Chen Xia, Chen Junsong, Xu Dongliang, Zhao Shuangxia, Song Huaidong, Peng Yongde
Department of Endocrinology and Metabolism, Shanghai General Hospital of Nanjing Medical University, 100 Haining Road, Shanghai, 200080, China.
Key Laboratory of Systems Biomedicine(Ministry of Education), Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai, 200240, China.
BMC Musculoskelet Disord. 2017 Oct 26;18(1):423. doi: 10.1186/s12891-017-1779-7.
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.
在衰老过程中，由于骨髓微环境中破骨细胞介导的骨吸收与成骨细胞介导的骨形成之间失衡，大量骨量流失，这导致老年人群出现净骨丢失，进而引发骨质疏松症的发病机制。
首先，观察小鼠间充质干细胞（MMSCs）和老年小鼠模型来源的骨髓间充质干细胞（SMMSCs）中脂肪细胞增殖能力或成脂分化的差异，以及OGN和PPARγ2的mRNA表达。其次，观察用罗格列酮（一种PPARγ2激动剂）处理MMSCs和SMMSCs以诱导成骨变化的成骨能力，并评估PPARγ2与OGN的负相关性。第三，通过增强OGN的表达来研究SMMSCs在促进成骨中的作用；此外，通过相关脂肪细胞和成骨细胞特异性基因的表达来研究其相关机制。
通过OGN感染的慢病毒强制表达OGN可增加Wnt5b、RUNX2、OCN、ALP和Colla1的表达以及骨形成，同时降低脂肪生成标志物PPARγ2的表达。这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的表达受到抑制，从而增加骨量。
OGN可能在骨质疏松症中起重要作用，这也可能为以骨髓间充质干细胞向成骨细胞和脂肪细胞分化改变为特征的老年骨质疏松症的治疗干预提供潜在靶点。
