Secretion of tartrate-resistant acid phosphatase by osteoclasts correlates with resorptive behavior

There have been dramatic advances recently in our understanding of the regulation of osteoclastic differentiation. However, much less is known of the mechanisms responsible for the induction and modulation of resorptive behavior. We have developed a strategy whereby osteoclasts can be generated in vitro and released into suspension in a fully-functional state. We now exploit this approach to show that tartrate-resistant acid phosphatase (TRAP) is released by osteoclasts during bone resorption. TRAP release was inhibited by the secretion-inhibitor Brefeldin A, and was not accompanied by LDH release. This suggests that TRAP release is due to secretion, rather than cell death. Consistent with this, TRAP secretion was stimulated by resorbogenic cytokines, was inhibited by the resorption-inhibitor calcitonin, and correlated with excavation of the bone surface. We found that, in contrast to incubation on bone, incubation on plastic, glass, or vitronectin-coated plastic substrates did not induce secretion of TRAP. This suggests that the induction of resorptive behavior in osteoclasts depends upon stimulation by bone matrix of a putative osteoclastic "mineral receptor." Release of TRAP by osteoclasts thus represents not only a productive approach to the analysis of the mechanisms that modulate the rate of resorptive activity, but also a system whereby the mechanism through which bone substrates induce resorptive behavior can be identified.