p38MAPK/PGC-1α激活线粒体能量代谢在SrBG促进衰老巨噬细胞免疫调控成骨中的机制研究

衰老巨噬细胞由于线粒体功能障碍，免疫调控成骨能力降低，严重影响骨缺损的愈合。目前研究表明，通过增强线粒体能量代谢可恢复衰老巨噬细胞的正常生理功能。但锶掺杂生物活性玻璃（SrBG）是否具有这样的能力尚未见报道。申请人前期研究发现，SrBG能增强衰老巨噬细胞免疫调控成骨相关因子的释放。进一步预实验发现，SrBG可上调衰老巨噬细胞内线粒体生物合成关键蛋白PGC-1α的表达，伴随能量水平升高。p38 MAPK作为PGC-1α的重要上游调控蛋白，抑制其表达后，PGC-1α表达及能量水平均明显降低，且调控成骨相关因子的释放减少。因此提出以下科学假说：SrBG通过激活p38 MAPK/PGC-1α增强线粒体能量代谢，促进衰老巨噬细胞的骨免疫调控能力。本项目拟利用免疫组化、慢病毒转染等技术手段，阐明SrBG促进衰老巨噬细胞免疫调控成骨中的作用机制。本研究将为老年骨缺损的治疗提供新思路。

The immunoregulation osteogenesis of aged macrophages will decreased as mitochondrial dysfunction, which significantly affects the healing of bone defects. Current researches suggest that the normal physiological function of aged macrophages can be recovered by enhancing mitochondria energy metabolism. However, it has not been reported whether strontium droped bioactive glasses (SrBG) has the ability. The preliminary studies of the applicant find that SrBG can enhance the release of osteogenesis related factors of aging macrophages. Further preliminary experiment find that the expression of PGC-1α is significantly up-regulated in aging macrophages with the influence of SrBG, which the energy level is also increased. After suppressing expression of p38 MAPK, both the expression of PGC-1α and the energy level are significantly decrease, as p38 MAPK is an important upstream regulatory protein of PGC-1α. Therefore the scientific hypothesis is presented: SrBG promotion aged macrophages immunoregulation of osteogenesis by p38 MAPK/PGC-1α activation mitochondria energy metabolism. This project will illuminate the mechanism of SrBG promotes aged macrophage immunoregulation of osteogenesis by using the methods of immunohistochemistry, lentiviral transfection and so on. This study will provide new ideas for the treatment of aging bone defects.