenbranous ossificationBone formation without a cartilage model
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Intramembranous ossificationBone formation without a cartilage model
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Intramembranous ossificationNewly formed bone may be remodelled quickly by osteoclasts
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Tooth eruption (cat)ultra-low power section of developing jaw
1 mm
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Tooth eruption (cat)remodelling of alveolar bone to accommodate developing tooth
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Tooth eruption (cat)remodelling of woven alveolar bone to accommodate tooth
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Two types of bone
Woven (immature, fracture)
large, rounded osteocytes
osteocytes irregularly spaced
randomly oriented collagen fibres
variable collagen fibre diameter
rapid matrix mineralisation
forms rapidly
rapid turnover
Lamellar (mature, adult)
smaller, flattened osteocytes
osteocytes regularly spaced
collagen fibres show regular, “plywood” orientation – confers strength
regular collagen fibre diameter
delayed matrix mineralisation (few days)
forms slowly
slow turnover
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Adult lamellar bone
trabecular, cancellous
cortical, compact
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Limb bud development
chick 4.5 days chick 4.5 dayshuman 32 days
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Cartilage
Simplest tissue
- no nerves, no blood vessels
- only cells + ECM
- primitive…
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Cartilage composition
CELLSchondrocytes
FIBROUS COMPONENTcollagen type II(+ elastin)(+ collagen type I)
‘GROUND SUBSTANCE’glycosaminoglycansproteoglycans(→ aggregates)
EXTRACELLULARMATRIX
CARTILAGE
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Cartilage types
Permanent cartilageeg articular cartilage
ear cartilage
trachea
Temporary cartilageeg epiphyseal growth plate
Meckel’s cartilage
base of skull
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Proliferation of chondrocytes
interstitial cartilage growth
Alberts et al – Molecular Biology of the Cell
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Hyaline cartilage - trachea
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Hyaline cartilage - trachea
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Adult knee joint – articular cartilage
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Endochondral ossificationformation of long bones from cartilage model
Alberts et al Molecular – Molecular Biology of the Cell
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Bone is highly vascular
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Cartilage in developing footfirst stages of endochondral ossification
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Cartilage in developing footfirst stages of endochondral ossification
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Growing knee joint (cat)growth plates
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Growing knee joint (cat)growth plate
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Growing knee joint (cat)growth plate
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Growing knee joint (cat)growth plate - bone formation on cartilage spicules
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Vertebral developmentendochondral ossification
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Endochondral ossificationformation of long bones from cartilage model
Alberts et al Molecular – Molecular Biology of the Cell
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Adult human phalanx
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Key 1 = articular cartilage2 = cortical bone3 = trabecular bone4 = marrow5 = tendon
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Adult human phalanx