脊髓损伤后由少突胶质细胞（OL）变性死亡引发的白质病变是影响功能恢复的关键原因之一，OL前体细胞(OPC)移植被认为是治疗新希望，但损伤微环境内存在不利于移植细胞存活和形成髓鞘的因素。研究显示，损伤后显著上调的BMP是影响OL分化成熟的关键分子。我们的前期研究表明，增强和阻断BMP信号均会抑制OL成熟和髓鞘形成，提示BMP信号下游存在功能不同的靶基因，可能对髓鞘形成和损伤修复发挥不同作用。新近研究发现，核转录因子Sip1可通过作用于下游靶基因，逆转BMP信号激活对OL形成的抑制作用。因此，本项目拟用Sip1干预OPC上的BMP信号，观察Sip1基因过表达或缺失对OPC细胞生物学活性及其内BMP信号活性的影响；并进一步在脊髓损伤模型上研究Sip1基因修饰的OPC移植后形成髓鞘和修复损伤的能力。研究结果将揭示BMP信号对OL形成和脊髓损伤修复的作用，为OPC移植治疗脊髓损伤开拓新思路。

The demyelination of white matter is one of critical factors to suppress the functional restoration after spinal cord injury.Transplantation of oligodendrocytes precursor cells(OPC) is becoming more highlighted for their advantaged ability to generate myelinating oligodendrocytes. While there exists some factors to inhibit the survival and myelinogenesis of transplanted OPC in the microenvironment of lesion. A lot of reports has demonstrated that the bone morphogenetic proteins (BMP) upregulated dramaticly post-injury were play the key roles on the myelination,our preliminary study indicated that both enhancing and blocking the BMP signaling inhibited the maturation and myelinogenesis of oligodendrocytes, it remind the downstream of the BMP signaling exsits the different target genes which play different functions on oligodendrocyte maturation and injury recovery.The recent reports showed that the smad interacting protein-1 (Sip1) could antagonize BMP signaling to promote the myelination through acting as a transcriptional repressor of Smad activity, and promoting activation of Olig1/Olig2 transcriptional activity.Therefore, the present project is designed to explore the effects of interfering BMP signaling via Sip1 gene modification on the activity of signal and ability to remyelination and rehabitation of injury spinal cord. The expected results will hopeful uncover the overall roles of BMP signaling on the genesis of oligodendrocyte and recovery of spinal cord injury, and then provide new therapeutic methods for OPC transplantation to remedy spinal cord injury.