Bone Development Tim Arnett Department of Anatomy and Developmental Biology University College London
Bone development Outline Bone composition matrix + mineral Bone formation - intramembranous & endochondral Types of bone - woven & lamellar
Bone formation: cell lineages Neural crest flat bones of skull & jaw intramembranous ossification Paraxial mesoderm (somites) axial skeleton - vertebral column endochondral ossification Lateral plate mesoderm appendicular skeleton limbs endochondral ossification
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
Regulation of chondrogenic / osteogenic differentiation Osteogenic differentiation of mesenchymal cells induced when Wnt proteins (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
Development of flat bones in human head ( intramenbranous ossification )
Intramenbranous ossification Bone formation without a cartilage model
Intramembranous ossification Bone formation without a cartilage model
Intramembranous ossification Newly formed bone may be remodelled quickly by osteoclasts
Tooth eruption (cat) ultra-low power section of developing jaw 1 mm
Tooth eruption (cat) remodelling of alveolar bone to accommodate developing tooth
Tooth eruption (cat) remodelling of woven alveolar bone to accommodate tooth
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
Adult lamellar bone cortical, compact trabecular, cancellous
Limb bud development human 32 days chick 4.5 days chick 4.5 days
Cartilage Simplest tissue - no nerves, no blood vessels - only cells + ECM -primitive
Cartilage composition CELLS chondrocytes CARTILAGE FIBROUS COMPONENT collagen type II (+ elastin) (+ collagen type I) EXTRACELLULAR MATRIX GROUND SUBSTANCE glycosaminoglycans proteoglycans ( aggregates)
Cartilage types Permanent cartilage eg articular cartilage ear cartilage trachea Temporary cartilage eg epiphyseal growth plate Meckel s cartilage base of skull
Proliferation of chondrocytes interstitial cartilage growth Alberts et al Molecular Biology of the Cell
Hyaline cartilage - trachea
Hyaline cartilage - trachea
Adult knee joint articular cartilage
Endochondral ossification formation of long bones from cartilage model Alberts et al Molecular Molecular Biology of the Cell
Bone is highly vascular
Cartilage in developing foot first stages of endochondral ossification
Cartilage in developing foot first stages of endochondral ossification
Growing knee joint (cat) growth plates
Growing knee joint (cat) growth plate
Growing knee joint (cat) growth plate
Growing knee joint (cat) growth plate - bone formation on cartilage spicules
Vertebral development endochondral ossification
Endochondral ossification formation of long bones from cartilage model Alberts et al Molecular Molecular Biology of the Cell
Adult human phalanx 5 2 1 4 2 3 1 3 Key 1 = articular cartilage 2 = cortical bone 3 = trabecular bone 4 = marrow 5 = tendon
Adult human phalanx