新型甲状旁腺素短肽水凝胶促进MSC分泌Ang-1募集“H型内皮细胞”参与骨重建的机制研究

新型甲状旁腺素短肽水凝胶具有类细胞外基质结构，可显著提高合成材料表面的黏附性和成骨效果，但是机制不明。优异的骨重建需要与血管形成偶联，共同实现骨修复，课题组研究显示新型水凝胶可促进共培养MSC分泌血管生成素-1（Ang-1），而后者已显示出在多种组织内具有促进新生血管的能力。骨重建中的内皮细胞为不同于其他组织的“H型内皮细胞”，Ang-1能否调节其迁移并形成血管完成骨修复并未可知。预实验提示MSC与新材料相互作用的上清液可提高H型内皮细胞的迁移和成血管能力，据此推测：新型修饰材料诱导MSC分泌Ang-1，通过Tie2-NOX4/mROS通路调节H型内皮细胞迁移和成血管，再与成骨祖细胞相互作用，完成骨重建。本课题立足于新型材料与MSC不同的作用方式，综合成骨与血管再生的效果筛选最佳方式，从血管形成的角度探索新型表面修饰材料的成骨机制，以特异的H型内皮细胞作为靶点，为骨修复机制研究提供新思路。

Due to its poor adhesivity and biocompatibility, the effect of artificial synthetic bone repair materials is not satisfactory. Novel modification materials fabricated by parathyrin short-peptide (Osteostatin) can significantly improve the surface adhesion and osteogenesis of synthetic materials while related mechanisms remain unclear. Past researches indicate highly coupled bone remodeling and vasculogenic could together repair damaged bones. Our group finds that the above-mentioned short-peptide could induce the co-cultured MSCs to secret Ang-1, and the latter has been proved to promote vasculogenesis in various tissues. Different from these in other tissues, endothelial cells during the bone remodeling progress belong to so-called “Type H endothelial cells”, and whether its migration can be regulated by Ang-1 to achieve vasculogenesis and bone remodeling remains unknown. Preliminary experiments showed, in the environment of novel modification materials, the MSC supernatant could enhance the migration and vasculogenesis of “Type H endothelial cells”. Therefore, it can be speculated that our new modification materials could induce the MSCs to secret Ang-1, regulate the migration and vasculogenesis of “Type H endothelial cells” through Tie2-NOX4/mROS pathway, and then interact with osteogenic progenitor cells to complete the bone remodeling process. From the perspective of vasculogenesis, our study explores the osteogenesis mechanisms of the new surface modification materials, and, by targeting bone-specific type H endothelial cells, provide novel ideas for the researches of bone repair mechanisms.