INVOLVEMENT OF DUAL SIGNAL-TRANSDUCTION SYSTEMS IN THE STIMULATION OF OSTEOCLAST-LIKE CELL-FORMATION BY PARATHYROID-HORMONE AND PARATHYROID HORMONE-RELATED PEPTIDE

The present study was performed to examine whether parathyroid hormone (PTH) and parathyroid hormone-related peptide (PTHrP) would stimulate osteoclast-like cell formation via soluble factor(s) released from osteoblast and, if so, to characterize the involvement of PTH/PTHrP-responsive dual signal transduction systems [cAMP-dependent protein kinase (PKA) and calcium/protein kinase C (PKC)]. Osteoblast-conditioned medium (CM) was obtained from rat osteoblastic osteosarcoma cells (UMR-106 cells), which had been cultured in serum free medium for 24 hrs after treatment with various kinds of reagents. The CM of osteoblasts treated with either 10−7 M human (h)PTH-(1-34) or 10−7 M hPTHrP-(1-34) equally stimulated osteoclast-like cell formation from hemopoietic blast cells derived from mouse spleen cells, although the CM treated with 10−8 M 1,25-dihydroxyvitamin-D3 failed to affect it. The CM treated with both 10−4 M dibutyryl-cAMP and a direct PKA activator, 10−4 M Sp-cAMPS significantly increased osteoclast-like cell formation. The CM treated with PKC activator, 10−7 M phorbol 12-myristate 13-acetate (PMA) and calcium ionophores (10−7 M A23187 and 10−7 M ionomycin) also significantly enhanced osteoclast-like cell formation. The present study first indicated the osteoblast-mediated stimulation of osteoclast-like cell formation by PTH and PTHrP, and the participation of PTH/PTHrP-responsive dual signal transduction systems of osteoblasts in the stimulation of osteoclast-like cell formation by PTH and PTHrP. © 1993 Academic Press, Inc.