Bap/avβ6/TLR-4信号调控成骨细胞骨生成在骨髓炎中的作用及机制研究

骨髓炎大多以细菌生物膜形态致病，故探讨其主要致病菌S.aureus生物膜在骨生成中的作用更接近临床实际。我们前期用S.aureus生物膜相关蛋白（Bap）处理成骨细胞后，αvβ6蛋白水平下降，TLR-4及TLR-2表达增强，而RUNX-2与ALP成骨基因下调；但抑制αvβ6后，TLR-4及TLR-2表达仍上调，RUNX-2与ALP环比有所上调，表明αvβ6、TLR-4及TLR-2可能参该过程调控。此外，前期课题发现WNT、TNF-α不同信号交互参与了骨生成的调控过程。进而，我们通过生物信息学分析，发现成骨细胞启动子区域存在与Bap的结合位点。由此我们推测：S.aureus细菌膜通过与αvβ6连接，促进Bap结合TLR-4与TLR-2，调控WNT、TNF-α不同信号影响成骨过程。本研究拟将细菌膜的Bap作为研究对象，从新角度阐明骨髓炎骨再生的机制，以期提供理论依据和新思路。

Osteomylitis are commonly caused by bacterial film, so investigation the role of the main pathogenic bacterium, S.aureus bacterial film, in the bone formation course is closer to the clinical practice. In earlier stage, we treated osteoblasts with S.aureus biofilm, and found αvβ6 protein level declines and TLR-4 and TLR-2 were enhanced, but RUNX-2 and ALP genes expression also decline. Whereas, suppression αvβ6, TLR-4 and TLR-2 were also enhanced, RUNX-2 and ALP increased at an annual rate. All these indicates αvβ6、TLR-4 and TLR-2 might involved in this regulation process. Then, we found a binding site at promoter region in osteoblasts, which may bond Bap. Thus, we speculates that S.aureus bacterial film promotes the bonding between Bap and TLR-4 and TLR-2 by connecting with αvβ6, that regulates the bone formation process influenced with WNT、TNF-α different signals. This research plants to illuminate the mechanism of bone formation in osteomyelitis from new standpoint by taking Bap as the research object, expecting to providing theory base and new thought.