Acidosis environment promotes osteoclast formation by acting on the last phase of preosteoclast differentiation: a study to elucidate the action points of acidosis and search for putative target molecules

摘要: Acidosis promoted tartaric acid-resistant acid phosphatase-positive multinuclear cell (TRAP+MNC) or osteoclast formation. Large TRAP+LMNC formation was observed far more in an acidosis environment than a physiologically neutral environment. One of the major action points determined to be located last phase preosteoclast differentiation using co-culture system and soluble RANKL-dependent bone marrow culture system. On-going markedly deteriorated when medium replaced with within first 6h; however, cells previously stimulated for 9h differentiated into pH 7.4 medium. Messenger RNA (mRNA) expression levels DC-STAMP, key molecule fusion, NFATc1 did not increase compared those under conditions. Ruthenium red, general TRP antagonist, acidosis-promoted 4-Alpha-PDD, TRPV4-specific agonist, added 21 h differentiation, potentiated mild environment, showing synergism between TRPV4 activation acidosis. RN1734, partly inhibited We thus narrowed down elucidated characteristics this detail. Our results show that effectively uses drive large-scale fusion also utilizes systems independently TRPV4.