Insulin like growth factor-I, protein kinase-C, calcium and cyclic AMP: partners in the regulation of chondrocyte mitogenesis and metabolism.
The possible role of protein kinase-C (PKC), calcium and cyclic AMP (cAMP) in mediating the metabolic and mitogenic effects of insulin-like growth factor-I (IGF-I) on chondrocytes was investigated using a PKC activator (phorbol ester 12,13-dibutyrate, PDBU), a PKC inhibitor (compound H7), a calcium channel blocker, (verapamil) and a cAMP analogue (dibutyryl cAMP). IGF-I and PDBU stimulated sulphate and thymidine incorporation by chondrocytes. Both of these effects were inhibited by compound H7. Verapamil inhibited IGF-I- and PDBU-stimulated sulphate incorporation, but contrastingly stimulated basal and enhanced IGF-I and PDBU stimulation of thymidine incorporation. Dibutyryl cAMP increased basal and IGF-I-stimulated sulphate incorporation but inhibited but inhibited both basal and IGF-I stimulation of thymidine incorporation. These results suggest a harmonic overlap between the activities of PKC and cAMP-dependent PKA enzyme systems, and calcium balance in the mitogenic and metabolic process of the chondrocyte.
Taylor
A M
AM
Department of Growth and Development, Institute of Child Health, London, England.
Dandona
P
P
Morrell
D J
DJ
Preece
M A
MA
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D002358:Cartilage, Articular / Q000166:cytology* / Q000378:metabolism; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000502:physiology*; D007546:Isoquinolines / Q000494:pharmacology; D008938:Mitosis; D015240:Phorbol 12,13-Dibutyrate; D010703:Phorbol Esters / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D013002:Somatomedins / Q000502:physiology*; D013552:Swine; D014700:Verapamil / Q000494:pharmacology
D007546:Isoquinolines; D010703:Phorbol Esters; D010879:Piperazines; D013002:Somatomedins; D015240:Phorbol 12,13-Dibutyrate; D003994:Bucladesine; D007334:Insulin-Like Growth Factor I; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D014700:Verapamil; D000242:Cyclic AMP; D011493:Protein Kinase C; D002118:Calcium