Effects of osteoclast activating factor from human lymphocytes on cyclic AMP concentrations in isolated mouse bone and bone cells

Abstract

Osteoclast activating factor (OAF) is a lymphokine which may participate in the pathologic destruction of bone observed in a number of disorders. In the current studies, we investigated the action of OAF on cAMP accumulation by bones and isolated bone cells in culture. OAF was shown to stimulate accumulation of cAMP in mouse cranial bones at doses between 1 and 1000 ng/ml. Stimulation of bone resorption was observed in bones treated with the same doses of OAF. In order to investigate the cell types responsible for cAMP responses to OAF, we isolated bone cells and grew them in monolayer culture. The cells were isolated by a variety of techniques which separate bone cells into two types of parathyroid hormone (PTH)-responsive populations: (a) cells derived from the periosteal regions of the bone, which also respond to calcitonin with increases in cAMP; and (b) cells derived from the matrix, which do not respond to calcitonin. OAF caused elevation of cAMP levels in both the periosteum-derived cells and the matrix-derived cells. The magnitudes and time courses of OAF effects in these populations resembled the effects previously reported for PTH in the same populations. OAF stimulated adenyl cyclase in both types of cell populations, but did not produce significant changes in cAMP phosphodiesterase activity. OAF differed from PTH in that its effects on cAMP accumulation decreased sharply at supramaximal doses in both bone and isolated cells, especially in the matrix-derived populations. Bone resorption did not decrease as markedly as did cAMP accumulation at high doses of OAF, suggesting that cAMP accumulation and resorption could be dissociated under some conditions. These results indicate that OAF has effects on cAMP production in the same cell populations as PTH, and suggest that OAF could modify not only resorption but also formation of bone in vivo. OAF may exert its effects on bone by means of cAMP-dependent mechanisms, but more data will be necessary to establish this unequivocally. The observed differences between OAF and PTH may be of relevance in the mechanism and treatment of pathologic bone destruction in vivo.