SDF-1/CXCR4介导的PI3K/Akt信号通路对巨噬细胞调控牙髓新生组织细胞外基质的作用机制

获得功能完整的牙髓组织是治疗牙髓病和根尖周病的最终目标，牙髓再生性治疗所面临的挑战之一是诱导形成的新生组织中含有大量的骨样/矿化组织。组织再生过程中对细胞外基质（ECM）的适当调控可以减少瘢痕和促进功能组织的形成，巨噬细胞是ECM分解、成纤维细胞激活的重要调控因素。我们前期的研究结果显示：SDF-1可以明显改善新生“牙髓”组织的组织构成，胶原纤维排列疏松而较为有序，矿化组织减少，巨噬细胞聚集，根据mRNA差异表达研究的结果，推测PI3K/Akt通路在巨噬细胞极化过程中起重要作用。因此，我们设想SDF-1/PI3K/Akt通路通过对巨噬细胞极化的调控，可降解过度形成的血管和ECM，减少骨样/矿化组织的形成。本研究将通过体内外实验探讨SDF-1/PI3K/Akt对巨噬细胞募集和极化的作用机制以及不同亚型巨噬细胞对ECM重构的影响，为改善牙髓新生组织的组织学构成提供科学依据。

Regeneration of functional dental pulp tissue is the ultimate goal for the treatment of endodontic disease and periapical disease. One of the challenges facing by dental pulp regenerative treatment is that the bone-like / mineralized tissue was induced in the regenerated tissue. Proper regulation of extracellular matrix (ECM) during tissue regeneration can reduce scars and promote the formation of functional tissues. Macrophages are important regulatory factors for ECM breakdown and fibroblast activation. Our previous research results show that SDF-1 can significantly improve the tissue composition of regenerated ‘dental pulp-like’ tissues，which collagen fibers are loosely and orderly arranged, and mineralized tissue is reduced, and macrophages aggregation can be seen. Based on the results of mRNA differential expression studies, we speculate that the PI3K / Akt pathway plays an important role in macrophage polarization. We hypothesis that the SDF-1 / PI3K / Akt signaling pathway can degrade excessively formed blood vessels, ECM, and reduce the formation of bone-like / mineralized tissues by regulating the polarization of macrophages. This study will explore the mechanism of SDF-1 / PI3K / Akt on macrophage recruitment and polarization through in vitro and in vivo experiments. And the effect of different subtypes of macrophages on ECM remodeling will be further verified. This study supposed to evaluate the role of SDF-1/PI3K /Akt in dental pulp tissue regeneration and provides a scientific basis for improving the histological composition of regenerative ‘dental pulp tissue’.