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Bone and Joint

Bone cell lineage and osteoblasts

Haematopoietic and mesenchymal lineages, osteoprogenitor cells and osteoblast biology

18 questions 3 source pages

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18 questions
Q1From which lineage do osteoclasts arise?▸
  • The haematopoietic monocyte/granulocyte cell lineage
Q2What are osteoclasts and how are they activated?▸
  • Multinucleated giant cells responsible for bone resorption
  • RANKL from osteoblasts binds immature osteoclasts, stimulating differentiation into active mature osteoclasts
Q3Which enzymes do osteoclasts use to hydrolyse organic matrix?▸
  • TRAP (tartrate-resistant isoenzymes of acid phosphatase)
  • Cysteine proteinases e.g. cathepsins
  • These are acidic proteolytic lysosomal enzymes
Q4List the steps of osteoclast bone resorption.▸
  • Migrate and attach to bone
  • Polarisation: orientate the ruffled border to bone
  • HA dissolution and matrix degradation
  • Degraded bone resorbed to lacunae
  • Apoptosis
Q5What activates osteoclasts? (PR6)▸
  • Continuous PTH acting on the osteoblast increases RANKL expression
  • RANKL (NfkappaB activator ligand) from the osteoblast
  • IL-6
Q6What inhibits osteoclasts? (CEO)10▸
  • Calcitonin
  • IL-10
  • Osteoprotegerin
  • Estrogen (decreases RANKL)
Q7Name other multinucleated giant cells.▸
  • Normal: osteoclast, megakaryocyte
  • Inflammation: macrophages, Kupffer cells, Langerhans cells
  • Neoplasm: Hodgkin, epithelial tumour
Q8From which cells are osteoblasts derived?▸
  • Osteoprogenitor cells, a mesenchymal stem cell line
  • BMP stimulates mesenchymal cells to become osteoprogenitor cells
Q9What are the characteristics of osteoblasts?▸
  • Abundant organelles for synthesis: Golgi apparatus, ER, mitochondria
  • Increased ALP activity and expression
Q10What are the functions of osteoblasts?▸
  • Bone forming: lay down osteoid (type 1 collagen + GAGs + osteocalcin, osteonectin) and are responsible for its mineralisation
  • Activate osteoclasts via the RANKL system
Q11What controls osteoblast differentiation?▸
  • Runx2/CBFA1 is the key molecular switch in commitment of osteoprogenitors to the osteoblast lineage, with cofactor Osterix
  • Osterix plays the important role later, in preosteoblast differentiation into mature osteoblasts
Q12What activates osteoblasts? (PED)▸
  • Pulsatile PTH
  • Estrogen (inhibits adenyl cyclase, decreasing RANKL synthesis)
  • 1,25 vitamin D (increases osteoblast matrix production and RANKL)
Q13What inhibits osteoblasts? (PPS)▸
  • Glucocorticoid
  • PTH (continuous)
  • PGE2 (activates adenyl cyclase)
Q14What are the osteotropic factors? (PPD11)▸
  • Vit D, PGE2, IL 11, PTH
  • They induce osteoclast formation by upregulating RANKL
Q15Which embryogenesis proteins also regulate osteoblast differentiation?▸
  • HOXA10, DLX and WNT
  • Typical of embryogenesis but also function in the adult skeleton to support osteoblast differentiation
Q16What is the role of Wnt/beta-catenin signalling in bone?▸
  • Wnt binds frizzled receptors with LRP5/6 co-receptors, stabilising beta-catenin and activating gene transcription
  • Favours osteoblastic differentiation, osteoblast maturation and survival
  • Inhibits osteoclast generation by increasing osteoprotegerin (OPG)
  • Sclerostin (SOST gene, inhibited by RUNX2) antagonises LRP5/6
Q17What can osteoprogenitor cells mature into?▸
  • Osteoblast, chondroblast or fibroblast
  • Depending on strain and oxygen tension
Q18Which theory describes this differentiation?▸
  • Perren's strain theory
  • Maturation depends on strain and oxygen tension
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