Oxidative stress mediated decrement of spinal endomorphin-2 contributes to lumbar disc herniation sciatica in rats.

Increasing evidence supported that oxidative stress induced by herniated lumbar disc played important role in the formation of lumbar disc herniation sciatica (LDHS), however, the neural mechanisms underlying LDHS need further clarification. Endomorphin-2 (EM2) is the endogenous ligand for mu-opioid receptor (MOR), and there is increasing evidence implicating the involvement of spinal EM2 in neuropathic pain. In this study, using an nucleus pulposus implantation induced LDHS rat model that displayed obvious mechanical allodynia, it was found that the expression of EM2 in dorsal root ganglion (DRG) and spinal cord was significantly decreased. It was further found that oxidative stress in DRG and spinal cord was significantly increased in LDHS rats, and the reduction of EM2 in DRG and spinal cord was determined by oxidative stress dominated increment of dipeptidylpeptidase IV activity. A systemic treatment with antioxidant could prevent the forming of mechanical allodynia in LDHS rats. In addition, MOR expression in DRG and spinal cord remained unchanged in LDHS rats. Intrathecal injection of MOR antagonist promoted pain behavior in LDHS rats, and the analgesic effect of intrathecal injection of EM2 was stronger than that of endomorphin-1 and morphine. Taken together, our findings suggest that oxidative stress mediated decrement of EM2 in DRG and spinal cord causes the loss of endogenous analgesic effects and enhances the pain sensation of LDHS.

MicroRNA-101a-3p could be involved in the pathogenesis of temporomandibular joint osteoarthritis by mediating UBE2D1 and FZD4.

BACKGROUND: Temporomandibular joint osteoarthritis (TMJOA) is a degenerative disease that gradually affects the articular cartilage, synovium, and bone structure. To date, the molecular mechanism of TMJOA pathogenesis remains unclear. The aim of this study was to explore the biological function of the micro-ribonucleic acid 101a-3p (miR-101a-3p) and its role in TMJOA. METHODS: We detected the effect of interleukin-1ß (IL-1ß) on chondrocyte proliferation using Cell Counting Kit-8 (CCK-8) technology. Using quantitative polymerase chain reaction (qPCR), we detected transcription levels of miR-101a-3p in a rat model with TMJOA and inflamed chondrocytes, as well as in a group of normal rats. The effect of miR-101a-3p on apoptosis was examined in vitro using flow cytometry (FCM). We then analyzed the target of miR-101a-3p via bioinformatics and confirmed it using a luciferase reporter assay (LRA). RESULTS: We showed that IL-1ß could inhibit proliferation of chondrocytes. We found that miR-101a-3p levels were significantly lower in the rat inflammation model with TMJOA and inflamed chondrocytes than in the normal group. Additionally, miR-101a-3p substantially promoted apoptosis of chondrocytes, and both bioinformatic analyses and LRA found that this miRNA targeted the genes ubiquitin-conjugating enzyme 2D1 (UBE2D1) and Frizzled class receptor 4 (FZD4). CONCLUSION: Our results suggested that miR-101a-3p was involved in the pathogenesis of TMJOA and that its mechanism was probably interaction with its target genes UBE2D1 and FZD4.