The activation of cAMP-dependent protein kinase is directly linked to the inhibition of osteoblast proliferation (UMR-106) by parathyroid hormone-related protein

The present study was performed to compare the effect of parathyroid hormone-related protein(PTHrP) on the proliferation of osteoblastic osteosarcoma cells (UMR-106) with that of PTH and characterize the direct involvement of cAMP in the change of osteoblast proliferation by PTHrP. Human(h)PTHrP-(1–34) (10 −11 –10 −7 M) dose-dependently inhibited [ 3 H]thymidine incorporation (TdR) in the same manner as hPTH-(1–34). The simultaneous addition of PTHrP and PTH at a maximal effective dose of 10 −7 M did not cause additive suppressive effect on cell proliferation. Rp-cAMPS,which has been recently shown to act directly as antagonist in the activation of cAMP-dependent protein kinase (PKA), dose-dependently (10 −6 –10 −4 M) antagonized PTHrP-induced suppression of TdR in the same manner as PTH. Present study indicated that PTHrP has the same effect on osteoblast proliferation as PTH and that the activation of PKA is directly linked to the change of osteoblast proliferation by PTHrP.