Wu, Yanhong

Abstract Parathyroid hormone 1–34 [PTH(1–34)] was shown to increase transforming growth factor β1 (TGF-β1) and TGF-β2 concentrations in supernatants of cultured human osteoblasts and to increase TGF-β1 and TGF-β2 messenger RNA (mRNA) concentrations and gene transcription in these cells. Because PTH(1–34) activates both protein kinase C (PKC) and protein kinase A (PKA) pathways in osteoblasts, we investigated the role of each kinase pathway in activation of TGF-β3 isoforms. PTH(29–32), which activates the PKC pathway in rat osteoblasts, increased TGF-β1 but not TGF-β2 concentrations in supernatants of osteoblasts. Phorbol myristate acetate (PMA), a PKC agonist, increased TGF-β1 but not TGF-β2 concentrations. Specific PKC antagonists safingol and Gö6976 attenuated PTH(1–34)-mediated increases in TGF-β1 but not TGF-β2 synthesis. PTH(1–31), which increases PKA activity in several cell culture systems, increased TGF-β2 but not TGF-β1 concentrations in human osteoblast supernatants. Forskolin, a PKA agonist, increased TGF-β2 but not TGF-β1 concentrations in supernatants of human osteoblasts. The PKA antagonist H-89 blunted PTH(1–34)-mediated increases in TGF-β2 but not TGF-β1 synthesis. Our results are consistent with the concept that PTH increases TGF-β1 expression and secretion by pathways that involve the PKC pathway, whereas it increases TGF-β2 expression and secretion via the PKA pathway. (J Bone Miner Res 2000;15:879–884)