Department of Anatomy andDevelopmental Biology

University College London

BoneDevelopment

Tim Arnett

Bone development

Outline

• Bone composition – matrix + mineral• Bone formation - intramembranous & endochondral• Types of bone - woven & lamellar

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

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 / 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

Development of flat bones in human head(‘intramenbranous ossification’)

Intramenbranous ossificationBone formation without a cartilage model

Intramembranous ossificationBone formation without a cartilage model

Intramembranous ossificationNewly 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

trabecular, cancellous

cortical, compact

Limb bud development

chick 4.5 days chick 4.5 dayshuman 32 days

Cartilage

Simplest tissue

- no nerves, no blood vessels

- only cells + ECM

- primitive…

Cartilage composition

CELLSchondrocytes

FIBROUS COMPONENTcollagen type II(+ elastin)(+ collagen type I)

‘GROUND SUBSTANCE’glycosaminoglycansproteoglycans(→ aggregates)

EXTRACELLULARMATRIX

CARTILAGE

Cartilage types

Permanent cartilageeg articular cartilage

ear cartilage

trachea

Temporary cartilageeg 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 ossificationformation of long bones from cartilage model

Alberts et al Molecular – Molecular Biology of the Cell

Bone is highly vascular

Cartilage in developing footfirst stages of endochondral ossification

Cartilage in developing footfirst 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 developmentendochondral ossification

Endochondral ossificationformation of long bones from cartilage model

Alberts et al Molecular – Molecular Biology of the Cell

Adult human phalanx

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Key 1 = articular cartilage2 = cortical bone3 = trabecular bone4 = marrow5 = tendon

Adult human phalanx