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A comparison of the PTH-dependent cAMP responses in osteoclastic and osteoblastic bone cells
Abstract:
Isolated bone cells enriched for either osteoclastic (OC) or osteoblastic (OB) characteristics have been previously described. Only OC cells respond to calcitonin (sCT), but both types of cell populations demonstrate adenosine 3':5'-cyclic phosphate (cAMP) increases with parathyroid hormone (PTH), suggesting a common PTH-responsive cell in both. In view of this, the cAMP responses to PTH were compared in terms of turnover time, induction of dose-dependent desensitization, recovery from desensitization and inhibition by trifluoperazine (TFP). In the absence of new protein synthesis, OC cell cAMP response to PTH declined more slowly than that of OB cells (t/2 of approximately 24 h vs. 8 h for OB cells). The relative stability of PTH responsiveness in OC cells was unique in that the same was not seen for sCT or prostaglandin E1 (PGE1) responsiveness which declined with a t/2 of 8 and 6 h, respectively. In comparison to OB cells, OC cells also demonstrated (1) a more rapid recovery from autologous desensitization with PTH, regaining responsiveness with a t/2 of approximately 6 h vs. 14 h for OB cells; (2) greater resistance to desensitization by submaximal doses of PTH (4 X 10(-10) -4 X 10(-9) M), and (3) resistance to inhibition by low doses of TFP (less than 5 microM). These results suggest that the PTH-responsive cells in OC populations are metabolically different from those in OB populations.