The direct involvement of cAMP-dependent protein kinase in the regulation of collagen synthesis by parathyroid hormone (PTH) and PTH-related peptide in osteoblast-like osteosarcoma cells (UMR-106).
The present study was performed to characterize the direct involvement of cAMP-dependent protein kinase (PKA) in the regulation of collagen synthesis by parathyroid hormone (PTH) and PTH-related peptide (PTHrP) in osteoblastic osteosarcoma cells, UMR-106. Sp-cAMPS (10(-4)M), a direct activator of PKA, as well as dibutyryl cAMP (dbcAMP, 10(-4)M) significantly inhibited collagen synthesis. Human (h) PTH-(1-34) (10(-7)M) and hPTHrP (10(-7) M) inhibited collagen synthesis to the same degree. Although Rp-cAMPS, which acted directly as an antagonist in the activation of PKA, did not affect collagen synthesis by itself, it significantly antagonized dbcAMP- and Sp-cAMPS-induced inhibition of collagen synthesis. Moreover, Rp-cAMPS antagonized PTH- and PTHrP-induced inhibition of collagen synthesis to the same degree. The present study first indicated that the activation of PKA was directly linked to the regulation of collagen synthesis by PTH in osteoblast and that PTHrP had the same effect on collagen synthesis presumably through the same mechanism as PTH.
Kano
J
J
Department of Medicine Kobe University School of Medicine, Japan.
Sugimoto
T
T
Fukase
M
M
Chihara
K
K
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002460:Cell Line; D003094:Collagen / Q000096:biosynthesis*; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D015759:Ionomycin / Q000494:pharmacology; D007700:Kinetics; D010006:Osteoblasts; D012516:Osteosarcoma; D010281:Parathyroid Hormone / Q000494:pharmacology*; D044162:Parathyroid Hormone-Related Protein; D011392:Proline / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism*; D011506:Proteins / Q000494:pharmacology*; D051381:Rats; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013873:Thionucleotides / Q000494:pharmacology; D014316:Tritium
D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D011506:Proteins; D013873:Thionucleotides; D014316:Tritium; C016957:adenosine-3',5'-cyclic phosphorothioate; D000001:Calcimycin; D015759:Ionomycin; D003994:Bucladesine; D003094:Collagen; D011392:Proline; D000242:Cyclic AMP; D011494:Protein Kinases; D013755:Tetradecanoylphorbol Acetate