Osteoporosis and obesity: Role of Wnt pathway in human and murine models
Osteoporosis and obesity: Role of Wnt pathway in human and murine models
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DOI：
10.5312/wjo.v5.i3.242
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发表时间：
2014-07-18
影响因子：
1.9
通讯作者：
Grano, Maria
中科院分区：
文献类型：
--
作者：
Colaianni, Graziana;Brunetti, Giacomina;Grano, Maria
关于肥胖和骨质疏松症之间的病理生理学联系的研究目前是一个有趣的研究领域。虽然这两种疾病的发病方式不同，但最近的研究表明，肥胖和骨质疏松症有着共同的遗传和环境因素。尽管肥胖是健康的危险因素，但传统上认为肥胖对骨是积极的，因为高体重对骨形成施加的机械负荷的有益作用。然而，对比研究尚未达成明确的共识，相反，肥胖症导致的过量脂肪可能无法预防骨质疏松症，甚至更糟的是，可能对骨骼有害。另一方面，迄今为止更好地确定，由于脂肪细胞和成骨细胞来源于共同的间充质干细胞前体，导致成骨细胞生成的分子抑制脂肪生成，反之亦然。在这里，我们将讨论的关键分子调节脂肪细胞和成骨细胞分化，这是过氧化物酶体增殖物激活受体γ和Wnt的作用，分别。特别是，我们将集中在经典和非经典的Wnt信号的作用，参与间充质细胞的命运调控。此外，目前还没有实验数据表明Wnt抑制剂Sclerostin对脂肪形成的任何影响，尽管众所周知其对骨代谢的作用。此外，最常见的病理条件，其中有一个同时增加的肥胖和减少的骨量是更年期。考虑到绝经后妇女的硬化蛋白水平与循环雌二醇水平呈负相关，并且由于性激素替代疗法已被证明可有效减轻骨丢失和逆转绝经相关肥胖，我们假设硬化蛋白在脂肪形成中的作用可能是未来几年的研究重点。(C)2014百世登出版集团股份有限公司All rights reserved.
Studies concerning the pathophysiological connection between obesity and osteoporosis are currently an intriguing area of research. Although the onset of these two diseases can occur in a different way, recent studies have shown that obesity and osteoporosis share common genetic and environmental factors. Despite being a risk factor for health, obesity has traditionally been considered positive to bone because of beneficial effect of mechanical loading, exerted by high body mass, on bone formation. However, contrasting studies have not achieved a clear consensus, suggesting instead that excessive fat mass derived from obesity condition may not protect against osteoporosis or, even worse, could be rather detrimental to bone. On the other hand, it is hitherto better established that, since adipocytes and osteoblasts are derived from a common mesenchymal stem cell precursor, molecules that lead to osteoblastogenesis inhibit adipogenesis and vice versa. Here we will discuss the role of the key molecules regulating adipocytes and osteoblasts differentiation, which are peroxisome proliferators activated receptor-gamma and Wnts, respectively. In particular, we will focus on the role of both canonical and non-canonical Wnt signalling, involved in mesenchymal cell fate regulation. Moreover, at present there are no experimental data that relate any influence of the Wnt inhibitor Sclerostin to adipogenesis, although it is well known its role on bone metabolism. In addition, the most common pathological condition in which there is a simultaneous increase of adiposity and decrease of bone mass is menopause. Given that postmenopausal women have high Sclerostin level inversely associated with circulating estradiol level and since the sex hormone replacement therapy has proved to be effective in attenuating bone loss and reversing menopause-related obesity, we hypothesize that Sclerostin contribution in adipogenesis could be an active focus of research in the coming years. (C) 2014 Baishideng Publishing Group Inc. All rights reserved.