外泌体circNT5C3B调控Sufu促进脂肪干细胞成髓核分化的机制研究

椎间盘退行性疾病（DDD）是骨科常见的疾病，干细胞疗法是其中最有希望的疗法之一，但我们前期文章显示髓核分化不足限制了其修复效果。研究表明髓核外泌体能够促进干细胞髓核分化，但其具体机制不明。我们首次筛选到髓核外泌体中的circNT5C3B，发现其是髓核外泌体发挥作用的关键因素，并且和干细胞髓核分化SHH通路相关。同时预实验结果提示circNT5C3B与Sufu蛋白相结合。因此我们推测髓核细胞外泌体circNT5C3B通过Sufu调控脂肪干细胞成髓核分化。故本课题拟在体外开展研究髓核细胞外泌体circNT5C3B促进脂肪干细胞髓核分化的效应及靶分子机制，并在体内验证异种异体移植高表达circNT5C3B外泌体培养后的脂肪干细胞修复退变椎间盘的效果，为促进干细胞移植治疗DDD的临床应用提供有价值的理论指导和实验依据。

Intervertebral disc degenerative disease (DDD) is a common disease in orthopedics. Stem cell therapy is one of the most promising treatments, but our previous article showed that insufficient differentiation of the nucleus pulposus has limited its repair effect. Studies have shown that nucleus pulposus exosomes can promote stem cell differentiation, but the specific mechanism is unknown. We first screened circNT5C3B in nucleus pulposus exosomes and found that it is a key factor for nucleus pulposus exosomes to play a role, and we found that circNT5C3B is.related to the SHH pathway of stem cell nucleus differentiation. At the same time, pre-experimental results suggest that circNT5C3B may play a role through Sufu. Therefore, we speculate that nucleus pulposus exosomes circNT5C3B regulate the nucleus pulposus differentiation of adipose stem cells through Sufu. Therefore, this project intends to conduct a study in vitro on the effect of nucleus pulposus cell exosomes circNT5C3B on promoting the differentiation of adipose-derived stem cells and the target molecular mechanism, and to verify in vivo xenograft transplantation of circNT5C3B exosomes to repair degenerated intervertebral disc. The results will provide valuable theoretical guidance and experimental basis for promoting the clinical application of stem cell transplantation for DDD.