炎症因子IL-6通过调节BMP受体的表达影响BMP-2诱导骨再生的机制

使用成骨诱导因子BMP-2和可吸收胶原海绵制作的骨移植替代物（BMP-2/ACS）已被批准用于临床促进骨再生，修复骨缺损。然而项目组前期研究证实炎症环境通过抑制骨生成和促进骨吸收的方式抑制BMP-2/ACS诱导的骨再生。虽然IL-6在炎症环境中表达显著增高，但预实验发现IL-6在体外促进BMP-2诱导BMSC成骨分化。因此，为研究IL-6对BMP-2诱导骨再生的影响，本项目拟通过构建BMP-2/ACS诱导大鼠皮下异位成骨的动物模型，并采用IL-6细胞因子注射提高体内IL-6浓度，研究IL-6对BMP-2/ACS诱导骨再生的作用。接着以BMP/Smad通路为切入点，分析IL-6对三个BMP受体表达、转位和降解的影响，探究IL-6如何调控BMP/Smad通路的激活，以及对BMSC成骨分化的影响，进一步阐明IL-6影响BMP-2诱导骨再生的机制，为提高BMP-2体内成骨诱导效率提供新的思路。

Bone grafts made by biomaterials and growth factors, such as INFUSE® Bone Graft (BMP-2/ACS), have been approved for clinical use in in specific clinical scenarios to enhance bone regeneration. However, our previous study have proved that the inflammatory environment decreased BMP-2/ACS-induced ectopic bone mass by suppressing BMP-2-induced osteoblastic differentiation and by increasing the number or activity of osteoclasts. Our pilot experiment have found that IL-6 also significantly elevated in the inflammatory environment, however, IL-6 showed a positive effect on BMP-2-induced osteogenic differentiation of BMSCs. Therefore, based on these results, we planning to construct a BMP-2/ACS-induced ectopic bone formation model in rats and elevate the concentration of IL-6 in the rat by IL-6 injection subcutaneously for investigation the role of elevated IL-6 on BMP-2/ACS-induced bone formation. Then, with the key point of BMP-2-mediated BMP/Smad signaling pathway, we going to analysis the role of IL-6 on expression, cell surface translocation, and degradation of BMPRIA, BMPRIB, and BMPRII in BMSCs, and investigate how IL-6 regulate the activation of BMP-2/Smad signaling and the effect on osteogenic differentiation of BMSCs. After this study, we hope the results could help us for understanding the role of inflammatory environment on BMP-2-induced bone regeneration and looking for a new way for improving the osteoinductive efficacy of BMP-2 in vivo.