کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2803049 | 1156720 | 2009 | 6 صفحه PDF | دانلود رایگان |
ObjectiveCell proliferation and gene expression regulation were studied in human fetal epiphyseal chondrocytes to ascertain the involvement of GH–IGF axis components in human fetal growth regulation by 1,25-dihydroxyvitamin D3 (VitD) and growth hormone (GH).DesignChondrocytes from primary cultures were plated in serum-free medium for 48 h and incubated for a further 48 h with VitD (10−11 to 10−6 M) and/or IGF-I (100 ng/ml) and/or GH (500 ng/ml). We analyzed 3H-thymidine incorporation into DNA and IGF-I, IGFBP-3, GHR, SOX9, COL2A1, aggrecan and COMP gene expression by real-time quantitative PCR.ResultsVitD dose-dependently and significantly inhibited 3H-thymidine incorporation whereas GH had no effect on proliferation and, when combined with VitD, the same inhibition was observed as with VitD alone. IGF-I (100 ng/ml) significantly stimulated proliferation and opposed inhibition by VitD. VitD dose-dependently stimulated IGF-I (11.1 ± 19.8 at VitD 10−6 M), IGFBP-3 (2.6 ± 0.9), GHR (3.8 ± 2.8) and COMP (1.5 ± 0.6) expression whereas it inhibited SOX9 (0.7 ± 0.2), COL2A1 (0.6 ± 0.3) and aggrecan (0.6 ± 0.2) expression and had no significant effect on IGF-II. IGF-I stimulated IGF-I, IGFBP-3, SOX9, COL2A1 and aggrecan expression and opposed COL2A1 and aggrecan gene expression inhibition by VitD. GH alone had no effect on gene expression whereas, in the presence of VitD, significantly-increased IGF-I expression stimulation was observed above values obtained with VitD alone (17.5 ± 7.4).ConclusionsOur results suggest that VitD regulation of fetal growth cartilage could have consisted of parallel enhancing of cell differentiation and conditioning to a phenotype more sensitive to regulation by other hormones such as GH as shown by increased GHR and IGF-I expression, but not by IGF-II expression which was not regulated.
Journal: Growth Hormone & IGF Research - Volume 19, Issue 3, June 2009, Pages 232–237