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脂联素通过 Wnt/β-连环蛋白通路调节骨髓间充质干细胞的成骨分化和骨生成。

Adiponectin regulates BMSC osteogenic differentiation and osteogenesis through the Wnt/β-catenin pathway.

机构信息

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, People's Republic of China.

Department of Stomatology, Guangzhou Hospital of Integrated Traditional and Western Medicine, Guangzhou, 510800, People's Republic of China.

出版信息

Sci Rep. 2017 Jun 16;7(1):3652. doi: 10.1038/s41598-017-03899-z.

Abstract

Recent studies have demonstrated the stimulatory effects of adiponectin on bone formation, but the mechanism underlying these effects remains unclear. The Wnt/β-catenin pathway, one of the most important pathways in osteogenesis, has rarely been associated with the osteogenic effects of adiponectin in previous studies. The present study was designed to investigate the effects of adiponectin on bone mesenchymal stem cell (BMSC) osteogenic differentiation and bone formation through the Wnt/β-catenin pathway. We detected adiponectin receptor expression in BMSCs, constructed a recombinant adenovirus containing the human adiponectin gene, and then used the adenovirus to transfect BMSCs in vitro or injected the adenovirus into bone defect areas in animal models. Wnt/β-catenin pathway and osteogenesis were detected by real-time PCR, western blotting, immunofluorescence, HE staining and micro-CT. In both our in vivo and in vitro experiments, we detected higher gene and protein expression levels of the Wnt/β-catenin pathway-related factors β-catenin and cyclinD1 in adiponectin transgenic BMSCs and rats. Similar results were noted regarding the gene and protein expression levels of osteogenesis-related genes. In addition, more new bone formation was observed in the adiponectin-treated groups. Our results indicate that adiponectin could facilitate BMSC osteogenic differentiation and osteogenesis, and the Wnt/β-catenin pathway was involved in the osteogenic effect of adiponectin.

摘要

最近的研究表明脂联素对骨形成具有刺激作用,但这些作用的机制尚不清楚。Wnt/β-catenin 通路是成骨过程中最重要的通路之一,在之前的研究中,很少有研究将其与脂联素的成骨作用联系起来。本研究旨在通过 Wnt/β-catenin 通路探讨脂联素对骨髓间充质干细胞(BMSC)成骨分化和骨形成的影响。我们检测了 BMSCs 中脂联素受体的表达,构建了含有人脂联素基因的重组腺病毒,然后用腺病毒在体外转染 BMSCs 或在动物模型中注射腺病毒到骨缺损部位。通过实时 PCR、western blot、免疫荧光、HE 染色和 micro-CT 检测 Wnt/β-catenin 通路和成骨作用。在我们的体内和体外实验中,我们检测到转染了脂联素的 BMSCs 和大鼠中 Wnt/β-catenin 通路相关因子β-catenin 和 cyclinD1 的基因和蛋白表达水平更高。骨形成相关基因的基因和蛋白表达水平也有类似的结果。此外,在脂联素处理组中观察到更多的新骨形成。我们的结果表明,脂联素可以促进 BMSC 成骨分化和骨形成,Wnt/β-catenin 通路参与了脂联素的成骨作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6fc/5473871/747b96348846/41598_2017_3899_Fig1_HTML.jpg

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