Association of increased intracellular free Ca2+ by platelet-derived growth factor with mitogenesis but not with proteoglycan synthesis in chondrocytes--effect of suramin.
The effects of platelet-derived growth factor (PDGF) on the intracellular free Ca2+ concentration [( Ca2+]i) in chondrocytes were studied with a fluorescent Ca2+ indicator, fura 2, and compared with the effects of PDGF on mitogenesis and proteoglycan synthesis. PDGF evoked phasic and then tonic increase in [Ca2+]i dose-dependently in quiescent cultures of chondrocytes, and it also stimulated both DNA and proteoglycan syntheses dose-dependently similar to somatomedins. Suramin, which inhibits the interaction of PDGF with its receptors, caused dose-dependent inhibition of both the PDGF-evoked increase in [Ca2+]i and stimulation of DNA synthesis by PDGF. However, suramin rather enhanced the proteoglycan synthesis induced by PDGF without affecting the basal level of proteoglycan synthesis directly. These results suggest that [Ca2+]i may be an important signal for the action of PDGF on cell proliferation in chondrocytes, and that the initial signal for proteoglycan synthesis is different from that for DNA synthesis induced by PDGF after the activation of PDGF receptor.
Fukuo
K
K
Department of Medicine and Geriatrics, Osaka University Medical School, Japan.
Morimoto
S
S
Kaji
K
K
Koh
E
E
Hironaka
T
T
Morita
R
R
Kim
S
S
Onishi
T
T
D000818:Animals; D001572:Benzofurans; D002118:Calcium / Q000378:metabolism*; D002356:Cartilage / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D003592:Cytophotometry; D016257:Fura-2; D008297:Male; D008938:Mitosis / Q000187:drug effects*; D010982:Platelet-Derived Growth Factor / Q000378:metabolism / Q000494:pharmacology*; D011509:Proteoglycans / Q000096:biosynthesis*; D011817:Rabbits; D011956:Receptors, Cell Surface / Q000378:metabolism; D017479:Receptors, Platelet-Derived Growth Factor; D013498:Suramin / Q000494:pharmacology*
D001572:Benzofurans; D010982:Platelet-Derived Growth Factor; D011509:Proteoglycans; D011956:Receptors, Cell Surface; D013498:Suramin; D017479:Receptors, Platelet-Derived Growth Factor; D002118:Calcium; D016257:Fura-2