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

Abstract

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, UMP-106. Sp-cAMPS (10 −6–10 −4M)inhibited TdR in a dose-dependent manner. Although Rp-cAMPS (10 −6–10 −4M) itself did not affect TdR, it significantly blocked dbcAMP-, cholera toxin- and Sp-cAMPS-induced suppression of TdR. Moreover, Rp-cAMPS (10 −6–10 −4M) 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.