Sdccag3通过Wnt通路对高脂血症大鼠种植体骨结合的影响

doi:10.6040/j.issn.1671-7554.0.2022.0183

摘要/Abstract

摘要： 目的探讨Sdccag3在高脂环境中通过Wnt信号通路影响骨髓间充质干细胞(BMSCs)成脂成骨分化以及高脂血症大鼠种植体周围骨结合的能力。方法构建高脂血症大鼠模型以及高脂环境培养BMSCs并进行成骨诱导,慢病毒载体过表达/沉默结肠癌抗原3(Sdccag3)的表达,采用RT-PCR、Western blotting、Micro-CT以及硬组织切片HE染色、油红O染色、免疫荧光染色等方法检测高脂环境中Sdccag3对大鼠骨代谢以及BMSCs分化平衡的影响。结果高脂成骨诱导BMSCs后过表达Sdccag3,下调成脂分化指标脂肪酸结合蛋白4(FABP4)、过氧化物酶体增殖剂激活受体γ(PPAR-γ),并上调Wnt信号通路标志基因低密度脂蛋白受体相关蛋白 5(LRP5)、LRP6、β-catenin及Wnt5a、Wnt5b,上调成骨分化指标碱性磷酸酶(ALP)、 Runt相关的转录因子2(Runx2);在高脂血症大鼠种植体周围骨组织中,过表达Sdccag3可上调Wnt信号通路标志基因并抑制周围脂形成,沉默LRP5会下调Sdccag3、成骨分化指标,上调成脂分化指标,与沉默Sdccag3表达一致。结论高脂血症促进种植体周围脂肪形成并抑制Sdccag3表达;过表达Sdccag3抑制BMSCs成脂分化并降低高脂血症大鼠种植体周围的成脂,促进成骨,促进Wnt信号通路标志基因表达。

关键词: 高脂血症, Sdccag3, 成脂分化, Wnt通路, 低密度脂蛋白受体相关蛋白 5

Abstract: Objective To investigate the effects of serologically defined colon cancer antigen-3(Sdccag3)on the differentiation of bone marrow mesenchymal stem cells(BMSCs)and the osteointegration around implants in hyperlipidemia rats through Wnt signaling pathway in high lipid environment. Methods BMSCs were cultured in hyperlipidemia rat models and induced by high lipid environment. Sdccag3 expression was overexpressed/silenced by lentivirus vector. RT-PCR, Western blotting, Micro-CT, HE staining, Oil red O staining and immunofluorescence staining were used to assess the effects of high lipid environment and Sdccag3 on bone metabolism and BMSCs differentiation balance. Results Sdccag3 was overexpressed in BMSCs induced by high lipid osteogenesis, which inhibited lipid differentiation indexes peroxisome proliferators-activated receptors γ(FABP4)and peroxisome proliferators-activated receptors γ(PPAR-γ), up-regulated Wnt signaling pathway marker genes low density lipoprotein receptor-related protein 5(LRP5), low density lipoprotein receptor-related protein 6(LRP6), β-catenin, Wnt family member 5a(Wnt5a)and Wnt family member 5b(Wnt5b), and promoted osteogenic differentiation indexes alkaline phosphatase(ALP)and runt-related transcription factor 2(Runx2). In hyperlipidemia rats, overexpression of Sdccag3 up-regulated Wnt signaling pathway marker genes and inhibited peripheral lipid formation, while silencing LRP5 down-regulated Sdccag3, inhibited osteogenic differentiation and promoted lipid differentiation, which were consistent with silencing Sdccag3 expression. Conclusion Hyperlipidemia inhibits Sdccag3 expression. Overexpression of Sdccag3 inhibits adipogenic differentiation of BMSCs and decreases lipid formation around the implants in hyperlipidemia rats, promotes osteogenesis and expression of Wnt signaling pathway marker genes.

Key words: Hyperlipidemia, Sdccag3, Adipogenesis, Wnt pathway, Low density lipoprotein receptor-related protein 5

中图分类号:

R783

袁孟绮,霍凤蕾,任会萍,郭秋爽,蓝菁. Sdccag3通过Wnt通路对高脂血症大鼠种植体骨结合的影响[J]. 山东大学学报 (医学版), 2022, 60(7): 66-73.

YUAN Mengqi, HUO Fenglei, REN Huiping, GUO Qiushuang, LAN Jing. Effects of Sdccag3 on the osseointegration in hyperlipidemia rats through Wnt pathway[J]. Journal of Shandong University (Health Sciences), 2022, 60(7): 66-73.

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