Biochemistry Of Bone Remodelling And Osteoperosis Flashcards
(37 cards)
List the 4 main types of bone cells.
Osteogenic cells, osteoblasts, osteoclasts and osteocytes.
Describe osteoblasts and their function.
- mononucleated, basophilic and cuboidal in shape.
- Osteoblasts make bone.
- They synthesise uncalcified/unmineralised ECM called osteoid. This later becomes calcified/mineralised to form bone.
- become osteocytes when trapped in ECM
Describe osteocytes and their function.
- mononucleated, few organelles, ellipsoid cell body
- dendritic projections which can form gap junctions for communication
- maintain daily metabolism of bone including exchange of nutrients and waste with blood
- regulate function of osteoblasts and osteoclasts in response to mechanical and hormonal signalling
Describe osteoclasts and their function.
- edge of cell closest to bone has a ruffled border
- large and multinucleated
- powerful lysosomal enzymes and acids released to digest ECM
- removal/resorption of bone during normal development, maintenance and repair
Where are osteogenic cells usually found?
Alongside the membranes that surround the bones and the blood vessels in bone canals.
Where are osteoblasts derived from and where are they usually found?
- derived from osteogenic cells
- usually found in regions of bone formation (normal development or remodelling)
Where are osteocytes derived from and where are they usually found?
- when osteoblasts get trapped in ECM they become osteocytes
- found within matrix of bone
Where are osteoclasts derived from and where are they usually found?
- derived from fusion of monocytes present within bone marrow or other blood producing tissue
- lie in close contact with bone surface in resorption bays known as Howship’s lacunae
- mainly concentrated within layer of connective tissue found on inside of bone
What are Howship’s lacunae?
Resorption bays in close contact with the bone surface in which osteoclasts are usually found.
List some factors/molecules involved in osteoblast proliferation and differentiation.
- PTH (parathyroid hormone)
- glucocorticoids
- Wnt
- TGF-b
- hedgehog
- BMPs
- FGF
- IGF
What is sclerostin?
A negative regulatory protein produced only by mature osteocytes. It inhibits bone formation by osteoblasts and enhances apoptosis of osteoblasts.
What is osteoprotegerin?
A RANKL binding decoy cytokine that modulates RANK/RANKL interaction.
What is MCSF?
- Macrophage colony stimulating factor
- a survival factor for cells of monocyte/macrophage/osteoclast lineage
List some factors which regulate osteoclasts formation and activity.
- E2
- glucocorticoids
- PTH (parathyroid hormone)
- vitamin D3
- IL-1
- TNFa
- IFNy
What is RANKL?
- The receptor activator of NF-kB ligand
- member of TNF ligand family
- attaches to RANK to stimulate proliferation and differentiation of osteoclasts and inhibit their apoptosis
What is RANK?
- A receptor on the surface of osteoclasts and osteoclast precursors
- when RANKL binds to RANK, osteoclast proliferation and differentiation is stimulated and apoptosis inhibited
What is CBFA1?
- core binding factor alpha 1
- essential in osteoblast differentiation and bone formation
List some factors which can stimulate osteoblast expression of RANKL.
- TNF-a
- PTHrP (parathyroid hormone related peptide)
- IL-1
- IL-11
- Vitamin D
- glucocorticoids
- PTH
- PGE2 (prostaglandin E2)
Describe the bone remodelling cycle.
Quiescence > osteoclast recruitment, differentiation, activation > resorption > osteoclast apoptosis, removal > reversal > osteoblast recruitment, differentiation, activation > matrix synthesis > formation > mineralisation > quiescence
Does OPG stimulate or inhibit osteoclast formation?
Inhibits by binding to RANK so that RANKL cannot.
How are Wnt proteins involved in bone formation and resorption?
- act on osteoblast precursor cells and promote differentiation into mature osteoblasts
- suppress bone resorption by regulating RANKL/OPG ratio
How do osteoclasts bind to bone matrix?
Via integrins
What do osteoclasts secrete do resorb bone?
Acid and cathepsin K
When does primary mineralisation occur?
Within the first 100 days following remodelling.
