Effect of adiponectin on ATDC5 proliferation, differentiation and signaling pathways
Effect of adiponectin on ATDC5 proliferation, differentiation and signaling pathways
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DOI：
10.1016/j.mce.2010.03.025
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发表时间：
2010-07-29
影响因子：
4.1
通讯作者：
Ornan, E. Monsonego
中科院分区：
文献类型：
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作者：
Challa, T. Delessa;Rais, Y.;Ornan, E. Monsonego
脂联素是一种脂肪分泌的脂肪细胞因子，具有多种代谢功能，但尚不清楚通过生长板对骨发育的影响，尤其是在软骨细胞中。以体外培养的小鼠ATDC5细胞为模型，研究了脂联素及其受体在软骨分化过程中的表达。0.5mU g/ml的脂联素促进软骨细胞增殖、蛋白多糖合成和基质矿化，表现为上调II型胶原、蛋白多糖、Runx2和X型胶原的表达以及碱性磷酸酶的活性。定量逆转录聚合酶链式反应和明胶酶谱分析显示，脂联素治疗后基质金属蛋白酶MMP9‘S的表达和活性显著增加。因此，我们认为脂联素可以直接刺激软骨细胞的增殖和分化。为了评估其潜在的机制，我们研究了脂联素对成软骨信号分子IHH、PTHrP表达的影响。Ptc1、FGF18、BMP7、IGF1和p21表达上调，FGF9表达下调。本研究揭示了脂联素在软骨细胞中的新的直接活性，提示其对骨发育有积极作用。(C)2010爱思唯尔爱尔兰有限公司。保留所有权利。
Adiponectin, an adipose-secreted adipocytokine, exhibits various metabolic functions but has no known effect on bone development through the growth plate and specifically, in chondrocytes. Using the mouse ATDC5 cell line, a widely used in vitro model of chondrogenesis, we demonstrated the expression of adiponectin and its receptors during chondrogenic differentiation. Adiponectin at 0.5 mu g/ml increased chondrocyte proliferation, proteoglycan synthesis and matrix mineralization, as reflected by upregulation of the expression of type II collagen, aggrecan, Runx2 and type X collagen, and of alkaline phosphatase activity. Quantitative RT-PCR and gelatin zymography showed a significant increase in the matrix metalloproteinase MMP9's expression and activity following adiponectin treatment. We therefore concluded that adiponectin can directly stimulate chondrocyte proliferation and differentiation. To evaluate the underlying mechanisms, we examined the effect of adiponectin on the expression of chondrogenic signaling molecules: Ihh, PTHrP. Ptc1, FGF18, BMP7, IGF1 and p21 were all upregulated while FGF9 was downregulated. This study reveals novel and direct activity of adiponectin in chondrocytes, suggesting its positive effects on bone development. (C) 2010 Elsevier Ireland Ltd. All rights reserved.