[Autocrine regulation of cell proliferation and secretion of insulin-like growth factor I (IGF-I) in osteoblastic cell line MC3T3-E1].
Bone cells maintained in culture produce different growth factors which modulate cell growth via a mechanism of auto/paracrine regulation. IGF-1 is abundantly produced by murine bone cells where it acts as a mitogenic agent. The aim of this work was to study the effect of IGF-II, TGF beta 1, basic FGF (FGFb) and PDGF on cell growth and production of IGF-1 in the murine osteoblastic clonal cell line MC3T3-E1. IGF-1 was assayed by RIA after elimination of the IGF binding proteins. After 24th of treatment in culture conditions without serum, incorporation of [3H] methylthymidine increased significantly in MC3T3-E1 treated with IGF-II, FGFb and PDGF. The effect was dose-dependent. At low cell density (2.5 X 10(4) cemm/cm2) and after 24 h treatment, IGF-II at 10 ng/ml led to a 220% increase in IGF-I production in MC3T3-E1 cells (9.5 +/- 1.5 vs 4.2 +/- 0.44 ng/micrograms protein, p < 0.001) while TGF beta 1, FGFb and PDGF at 1 ng/ml led to a significant decrease (65, 95 and 85% respectively) in IGF-I (TGF beta 1: 1.5 +/- 0.3 ng/micrograms; FGBb: 0.21 +/- 0.04 ng/micrograms; PDGF: 0.66 +/- 0.1 ng/micrograms; p < 0.001). Production of IGF-I was controlled by a dose-dependent relationship and varied as a function of incubation time and cell density. IGF-II led to an increase in mRNA coding for IGF-1 as early as the first hour after IGF-II addition with a maximal effect at 6 hours.(ABSTRACT TRUNCATED AT 250 WORDS)
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UF Maladies Osseuses et Métaboliques, Service d'Endocrinologie, CHU Purpan, Toulouse.
Mohan
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Baylink
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Ribot
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D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D005346:Fibroblast Growth Factors / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D007335:Insulin-Like Growth Factor II / Q000494:pharmacology; D051379:Mice; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D012333:RNA, Messenger / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D005346:Fibroblast Growth Factors; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II
Régulation autocrine de la prolifération cellulaire et de la sécrétion d'insulin-like growth factor-I (IGF-I) dans la lignée ostéoblastique MC3T3-E1.