Bone. Development. Tim Arnett. University College London. Department of Anatomy and Developmental Biology

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1 Bone Development Tim Arnett Department of Anatomy and Developmental Biology University College London

2 Bone development Outline Bone composition matrix + mineral Bone formation - intramembranous & endochondral Types of bone - woven & lamellar

3 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

4 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

5 Regulation of chondrogenic / osteogenic differentiation Osteogenic differentiation of mesenchymal cells induced when Wnt proteins ( 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

6 Development of flat bones in human head ( intramenbranous ossification )

7 Intramenbranous ossification Bone formation without a cartilage model

8 Intramembranous ossification Bone formation without a cartilage model

9 Intramembranous ossification Newly formed bone may be remodelled quickly by osteoclasts

10 Tooth eruption (cat) ultra-low power section of developing jaw 1 mm

11 Tooth eruption (cat) remodelling of alveolar bone to accommodate developing tooth

12 Tooth eruption (cat) remodelling of woven alveolar bone to accommodate tooth

13 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

14 Adult lamellar bone cortical, compact trabecular, cancellous

15 Limb bud development human 32 days chick 4.5 days chick 4.5 days

16 Cartilage Simplest tissue - no nerves, no blood vessels - only cells + ECM -primitive

17 Cartilage composition CELLS chondrocytes CARTILAGE FIBROUS COMPONENT collagen type II (+ elastin) (+ collagen type I) EXTRACELLULAR MATRIX GROUND SUBSTANCE glycosaminoglycans proteoglycans ( aggregates)

18 Cartilage types Permanent cartilage eg articular cartilage ear cartilage trachea Temporary cartilage eg epiphyseal growth plate Meckel s cartilage base of skull

19 Proliferation of chondrocytes interstitial cartilage growth Alberts et al Molecular Biology of the Cell

20 Hyaline cartilage - trachea

21 Hyaline cartilage - trachea

22 Adult knee joint articular cartilage

23 Endochondral ossification formation of long bones from cartilage model Alberts et al Molecular Molecular Biology of the Cell

24 Bone is highly vascular

25 Cartilage in developing foot first stages of endochondral ossification

26 Cartilage in developing foot first stages of endochondral ossification

27 Growing knee joint (cat) growth plates

28 Growing knee joint (cat) growth plate

29 Growing knee joint (cat) growth plate

30 Growing knee joint (cat) growth plate - bone formation on cartilage spicules

31 Vertebral development endochondral ossification

32 Endochondral ossification formation of long bones from cartilage model Alberts et al Molecular Molecular Biology of the Cell

33 Adult human phalanx Key 1 = articular cartilage 2 = cortical bone 3 = trabecular bone 4 = marrow 5 = tendon

34 Adult human phalanx

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