Effects of Osteoglycin (OGN) on treating senile osteoporosis by regulating MSCs.
Effects of Osteoglycin (OGN) on treating senile osteoporosis by regulating MSCs.
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DOI：
10.1186/s12891-017-1779-7
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发表时间：
2017-10-26
影响因子：
2.3
通讯作者：
Peng Y
中科院分区：
文献类型：
--
作者：
Chen X;Chen J;Xu D;Zhao S;Song H;Peng Y
在衰老过程中，由于骨髓微环境中成骨细胞介导的骨形成和破骨细胞介导的骨吸收失衡，导致大量骨量丢失，导致老年人群净骨丢失，从而导致骨质疏松症的发生。首先，观察小鼠骨髓间充质干细胞（MMSCs）和老年小鼠模型来源的骨髓间充质干细胞（SMMSCs）在脂肪细胞增殖和成脂分化能力以及OGN和PPARγ2 mRNA表达的差异。其次，观察经罗格列酮（一种过氧化物酶体增殖物激活物受体γ2激动剂）处理的MMSCs和SMMSCs的成骨能力，并评估过氧化物酶体增殖物受体γ2与OGN的负相关性。第三，通过增强OGN的表达，探讨SMMSCs促进成骨的作用，并通过相关脂肪细胞和成骨细胞特异性基因的表达，探讨SMMSCs促进成骨的机制。通过OGN感染的慢病毒强制OGN表达可增加Wnt5b、RUNX2、OCN、ALP和Colla1的表达以及骨形成，同时降低脂肪形成标志物PPARγ2的表达。其导致骨髓中脂肪细胞基因如脂肪细胞分化相关基因脂肪细胞结合蛋白2（aP2）和破骨细胞分化因子Rankl的表达抑制，从而引起骨量增加。OGN可能在骨质疏松症中发挥重要作用，也可能为以BMSCs向成骨细胞和脂肪细胞分化改变为特征的老年性骨质疏松症的治疗干预提供潜在靶点。
Significant amount of bone mass is lost during the process of aging due to an imbalance between osteoblast-mediated bone formation and osteoclast-mediated bone resorption in bone marrow microenvironment, which leads to net bone loss in the aging population, resulting in the pathogenesis of osteoporosis. Firstly, differences in proliferative capacity of adipocyte or adipogenic differentiation in mouse mesenchymal stem cells (MMSCs) and senile mouse model-derived bone marrow mesenchymal stem cells (SMMSCs), as well as mRNA expression of OGN and PPARγ2 were observed. Secondly, osteogenic abilities of MMSCs and SMMSCs treated with rosiglitazone (a PPARγ2 agonist) to induce osteogenic changes were observed, and negative correlation of PPARγ2 with OGN was evaluated. Thirdly, the role of SMMSCs in promoting osteogenesis was examined through enhancing expression of OGN; besides, the related mechanism was investigated by means of expression of related adipocyte and osteoblast specific genes. Forced OGN expression by OGN-infected lentivirus could increase expression of Wnt5b, RUNX2, OCN, ALP and Colla1, as well as bone formation, while decreases expression of adipogenesis marker PPARγ2. It resulted in expression inhibition of adipocyte genes such as adipocytic differentiation related genes adipocyte binding protein 2 (aP2) and osteoclast differentiation factor Rankl in bone marrow, giving rise to increased bone mass. OGN may plays a significant role in osteoporosis, which may also provide a potential target for therapeutic intervention of senile osteoporosis characterized by altered differentiation of BMSCs into osteoblasts and adipocytes.
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