Vitamin D and growth hormone regulate growth hormone/insulin-like growth factor (GH-IGF) axis gene expression in human fetal epiphyseal chondrocytes

被引：21

作者：

Fernandez-Cancio, M. ^{[1
]}

Audi, L. ^{[1
]}

Carrascosa, A. ^{[1
]}

Toran, N. ^{[2
]}

Andaluz, P. ^{[1
]}

Esteban, C. ^{[1
]}

Granada, M. L. ^{[3
]}

机构：

[1] Autonomous Univ Barcelona, Hosp Vall dHebron, Pediat Endocrinol Res Unit,Inst Salud Carlos 3, Res Inst,CIBERER Ctr Invest Red Enfermedades Rara, Barcelona, Spain

[2] CIBERER, Hosp Vail dHebron, Dept Pathol, Barcelona, Spain

[3] Hosp Germans Trias Pujol, Hormonal Lab, Barcelona, Spain

来源：

GROWTH HORMONE & IGF RESEARCH | 2009年 / 19卷 / 03期

关键词：

IGF-I; Human growth plate chondrocytes; Gene expression; Vitamin D; Growth hormone; MESSENGER-RIBONUCLEIC-ACID; FACTOR BINDING PROTEIN-3; OSTEOBLAST-LIKE CELLS; FACTOR-I; DIFFERENTIAL REGULATION; PARATHYROID-HORMONE; PLATE CHONDROCYTES; RAT CHONDROCYTES; PRIMARY CULTURE; PROLIFERATION;

D O I：

10.1016/j.ghir.2008.10.004

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

Objective: Cell 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 D-3 (VitD) and growth hormone (GH). Design: Chondrocytes 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 H-3-thymidine incorporation into DNA and IGF-I, IMP-3, GHR, SOX9, COL2A1, aggrecan and COMP gene expression by real-time quantitative PCR. Results: VitD dose-dependently and significantly inhibited H-3-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). Conclusions: Our 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. (C) 2008 Elsevier Ltd. All rights reserved.

引用

页码：232 / 237

页数：6

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