locomotor Flashcards
bone
A mineralized collagen-rich matrix which is very rigid and strong while still retaining some degree of flexibility
bone functions
• Resistance to compression : inorganic content • Resistance to tension : organic matrix
- Houses bone marrow
- Calcium homeostasis
- Protects vital organs
bone cells
– Osteoblasts bone forming – Osteocytes a mature osteoblast surrounded by bone matrix – Bone lining cells – Osteoclasts resorption and degradation of existing bone -osteoprognitor cells osteoblast precursors
bone structure and function
• Bone matrix / mineralisation • Bone remodelling • Bone development – Intramembranous – Endochondral
long bone anatomy
epiphysis metaphysis diaphysis metaphysis epiphysis
epiphyseal growth plate
- Specialised zone of cartilage
- Lies between epiphysis and metaphysis
- Site of longitudinal growth
- ‘Closes’ at /after puberty
- Long bone growth stops
bone - composition
• Cortical (70%) – compact • Trabecular (30%) – cancellous – medullary – spongy bone
bone - macroscopic organisation
• Proportion of cortical / cancellous bone varies in different parts and types of the bone • Mid bone / diaphysis – most cortical little cancellous bone • End of bone / epiphysis – predominantly cancellous bone
compact/ cortical bone
• Provides most structural support • Resists bending and torsion stresses – Thicker in mid part of bone
microscopic structure of cortical bone
• Osteons / Haversian canals – Main structural unit of cortical bone – Bone cylinders 2-3mm long – 8-15 concentric lamellae 0.2mm wide – Axis parallel to long axis of bone – Central cavity with blood vessels and nerve • Volkmann’s canals – Carry blood vessels from periosteum to Haversian system
microscopic structure of cancellous/ trabecular/ spongy bone
• Found inside cortices • Forms interconnecting network of plates / trabeculae • Provides large surface area for metabolic functions
Cancellous / Trabecular Bone
• Provides strength without disadvantage of weight • Organisation of trabecular plates is purposeful • Arranged along lines of maximum mechanical stress – Allows transmission of loads – Support areas of maximum stress • More metabolically active than cortical bone – Larger surface area
osteoid
• Unmineralised bone matrix – produced by osteoblasts • Type I collagen ( 90%) • Non collagenous proteins – Osteocalcin • Marker of bone formation – Osteonectin – Osteopontin – Growth factors
bone matrix - microscopic organisation
• Lamellar bone – Type I collagen fibres laid down in parallel sheets / lamellae – structurally very strong • Woven bone – collagen fibres randomly arranged – Mechanically weak – Formed when bone is being produced rapidly e.g. foetus or fracture
whats needed to from osteoblast
transcription factors Runx2 and osterix
osteoblast function
• Produce and deposit osteoid
• Regulate osteoclast differentiation / function – RANKL – RANK interactions [RANK(L)] = Receptor Activator of Nuclear Factor κ B [(ligand)]
osteoblast fate
• Life span 6 months – Osteoid production – 10 –15% entombed in bone – differentiate into osteocytes – Others die by apoptosis or differentiate into lining cells on quiescent bone
osteocytes
• Most common cell in bone • Reside in lacunae in cortical and trabecular bone – Connect to other osteocytes, osteoblasts and osteoclasts via long cytoplasmic processes
osteocyte function
Regulation of bone remodelling
• in response to local (biomechanical) or systemic
e.g. parathyroid hormone (PTH) signals
• increases osteoclast formation by increased
expression of RANKL = bone resorption
• inhibits osteoblast formation by production of
Sclerostin = decreased bone formation
• Sclerostin production inhibited by PTH and
mechanical loading = increased bone
formation
Calcium homeostasis
• Responds to increasing PTH levels by inducing
rapid calcium release (osteocytic osteolysis)
RANK-RANKL interaction
– induce precursor cell fusion and increase osteoclast
activity
– Regulated by Osteoprotegerin (OPG) a decoy receptor
that binds RANKL and inhibits osteoclast formation
preventing excessive bone resorption
– OPG secreted by osteoblasts and stromal cells
osteoclasts - 1
Monocyte / macrophage derived
multinucleate giant cells
Formation regulated by growth factors and
interactions between RANK (expressed by
osteoclast lineage) and RANKL expressed by
stromal cells / osteoblasts /osteocytes
osteoclasts 2
• Bind to mineralised bone surface • integrins • Resorb bone by production of – Acid to release calcium – Proteases to breakdown organic matrix • By-products of bone breakdown and osteoclast enzymatic activity are used as markers of bone resorption – Detected in blood or urine – Type I collagen fragments – N- and C-terminal cross-linked telopeptides – Tartrate-resistant acid phosphatase – Expressed by osteoclasts
mechanisms of bone formation and skeletal development
• Intramembranous ossification – Osteoid laid down by osteoblasts within loose fibroconnective tissue of a fibrous membrane • Endochondral ossification – Osteoid deposited on cartilage scaffolds
intramembranous ossification
• Formation of skull, maxilla
parts of clavicle/mandible
• Subperiosteal bone growth
• Fracture repair
endochondrial ossification
• Osteoid deposited on preformed cartilage – Development of most of the skeleton – Growth plates – Fracture repair • Programmed changes in chondrocyte – Hypertrophy, matrix vesicles, type X collagen secretion, chondrocyte death
primary centre of ossification
Genetically predetermined sites and times of ossification in diaphyses of
cartilage bones in utero
secondary centre of ossification
Ossification in epiphysis at or after birth Similar process to that of primary centre formation Line of cartilage between primary and secondary centres = epiphyseal (growth) plate
growth plate abnormalities - short
- Achondroplasia
- Achondrogenesis type II
- Multiple epiphyseal dysplasias
growth plate abnormalities - tall
Achondroplasia – mutation in fibroblast growth factor receptor 3 (FGFR3) – Receptor constitutively active – decreased chondrocyte proliferation and hypertrophy • Gigantism – excess growth hormone production before puberty – Increased longitudinal bone growth
