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Updated: Aug 17 2021

Bone Cells

Images cells.jpg
  • Osteoblasts
    • Origin
      • derived from undifferentiated mesenchymal cells
      • mesenchymal cells then differentiate into osteoprogenitor cells
    • Structure
      • contain increased amounts of endoplasmic reticulum, Golgi apparatus, and mitochondria than other cells
      • allows for synthesis and secretion of bone matrix
    • Function
      • form bone by producing non-mineralized matrix
        • alkaline phosphatase
        • type I collagen
        • osteonectin
        • osteocalcin
          • stimulated by 1,25 dihydroxyvitamin D
      • regulate osteoclast function
    • Signaling
      • osteoblastic differentiation
        • BMP stimulates mesenchymal cells to become osteoprogenitor cells
        • core binding factor alpha-1 (cbf alpha -1: RUNX2)
        • stable beta-catenin plays a major role in inducing cells to form osteoblasts with resulting intramembranous bone formation
        • platelet derived growth factor (PDGF) induces osteoblast differentiation
        • insulin derived growth factor (IDGF) induces osteoblast differentiation
      • osteoblast bone production
        • PTH receptor
          • stimulates alkaline phosphatase and type I collagen production
        • 1,25 dihydroxyvitamin D receptor
          • stimulates matrix and alkaline phosphatase synthesis
          • production of bone specific proteins (osteocalcin)
        • estrogen inhibits bone resorption and stimulates bone production by inhibiting adenylyl cyclase
        • glucocorticoids inhibit collagen and bone matrix production
        • prostaglandins stimulate bone resorption by activating adenylyl cyclase
      • osteoclast signaling
        • interconnected signaling allows coupling of bone resorption and formation
        • osteoclast activation
          • PTH receptors on osteoblast bind to PTH which when leads to expression of RANKL
          • RANKL binds to RANK receptor on osteoclast and bone resorption
        • osteoclast inhibition
          • osteoblasts can secrete OPG (osteoprotegrin)
          • OPG binds to RANKL on the osteoblast, preventing RANK activation
            • inhibits osteoclast activity
      • regulation of hematopoietic cells and immune response
        • occurs through the Jagged1-Notch pathway
          • PTH induces Jagged1 on osteoblasts
          • Jagged1 stimulates Notch receptors on the membrane of hematopoietic stem cells which results in cell proliferation
    • Location
      • more metabolically active cells at the bone surface
      • less active cells in more central bone
        • activated by disruption of the more peripheral osteoblasts
  • Osteoclasts
    • Function
      • reabsorb bone
        • osteoblasts regulate osteoclast bone reabsorbtion (see above)
        • steps in resorption cycle
          • migration to resorption site
          • bone attachment
          • polarization (formation of membrane domains)
          • dissolution of hydroxyapatite
          • degradation of organic matrix
          • removal of degradation products from resorption lacuna
          • apoptosis of the osteoclasts or return to the non-resorbing stage.
    • Origin
      • originate from myeloid hematopoietic cells from monocyte/macrophage cell lineage
      • monocyte progenitors fuse together to form mature multinuclear cells
    • Cellular biology
      • cellular anatomy
        • multinucleated giant cells
      • cellular physiology
        • bone reabsorbtion occurs at ruffled border
          • Howship's lacunae
            • are site of bone resorption where ruffled border meets bone surface
          • tartrate-resistant acid phosphatase
            • secreted by osteoclasts to lowers the Ph (utilizing carbonic anhydrase) and increases the solubility of hydroxyapatite crystals
              • deficiency of carbonic anhydrase prevents bone resorption
          • proteolytic digestion
            • the organic matrix is then removed by proteolytic digestion
            • cathepsin K
              • is one major proteolytic enzyme that degests organic matrix at ruffled border
          • bisphosphonates mechanism
            • prevents osteoclasts from forming ruffled border and producing acid hydrolases
    • Molecular biology
      • osteoclast-bone attachment
        • osteoclast attaches to bone matrix at sealing zone
        • attach to bone surfaces via integrins on osteoclast surface
          • integrins include αVβ3, αVβ5, α2β1, αVβ1
            • αVβ3 (on osteoclast) is a receptor for vitronectin (on bone surface)
            • Arg-Gly-Asp (RGD) sequence of extracellular bone proteins directly allows binding to integrins
              • antibodies to αVβ3 and RGD inhibit bone resorption
      • osteoclast polarization
        • contain specialized membrane domains
          • ruffled border (RB)
          • functional secretory domain (FSD)
          • basolateral membrane (BL)
      • mineralized bone matrix degradation
        • hydroxyapatite crystals dissolved by HCl secreted through ruffled border into resorption lacuna (RL)
          • RL is an extracelllular space between RB and bone matrix, sealed from ECF by sealing zone
          • uses ATP-consuming proton pumps in RB and in intracellular vacuoles
            • H+ come from carbonic anhydrase II
          • RB has high number of chloride channels (maintain electroneutrality)
      • organic bone matrix degradation
        • lysosomal cysteine proteinases
        • matrix metaloproteinases (MMPs), esp MMP-9
        • cathepsin K
          • mutation in cathepsin K gene leads to pycnodysostosis
      • removal of degradation products
        • by transcystosis to FSD, where they are secreted into ECF
        • tartrate-resistant acid phosphatase (TRAP) is localized in transcytotic vesicles, generates reactive O2 species that destroys collagen
      • osteoclast-osteoblast signaling
        • osteoblasts upregulate and downregulate osteoclast activity
          • osteoclast activation
            • RANKL (NF-kB ligand)
              • expressed by osteoblasts and tumor cells to activate osteoclasts
            • IL-1
              • found adjacent to loose total joint implants and known to activate osteoclasts
          • osteoclast inhibition
            • calcitonin
            • IL-10
  • Osteocytes
    • Origin
      • are former osteoblasts trapped in the matrix they produced
      • account for 90% of cells in the mature skeleton
    • Structure
      • high nucleus to cytoplasm ratio
      • have long cellular processes which communicate with other cells via canalculi in the bone
    • Function
      • maintain bone and cellular matrix
      • important in regulation of calcium and phosphorous concentrations in bone
      • do not express alkaline phosphatase
    • Signaling
      • stimulated by calcitonin
      • inhibited by PTH
      • communicate with adjacent osteocytes via gap junctions in canaliculi
  • Osteoprogenitor Cells
    • Origin
      • originate from mesenchymal stem cells
      • environment will determine their function
    • Function
      • become osteoblasts under low strain and high oxygen tension
      • become cartilage under intermediate strain and low oxygen tension
      • become fibrous tissue under high strain
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