Qinyan Yang1,2, Yutong Yao1,2, Daqiang Zhao3, Haibo Zou1,2, Chunyou Lai1,2, Guangming Xiang1,2, Guan Wang1,2, Le Luo1,2, Ying Shi4, Yan Li4, Maozhu Yang1,2, Xiaolun Huang1,2. 1. Department of Hepatobiliary and Pancreatic Surgery, Cell Transplantation Center, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital Chengdu 610072, China. 2. Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital Chengdu 610072, China. 3. Department of Anesthesiology, Shanghai Jiahui International Hospital Shanghai 200233, China. 4. School of Medicine, University of Electronic Science and Technology of China Chengdu 610054, Sichuan, China.
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. AJTR
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. AJTR