Parathyroid hormone regulates transforming growth factor β1 and β2 synthesis in osteoblasts via divergent signaling pathways

Yanhong Wu, Rajiv Kumar

Research output: Contribution to journalArticle

45 Scopus citations

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-β 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 Go6976 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(134)-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 PICA pathway.

Original languageEnglish (US)
Pages (from-to)879-884
Number of pages6
JournalJournal of Bone and Mineral Research
Volume15
Issue number5
DOIs
StatePublished - 2000

Keywords

  • Osteoblast
  • Parathyroid hormone
  • Protein kinase A
  • Protein kinase C
  • Transforming growth factor β

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine

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