TY - JOUR
T1 - Parathyroid hormone regulates transforming growth factor β1 and β2 synthesis in osteoblasts via divergent signaling pathways
AU - Wu, Yanhong
AU - Kumar, Rajiv
N1 - Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2000
Y1 - 2000
N2 - 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.
AB - 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.
KW - Osteoblast
KW - Parathyroid hormone
KW - Protein kinase A
KW - Protein kinase C
KW - Transforming growth factor β
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U2 - 10.1359/jbmr.2000.15.5.879
DO - 10.1359/jbmr.2000.15.5.879
M3 - Article
C2 - 10804017
AN - SCOPUS:0034099840
VL - 15
SP - 879
EP - 884
JO - Journal of Bone and Mineral Research
JF - Journal of Bone and Mineral Research
SN - 0884-0431
IS - 5
ER -