TARTRATE-RESISTANT ACID-PHOSPHATASE-ACTIVITY IN RAT CULTURED OSTEOCLASTS IS INHIBITED BY A CARBOXYL-TERMINAL PEPTIDE (OSTEOSTATIN) FROM PARATHYROID HORMONE-RELATED PROTEIN

A carboxyl-terminal peptide sequence (''osteostatin'') from parathyroi d hormone related protein has been shown to have an inhibitory effect on osteoclastic bone resorption-an action opposite to its amino-termin al sequence. In this study, we proposed that inhibition of osteoclasti c bone resorption by osteostatin was associated with reduction of tart rate resistant acid phosphatase (TRAcP) activity in osteoclasts. Our r esults have indicated that osteostatin reduced TRAcP activity in a dos e dependent manner. This effect of osteostatin was both sensitive (hal f maximal effect approximately 5 x 10(-13) M) and potent (maximum inhi bition approximately 50% of control). In the first 90 min of treatment , however, reduction of TRAcP activity was erratic but became persiste nt and progressive when the time course was extended. Moreover, throug hout the experimental period the levels of TRAcP activity in the cultu re medium had fallen significantly. It appears that osteostatin has a biphasic effect on TRAcP activity, inhibiting its secretion and either suppressing its synthesis or increasing its degradation. In addition, osteostatin induced rapid cellular retraction of both human and rat c ultured osteoclasts, which was morphologically distinct from that prod uced by calcitonin. (C) 1994 Wiley-Liss, Inc.