CELLULAR AND HORMONAL FACTORS INFLUENCING MONOCYTE DIFFERENTIATION TOOSTEOCLASTIC BONE-RESORBING CELLS

Osteoclasts are multinucleated cells which form by fusion of circulati ng mononuclear hemopoietic precursors. The nature of these precursor c ells and the roles bone stromal cells and hormonal factors play in the ir differentiation to osteoclasts are unknown. We cocultured adherent murine blood monocytes (nonspecific esterase and F4/80 positive; tartr ate-resistant acid phosphatase negative) with osteoblastic and fibrobl astic stromal cell lines in the presence of 2 x 10(-8) M 1,25-dihydrox yvitamin D-3 [1,25-(OH)(2)D-3]. Tartrate-resistant acid phosphatase an d calcitonin (CT) receptor-positive osteoclastic cells, which formed n umerous resorption pits in, vitro, were noted after only 4 days in coc ulture with UMR106 osteoblast-like cells. Resorption was seen in cocul tures to which as few as 100 peripheral blood mononuclear cells had be en added. 1,25-(OH)(2)D-3 and contact with live bone stromal cells wer e absolute requirements for monocyte differentiation into boneresorbin g cells. Both salmon CT (5 IU/ml) and prostaglandin E(2) (10(-6) M) si gnificantly inhibited bone resorption. Thus, a significant proportion of the peripheral blood mononuclear cells in the monocyte fraction are capable of differentiating into cells showing the cytochemical and fu nctional characteristics of osteoclasts. The presence of specific horm onal [1,25-(OH)(2)D-3] and bone stromal cell elements is necessary for this process to occur; the resultant resorption can be modulated by k nown inhibitors of bone resorption, CT and prostaglandin E(2).