Irisin在绝经后骨质疏松中的作用及分子机制研究

绝经后骨质疏松是严重危害妇女健康的常见骨代谢疾病，目前的防治药物各有利弊，在选择上有一定限制。Irisin是近期发现的主要由运动诱导分泌的激素，除在糖脂代谢平衡中起重要作用外，有研究报道注射irisin能增加皮质骨密度及骨量。我们在前两项骨代谢自然基金资助下进一步研究发现：irisin能通过MAPK信号通路促进成骨细胞增殖、分化和矿化；抑制破骨细胞功能，促进间充质干细胞向成骨分化，抑制脂肪分化，具促成骨效应。据此，我们设想：如果irisin在对糖脂代谢起作用的同时，对骨代谢确有积极作用，可能成为骨质疏松较为理想的药物。但目前irisin与绝经后骨质疏松的研究报道较少，确切功能和作用机制尚不清楚。本研究拟采用irisin敲除小鼠模型、irisin敲除去势小鼠模型、去势小鼠模型，研究irisin在绝经后骨代谢中的确切作用和分子机制，及其与雌激素的关系，为可能的临床应用提供可靠的基础理论依据。

Postmenopausal osteoporosis is one of the most common bone metabolic disease, which harm women's health seriously. Because the medicines used to prevent and treat postmenopausal osteoporosis have different advantages and disadvantages, there are certain limitations on their use. Irisin, a novel exercise- induced hormone, is mainly secreted by skeletal muscle in response to exercise. It has been found that irisin plays an important role in maintaining the balance of glucose and lipid metabolism. Moreover, it was reported that injection of irisin increased bone density and bone mass of cortical bone. Supported by our two previous funds of natural sciences, we did further investigation, and found that irisin could promote proliferation, differentiation and mineralization of osteoblast by activating MAPK pathway. And irisin could also inhibit the function of osteclast, as well as induce the osteogenic differentiation, while not adipocyte differentiation of mesenchyma stem cell. All of these showed that irisin had osteogenic effect. Based on above information and results, we imagine that, irisin might be an ideal medicine for osteoporosis, if it really had the positive effects on bone metabolism as well as it's benefit on glucose and lipid metabolism at the same time. However, the reports about irisin and postmenopausal osteoporosis are few up until now. And the exact function and mechanism of irisin on osteoporosis are unclear. Because of this, we plan to use irisin knockout mouse model, irisin knockout ovariectomized mice mode, and ovariectomized mice model to investigate the exact role of irisin, the molecular mechanisms and the relationship between irisin and estrogen in postmenopausal osteoporosis.