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

In order to characterize the direct involvement of cAMP in the change of osteoblast proliferation by parathyroid hormone (PTH), we employed the diastereoisomers of adenosine 3',5'-cyclic phosphorothioate, Sp-cAMPS and Rp-cAMPS, which have been recently shown to act directly as agonist and antagonist, respectively in the activation of cAMP-dependent protein kinase (PKA). Dibutyryl cAMP (dbcAMP) and cholera toxin as well as human(h) PTH-(1-34) significantly inhibited [3H]thymidine incorporation (TdR) in osteoblastic osteosarcoma cells, UMR-106. Sp-cAMPS (10(-6)-10(-4) M) inhibited TdR in a dose-dependent manner. Although Rp-cAMPS (10(-6)-10(-4) M) itself did not affect TdR, it significantly blocked dbcAMP-, cholera toxin- and Sp-cAMPS-induced suppression of TdR. Moreover, Rp-cAMPS (10(-6)-10(-4) M) dose-dependently antagonized hPTH-induced suppression of TdR. Present studies first indicated that the activation of PKA is directly linked to the change of osteoblast proliferation by PTH.