Bone Biology & Limb Over Time

Bone Biology & Limb Over Time

1. SHAPE TYPES

   • Long
     • endochondral oss
   • Short
     • endochondral oss
   • Flat
     • intermembranous oss
   • Irregular
     • endochondral oss
     • intermembranous oss

2. CELLS

   • Osteoprogenitor Cells - undiff stem cells
     • Osteoblasts - lay down osteoid > bone
       • MATRIX
         • 50% Inorganic/mineral: Hydroxyapatite & Calcium Phosphate COMPRESSION STRENGTH
           • Lack > Rickets (children) / Osteomalacia (adults)
         • 25% Organic: Type I Collagen & Proteoglycans & Osteocalcin & GFs/cytokines/sialoproteins FLEXIBLE STRENGTH
           • Lack > Brittle bone disease (mut in gene for Type I collagen) Osteopetrosis (mut that affects osteoclast resorption)
             • HIGH BONE DENSITY - fractures - low blood cells prod - lose cranial nerve function
         • 25% H2O
       • Osteocytes - mature osteoblasts - trapped in bone lacunae - maintain bone matrix & mechanosensory role
       • (& ALP enzyme > calcification)
   • Osteoclasts - resorb bone. High SA - secrete protons to acidify ECF > matrix breakdown
   • Bone-lining cells - regulate mvmt of Ca2+ PO4-

3. TYPES

   • Cortical/Compact
     • • Osteon/Haversian system: lamellae, blood vessels, canaliculi, lacunae (cavities)
         • Lamellae: circumferential, concentric, interstitial
         • SLOW turnover
         • Type I collagen rich
   • Cancellous/Trabecular
     • • Contains bone marrow. Yellow BM = fat storage. vYellow BM ^Red BM as older
         • HIGH turnover
         • Wolff's Law remodelling
         • Haematopoesis

4. OSSIFICATION

   • Width: APPOSITIONAL. OB in periosteum secrete matrix > trapped as osteocytes. OC <>medullary cavity. Until skeletal maturity.
   • Length: ENDOCHONDRAL. Interstitial growth from cartilage at EPIPHYSEAL GROWTH PLATE. Until growth plates ossify.
   • Intermembranous (skull/vertebrae) > dermal bones > complete by 2yo
   • Endochondral (skeletal bones) > complete by teens/20s
   • BONE REMODELLING
     • Newly laid down bone = WOVEN (random collagen). Becomes LAMELLAR bone (ordered).
     • Causes
       • Mechanical - Wolf's Law - ^stress ^osteoblast activity and v-v
       • Genes - determine POTENTIAL shape/size but multifactorial. Influence growth hormone release; hormone receptors; gut's ability to absorb nut's
         • Dwarfism: anchondroplastic - short limb dwarfism
           • Affects gene coding for fibroblast GF 3. Affects chondroblast proliferating correctly - growth plate disfunction
       • Hormones - growth, sex, thryroid hormone > cell differentiation/metabolism
         • eg. overactive pituitary gland &gt; excess growth hormone
       • Disease eg. Osteoporosis - vOestrogen after menopause/Oophorectomy, extreme exercise, anorexia, smoking TRABECULAR BONE MOST AFFECTED
       • Aging - OB matrix production slows vs OC resorption. vCollagen deposition > more brittle, less flexible bone. Bone mass peaks 25/30yo.
     • Clinical relevance
       • OC > OB = Diuse Osteopenia > Osteoporosis (fractures)
       • OB > OC = Osteopetrosis (rock-like appearance)

5. CARTILAGE

   • STRUCTURE
     • Perichondrium
       • outer layer: dense, irregular CT w. fibroblasts. inner layer: fewer fibres w. chondroblasts
     • Superficial layer - look like fibroblasts. Middle layer - columns. Deep layer - round, larger, chondroblasts *see long bone ossification
   • TYPES
     • Fibrocartilage eg. meniscus
     • Hyaline eg. end of long bones/growth plate
       • Articular cartilage
         • GROWTH is similar to growth plate. Cell columns > calcified cartilage > bone. Arcades of Type II collagen fibrils anchor proteoglycan matrix to bone
           • Stops at similar time to growth plate but NEVER OSSIFIES
         • Properties
           • NO perichondrium (covers cartilage apart from ends of long bones)
           • Hypocellular, Aneural, Avascular
           • Smooth: reduces friction (heat>protein damage), low-wear surface
           • Deformable/elastic: ^SA vForce. Creep also ^SA during loading
     • Elastic eg. outer ear
   • CARTILAGE METABOLISM
     • Affectors
       • INJURY // REPAIR
         • Lack capillaries so nutrients from diffusion (from synovium). Chondrocytes secrete matrix (don't divide in adult). Tears never fully heal.
       • LIMB OVER TIME
         • Sarcopaenia
           • 'Flesh Poverty'
             • CONSQ's: Slower/weaker muscles, loss of coord, ^falls risk, ^dependency reduced loading can lead to sarcopaenia
         • Osteopaenia / Osteoporosis
           • Bone loss, vBMD, micro-architecture deteriorates
             • Cortical bone vTensile strength of (2%/decade 20yo+) vToughness (7%/decade=brittle)
               • vertebrae, hip, wrist most at risk
               • Trabecular bone more affected due to loss of trabeculae. Thinner ^porosity
           • Risk factors
             • 50% women, 30% men
               • vOestrogen & progesterone (also affect muscle)
             • Dietary Ca2+, Vit D/sunlight, ETOH, smoking, vBMI
         • Fibrous tissues
           • Ageing of Cartilage
             • Disc degeneration
               • Less PGs & H2O loss = Destruction of disc ^intradisc pressure
                 • >Vertebral osteoporotic fracture > kyphosis
               • Annulus Fibrosis = Type I collagen & protein Nucleus Pulposis = H2O & PGs
             • vPG & aggregation of PGs. ^Collagen & X-link. ^NEG. ^Apoptosis. ^Stiffness.
               • Impaired joint lubrication > friction/heat > fibrillation > OSTEOARTHRITIS
               • vChondrocytes (stop dividing at skeletal maturity). vCartilage cell density.
           • Cell content changes
             • eg. Tendons cells - Ageing elongates fibroblasts>fibrocytes and vConnectivity
           • Collagen X-links ^tissue strength&stiffness of ligaments. X-links increase & mature (become non-reducible)
           • NEG uncontrolled by cells (prob in tissues with low turnover) > tissue yellow/stiffer
     • Adaptive Remodelling. High strain ^matrix deposition ^matrix stiffness. Low strain ^matrix resorption vMatrix stiffness
     • TGF-B & IGF-1 = Growth Factors IL-1 & TNF = Cytokines

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