ABSTRACT
OBJECTIVE: Inflammation plays a crucial part in osteoarthritis (OA) development. This work aimed to explore loganin's role and molecular mechanism in inflammation and clarify its anti-inflammatory effects in OA treatment. METHODS: Chondrocytes were stimulated using interleukin (IL)-1ß and loganin at two concentrations (1 µM and 10 µM). Nitric oxide (NO) and prostaglandin E2 (PGE2) expression was assessed. Real-time polymerase chain reaction was used to evaluate inducible NO synthase (iNOS), cyclooxygenase (COX)-2, IL-6, and tumor necrosis factor (TNF)-α mRNA levels. Western blot was used to investigate TLR4, MyD88, p-p65, and IκB-α expression. p65 nuclear translocation, synovial inflammatory response, and cartilage degeneration were also assessed. RESULTS: Loganin significantly reduced IL-1ß-mediated PGE2, NO, iNOS, and COX-2 expression compared with that of the IL-1ß stimulation group. The TLR4/MyD88/NF-κB pathway was suppressed by loganin, which decreased inflammatory cytokine (TNF-α and IL-6) levels compared with those of the IL-1ß stimulation group. Loganin inhibited IL-1ß-mediated NF-κB p65 nuclear translocation compared with that of the IL-1ß stimulation group. Loganin partially suppressed cartilage degeneration and the synovial inflammatory response in vivo. CONCLUSION: This work demonstrated that loganin inhibited IL-1ß-mediated inflammation in rat chondrocytes through TLR4/MyD88/NF-κB pathway regulation, thereby reducing rat cartilage degeneration and the synovial inflammatory response.
Subject(s)
NF-kappa B , Osteoarthritis , Animals , Cartilage/pathology , Chondrocytes/metabolism , Cyclooxygenase 2/genetics , Cyclooxygenase 2/metabolism , Cyclooxygenase 2/pharmacology , Dinoprostone , Inflammation/pathology , Interleukin-1beta/genetics , Interleukin-1beta/metabolism , Interleukin-6/genetics , Interleukin-6/metabolism , Iridoids , Myeloid Differentiation Factor 88/genetics , Myeloid Differentiation Factor 88/metabolism , Myeloid Differentiation Factor 88/pharmacology , NF-kappa B/metabolism , Nitric Oxide/metabolism , Osteoarthritis/pathology , Rats , Signal Transduction , Toll-Like Receptor 4/genetics , Toll-Like Receptor 4/metabolism , Tumor Necrosis Factor-alpha/metabolismABSTRACT
Lumbar spinal stenosis is a common orthopedic disease in clinical practice at present. Postoperative cognitive dysfunction (POCD) refers to the phenomenon of impaired memory. However, whether long noncoding RNA (LncRNA) GAS5 contributes to the mechanism of cognitive function in undergoing lumbar spinal canal decompression remains unknown. Thus, the present study investigated the precise details of LncRNA GAS5 involvement in Postoperative cognitive dysfunction of patients undergoing lumbar spinal canal decompression. Patients undergoing lumbar spinal canal decompression with cognitive function and Normal healthy volunteers were obtained. C57BL/6 mice were maintained with a 2% concentration of sevoflurane in 100% oxygen at a flow rate of 2 L minute-1 for 4 hours. LncRNA GAS5 gene expression were up-regulated in patients undergoing lumbar spinal canal decompression. In mice model, LncRNA GAS5 gene expression also increased. LncRNA GAS5 promoted neuroinflammation in vitro model. LncRNA GAS5 raised cognitive impairment and increased neuroinflammation in mice model. LncRNA GAS5 suppressed miR-137 in vitro model. MiR-137 reduced neuroinflammation in vitro model. MiR-137 suppressed TCF4 protein expression in vitro model. Transcription factor TCF4 activates the expression of bHLH. Taking together, this experiment provide the first experimental and clinical evidence that LncRNA GAS5/miR-137 promoted anesthesia-induced cognitive function to increase inflammatory bodies in patients undergoing lumbar spinal canal decompression, suggesting it may be a biomarker of POCD and a potential therapeutic target for POCD.
