Involvement of cholesterol in osteoclast-like cell formation via cellular fusion.
Osteoclasts, the bone resorbing cells, are formed from hematopoietic precursors via plasma membrane fusion. To investigate the possibility that cholesterol is involved in cellular fusion events, we examined the effects of the depletion of low density lipoproteins (LDL) and the effects of a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor on osteoclast-like cell formation. Tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells (MNCs), osteoclast-like cells, were formed as a result of the coculture of mouse spleen cells with mouse stromal cells TMS-14 in the presence of 1alpha, 25-dihydroxyvitamin D3 (1, 25 VD3). The depletion of LDL suppressed the formation of TRAP-positive MNCs, but the effect was abrogated by the addition of LDL. This inhibitory effect was not observed following the depletion of LDL in the early stages of the culture (day 0-3). The decrease in the number of TRAP-positive MNCs resulting from LDL depletion was accompanied by an increase in the number of TRAP-positive mononuclear cells. Furthermore, the formation of MNCs was also suppressed by the addition of simvastatin, an HMG-CoA reductase inhibitor. The inhibitory effect of simvastatin on the generation of TRAP-positive MNCs was dose and time dependent. However, treatment with simvastatin did not affect the increase in TRAP activities. These results suggest that cholesterol in the membranes of monocytes is involved in osteoclast-like cell formation via cellular membrane fusion events.
Department of Physiological Chemistry, Graduate School, Tokyo Medical and Dental University, Japan.
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Sato
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Morita
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Murota
D000135:Acid Phosphatase / Q000032:analysis; D000818:Animals; D002117:Calcitriol / Q000494:pharmacology; D002460:Cell Line; D002784:Cholesterol / Q000032:analysis*; D018920:Coculture Techniques / Q000379:methods; D015726:Giant Cells / Q000187:drug effects; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D000960:Hypolipidemic Agents / Q000494:pharmacology; D007527:Isoenzymes / Q000032:analysis; D008077:Lipoproteins, LDL / Q000032:analysis*; D008297:Male; D051379:Mice; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects*; D019821:Simvastatin / Q000494:pharmacology; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D017154:Stromal Cells / Q000187:drug effects; D000071681:Tartrate-Resistant Acid Phosphatase
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; D007527:Isoenzymes; D008077:Lipoproteins, LDL; D002784:Cholesterol; D019821:Simvastatin; D000135:Acid Phosphatase; C000605511:Acp5 protein, mouse; D000071681:Tartrate-Resistant Acid Phosphatase; D002117:Calcitriol