Publication: Recent advances in osteoclast biology and pathological bone resorption
Authors
Blair, H.C. ; Athanasou, N.A.
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Publisher
Murcia : F. Hernández
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DOI
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info:eu-repo/semantics/article
Description
Abstract
The osteoclast is a bone-degrading
polykaryon. Recent studies have clarified the
differentiation of this cell and the biochemical
mechanisms it uses to resorb bone. The osteoclast
derives from a monocyte/macrophage precursor.
Osteoclast formation requires permissive concentrations
of M-CSF and is driven by contact with mesenchymal
cells in bone that bear the TNF-family ligand RANKL.
Osteoclast precursors express RANK, and the interaction
between RANKL and RANK (which is inhibited by
OPG) is the major determinant of osteoclast formation.
Hormones, such as PTH/PTHrP, glucocorticoids and
1,25(OH)2D3, and humoral factors, including TNFa,
interleukin-1, TGFß and prostaglandins, influence
osteoclast formation by altering expression of these
molecular factors. TNFa, IL-6 and IL-11 have also been
shown to promote osteoclast formation by RANKLindependent
processes. RANKL-dependent/independent
osteoclast formation is likely to play an important role in
conditions where there is pathological bone resorption
such as inflammatory arthritis and malignant bone
resorption. Osteoclast functional defects cause sclerotic
bone disorders, many of which have recently been
identified as specific genetic defects. Osteoclasts express
specialized proteins including a vacuolar-type H+-
ATPase that drives HCl secretion for dissolution of bone
mineral. One v-ATPase component, the 116 kD V0
subunit, has several isoforms. Only one isoform TCIRG1, is up-regulated in osteoclasts. Defects in
TCIRG1 are common causes of osteopetrosis. HCl
secretion is dependent on chloride channels; a chloride
channel homologue, CLCN7, is another common defect
in osteopetrosis. Humans who are deficient in carbonic
anhydrase II or who have defects in phagocytosis also
have variable defects in bone remodelling. Organic bone
matrix is degraded by thiol proteinases, principally cathepsin K, and abnormalities in cathepsin K cause
another sclerotic bone disorder, pycnodysostosis. Thus,
bone turnover in normal subjects depends on relative
expression of key cytokines, and defects in osteoclastic
turnover usually reflect defects in specific ion
transporters or enzymes that play essential roles in bone
degradation.
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