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脐带血间充质干细胞通过微小RNA-29a-3p/FOS轴分泌的长链非编码RNA H19在晚期骨关节炎疼痛中枢敏化中的作用

LncRNA H19 secreted by umbilical cord blood mesenchymal stem cells through microRNA-29a-3p/FOS axis for central sensitization of pain in advanced osteoarthritis.

作者信息

Yang Qinyan, Yao Yutong, Zhao Daqiang, Zou Haibo, Lai Chunyou, Xiang Guangming, Wang Guan, Luo Le, Shi Ying, Li Yan, Yang Maozhu, Huang Xiaolun

机构信息

Department of Hepatobiliary and Pancreatic Surgery, Cell Transplantation Center, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital Chengdu 610072, China.

Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital Chengdu 610072, China.

出版信息

Am J Transl Res. 2021 Mar 15;13(3):1245-1256. eCollection 2021.

Abstract

OBJECTIVE

To explore the molecular mechanism of umbilical cord blood mesenchymal stem cells (UCBMSCs) in the treatment of advanced osteoarthritis pain.

METHODS

Normal healthy rats were selected to establish advanced osteoarthritis (OA) model, and the rats were randomly divided into control group, intravenous group, intracavitary group and intrathecal group. The intravenous group received intravenous injection of UCBMSCs, intracavitary group received intra-articular injection of UCBMSCs, and intrathecal group received subarachnoid injection of UCBMSCs. The pain behavior and serum pro-inflammatory factor levels were evaluated before and after treatment. microRNA-29a-3p and FOS mRNA in spinal dorsal horn was detected using qPCR, the phosphorylation of c-fos protein and NR1, NR2B, ERK and PKCg was detected using Western blot, and the level of LncRNA H19 was detected using qPCR.

RESULTS

LncRNA H19 was enriched in the exosomes of UCBMSCs. microRNA-29a-3p was the target gene of LncRNA H19, while FOS was the downstream target of microRNA-29a-3p. Pain and inflammation of rats in the intrathecal group improved best, and the phosphorylation levels of c-fos and NR1, NR2B, ERK and PKCg in the spinal dorsal horn of the intrathecal group decreased. LncRNA H19 regulated the central sensitization of astrocytes through microRNA-29a-3p/FOS axis.

CONCLUSION

Intrathecal injection of umbilical cord blood mesenchymal stem cells can improve the pain and central sensitization of advanced osteoarthritis through LncRNA H19/microRNA-29a-3p/FOS axis.

摘要

目的

探讨脐带血间充质干细胞(UCBMSCs)治疗晚期骨关节炎疼痛的分子机制。

方法

选取正常健康大鼠建立晚期骨关节炎(OA)模型,将大鼠随机分为对照组、静脉注射组、腔内注射组和鞘内注射组。静脉注射组静脉注射UCBMSCs,腔内注射组关节腔内注射UCBMSCs,鞘内注射组蛛网膜下腔注射UCBMSCs。治疗前后评估疼痛行为和血清促炎因子水平。采用qPCR检测脊髓背角中microRNA-29a-3p和FOS mRNA,采用蛋白质免疫印迹法检测c-fos蛋白及NR1、NR2B、ERK和PKCg的磷酸化水平,采用qPCR检测LncRNA H19水平。

结果

LncRNA H19在UCBMSCs的外泌体中富集。microRNA-29a-3p是LncRNA H19的靶基因,而FOS是microRNA-29a-3p的下游靶标。鞘内注射组大鼠的疼痛和炎症改善最佳,鞘内注射组脊髓背角中c-fos及NR1、NR2B、ERK和PKCg的磷酸化水平降低。LncRNA H19通过microRNA-29a-3p/FOS轴调节星形胶质细胞的中枢敏化。

结论

鞘内注射脐带血间充质干细胞可通过LncRNA H19/microRNA-29a-3p/FOS轴改善晚期骨关节炎的疼痛和中枢敏化。

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