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

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.