XXXX is a major stimulator of osteoclast formation and bone resorption.

@entity1568 @entity19 @entity1421 @entity26 @entity9332 @entity604 @entity520 @entity519 @entity79 @entity460 @entity35
@entity519 is known to act as a general stimulator of cells derived from marrow precursors. We investigated the effect of @entity26 tension on the formation and function of osteoclasts, the cells responsible for bore resorption, which are of promonocytic origin. Using 7- and 13-day cultures of @entity19 marrow cells on ivory discs, we found that reducing @entity26 tension from the ambient atmospheric level of 20% by increasing the proportion of @entity1568 caused progressive increases in the formation of multinucleated osteoclasts and resorption pits. Peak effects occurred in 2% @entity26 , where stimulations of resorption up to 21-fold were measured. Significant stimulations of osteoclast formation and resorption were observed even in severely @entity519 cultures gassed with 0.2% @entity26 . Short-term cultures of cells disaggregated from @entity35 bones indicated that @entity519 did not alter the resorptive activity of mature osteoclasts, but reduced their survival or adherence. In 3-day organ cultures of @entity19 calvarial bones, exposure to 2% @entity26 resulted in maximal, fivefold stimulation of osteoclast-mediated @entity460 release, an effect equivalent to that of @entity1421 ( @entity1421 ), a reference osteolytic agent. @entity519 also caused a moderate @entity520 in @entity9332 , presumably as a result of increased anaerobic metabolism; this observation is significant because osteoclast activation is dependent on extracellular acidification. Our experiments reveal a previously-overlooked mechanism of considerable potential importance for the regulation of @entity79 . These findings may help explain the @entity604 associated with a wide range of pathological states involving local or systemic @entity519 , and emphasize the importance of the vasculature in bone.
