Role of Osteoprotegerin (OPG) in Bone Marrow Adipogenesis.
Role of Osteoprotegerin (OPG) in Bone Marrow Adipogenesis.
复制标题
骨保护素（OPG）在骨髓脂肪生成中的作用
DOI：
10.1159/000452580
复制
发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Sun Yao
中科院分区：
文献类型：
--
作者：
Zhang Lili;Liu Mengmeng;Zhou Xiaokang;Liu Yi;Jing Bo;Wang Xiaogang;Zhang Qi;Sun Yao
背景/目的：骨髓脂肪生成是骨老化的主要特征之一。骨髓间充质干细胞（BMMSCs）在老年宿主骨髓腔中倾向于分化为脂肪细胞而不是成骨细胞。衰老骨髓中脂肪细胞的形成机制和功能有待进一步研究。骨保护素（Osteoprotegerin， OPG）是肿瘤坏死因子受体（tumor necrosis factor receptor， TNFR）超家族成员，具有抑制破骨细胞活性的作用。我们发现Opg基因敲除小鼠骨髓中脂肪细胞数量增加。在这项研究中，我们研究了OPG在骨髓间充质干细胞分化和骨髓脂肪形成中的作用。方法：对不同年龄的Opg敲除（Opg- ko）和野生型（WT）小鼠骨组织进行组织学分析。体外培养小鼠骨髓间充质干细胞以评估其分化能力。结果：随着年龄的增长，WT小鼠骨髓中Opg的表达明显降低，而成脂特异性转录因子过氧化物酶体增殖物激活受体γ (Ppar-γ)的表达升高。Opg-KO小鼠骨髓中脂肪细胞在相对年轻时形成，且随着年龄的增长，脂肪细胞的数量急剧增加。与WT对照组相比，Opg-KO BMMSCs的成骨分化减弱，但成脂分化增强。此外，外源OPG在体外可抑制OPG - ko BMMSCs的成脂分化，促进其成骨分化。结论：OPG在调节骨髓间充质干细胞分化和骨髓脂肪形成中起重要作用。
Background/Aims: Bone marrow adipogenesis is one of the major characteristics of aged bone. Bone marrow mesenchymal stem cells (BMMSCs) prefer to differentiate into adipocytes instead of osteoblasts in the bone marrow cavity in aged hosts. The mechanism of formation and function of adipocytes in aged bone marrow needs further investigation. Osteoprotegerin (OPG) is a member of the tumor necrosis factor receptor (TNFR) super family, and it can inhibit the activities of osteoclasts. We found that adipocyte numbers increased in the bone marrow of Opg knockout mice. In this study, we investigated the role of OPG in the differentiation of BMMSCs and bone marrow adipogenesis. Methods: Histological analyses were performed on the bone tissues of Opg knockout (Opg-KO) and wild-type (WT) mice of different ages. BMMSCs obtained from mice were cultured in vitro to evaluate their differentiation abilities. Results: With aging, the expression of Opg in the bone marrow of WT mice markedly decreased, but that of the adipogenic specific transcription factor peroxisome proliferator-activated receptor γ (Ppar-γ) increased. Adipocytes formed in the bone marrow of Opg-KO mice at a relative young age, and the number of adipocytes increased dramatically with age. Compared with the WT control, the osteogenic differentiation of Opg-KO BMMSCs decreased, but the adipogenic differentiation increased. Moreover, exogenous OPG could inhibit the adipogenic differentiation and promote the osteogenic differentiation of Opg-KO BMMSCs in vitro. Conclusions: OPG plays an important role in regulating BMMSC differentiation and bone marrow adipogenesis.