周围神经损伤修复一直是临床上的治疗难题，研究神经再生相关分子及其信号通路对于神经损伤后再生与功能恢复具有重要意义。有文献报道，SPP1在神经损伤后Wallerian溃变远端的雪旺细胞中表达上调且促进神经再生，但具体机制并不清楚。本课题组实验表明，SPP1能抑制细胞凋亡、促进细胞增殖；同时，SPP1上调PKCα、Bcl2和p-ERK的表达，因此推测SPP1通过促进雪旺细胞存活进而发挥促神经再生的作用；本项目拟在此基础上，通过使用PKCα siRNA、PKCα激动剂、CD44及αⅤβ3阻遏抗体等，证明SPP1通过CD44介导PKCα/Bcl2抑制细胞凋亡、PKCα/ERK促进细胞增殖；建立 SPP1-/- （或野生）小鼠坐骨神经损伤模型，同时给予PKCα激动剂（或PKCα siRNA），以揭示SPP1在体内通过PKCα促进损伤神经的再生和功能恢复的机制，为周围神经损伤治疗提供新思路。

The repair of injured peripheral nerve is always a challenge in clinic. Research on molecules and signaling pathways that contribute to nerve regeneration and functional recovery is extremely important. Recent studies showed that SPP1 was significantly up-regulated in distal Schwann cells during Wallerian degeneration, and the specific loss of SPP1 in Schwann cells impairs axon regeneration. However, the corresponding mechanism is still unknown. In our preliminary experiments, we found that SPP1 overexpression can inhibit cell apoptosis and promote cell proliferation. In addition, SPP1 increased the expression of PKCα and Bcl2 as well as phosphorylated ERK. Based on these observations, we hypothesize SPP1 promote Schwann cell viability to facilitate nerve regeneration. In detail, SPP1 could bind to CD44 receptor, which in turn inhibits apoptosis through PKCα/Bcl2 pathway and promotes proliferation through PKCα/ERK pathway in Schwann cells. In order to test this hypothesis, PKCα siRNA, PKCα agonist and CD44 or αⅤβ3 blocking antibodies will be used in primary cultured Schwann cells to test cell viability. Moreover, PKCα agonist (or PKCα siRNA) will be applied to sciatic nerve injury model of SPP1-/- transgenic (or wild type) mouse to further prove if SPP1 accelerates nerve regeneration and functional recovery in a PKCα dependent manner. Results from aforementioned proposal may provide new treatments for peripheral nerve regeneration.