PMID- 17241109
OWN - NLM
STAT- MEDLINE
DCOM- 20070627
LR  - 20091119
IS  - 1470-8736 (Electronic)
IS  - 0143-5221 (Linking)
VI  - 112
IP  - 11
DP  - 2007 Jun
TI  - Regulation and enzymatic basis of bone resorption by human osteoclasts.
PG  - 567-75
AB  - Although much has been learned recently of the mechanisms that regulate 
      osteoclastic differentiation, much less is known of the means through which their 
      resorptive activity is controlled. This is especially so for human osteoclasts. 
      We have recently developed an assay that allows us to measure resorptive activity 
      while minimizing confounding effects on differentiation by optimizing 
      osteoclastogenesis, so that measurable resorption occurs over a short period, and 
      by relating resorption in each culture during the test period to the resorption 
      that had occurred in the same culture in a prior control period. In the present 
      study, we found that RANKL (receptor activator of nuclear factor kappaB ligand) 
      strongly stimulated the release of CTX-I (C-terminal telopeptide degradation 
      product of type I collagen) by osteoclasts over a similar range to that over 
      which it induces osteoclastic differentiation, consistent with a distinct action 
      on osteoclastic function. CT (calcitonin) dose-dependently inhibited bone 
      resorption, whereas PTH (parathyroid hormone), IL (interleukin)-1, TNF-alpha 
      (tumour necrosis factor-alpha), IL-6, IL-8, VEGF (vascular endothelial growth 
      factor), MCP-1 (monocyte chemoattractant protein-1), MIP-1gamma (macrophage 
      inflammatory protein-1gamma), IFN (interferon)-gamma and dibutyryl cGMP had no 
      significant effect. Ca(2+), cyclosporin A, IFN-beta and dibutyryl cAMP all 
      strongly suppressed resorption. Bone resorption was also strongly suppressed by 
      alendronate, the cysteine protease inhibitor E64 and the cathepsin K inhibitor 
      MV061194. Inhibitors of MMPs (matrix metalloproteinases) had no effect on CTX-I 
      release. Moreover, the release of the MMP-derived collagen fragment ICTP 
      (C-terminal cross-linked telopeptide of type I collagen) represented less that 
      0.01% of the quantity of CTX-I released in our cultures. This suggests that MMPs 
      make, at most, a very small contribution to the bone-resorptive activity of 
      osteoclasts.
FAU - Fuller, Karen
AU  - Fuller K
AD  - Department of Cellular Pathology, St George's, University of London, Cranmer 
      Terrace, Tooting, London, UK.
FAU - Kirstein, Barrie
AU  - Kirstein B
FAU - Chambers, Timothy J
AU  - Chambers TJ
LA  - eng
GR  - Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Clin Sci (Lond)
JT  - Clinical science (London, England : 1979)
JID - 7905731
RN  - 0 (Bone Density Conservation Agents)
RN  - 0 (Collagen Type I)
RN  - 0 (Cytokines)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Peptides)
RN  - 0 (RANK Ligand)
RN  - 0 (TNFSF11 protein, human)
RN  - 0 (collagen type I trimeric cross-linked peptide)
RN  - 9007-12-9 (Calcitonin)
RN  - EC 3.4.- (Cathepsins)
RN  - EC 3.4.22.38 (CTSK protein, human)
RN  - EC 3.4.22.38 (Cathepsin K)
RN  - EC 3.4.24.- (Matrix Metalloproteinases)
SB  - IM
MH  - Adult
MH  - Bone Density Conservation Agents/pharmacology
MH  - Bone Resorption/*enzymology
MH  - Calcitonin/pharmacology
MH  - Cathepsin K
MH  - Cathepsins/*physiology
MH  - Cells, Cultured
MH  - Collagen Type I/metabolism
MH  - Cytokines/pharmacology
MH  - Enzyme Inhibitors/pharmacology
MH  - Female
MH  - Homeostasis/physiology
MH  - Humans
MH  - Male
MH  - Matrix Metalloproteinases/*physiology
MH  - Middle Aged
MH  - Osteoclasts/*enzymology
MH  - Peptides/metabolism
MH  - RANK Ligand/pharmacology
EDAT- 2007/01/24 09:00
MHDA- 2007/06/28 09:00
CRDT- 2007/01/24 09:00
PHST- 2007/01/24 09:00 [pubmed]
PHST- 2007/06/28 09:00 [medline]
PHST- 2007/01/24 09:00 [entrez]
AID - CS20060274 [pii]
AID - 10.1042/CS20060274 [doi]
PST - ppublish
SO  - Clin Sci (Lond). 2007 Jun;112(11):567-75. doi: 10.1042/CS20060274.