Monotropein accelerates chondrocyte progression in osteoarthritis by alleviating TNF-α induced inflammation through regulation of MAPK/NF-κB signaling pathway

Background: Osteoarthritis (OA) is a common degenerative musculoskeletal disease in elderly people over 50 years old. Inflammatory response of chondrocytes in OA during treatment vitiated the treatment outcomes. Antiinflammatory ingredient monotropein has been used in the treatment of OA. However, the molecular mechanism of monotropein in inflammatory response of chondrocytes is unclear. Methods: Cell viability of primary chondrocytes and ATDC5 cells was determined by CCK8 assay. Cell apoptosis was examined by flow cytometry assay. The production of nitric oxide (NO) was detected using Griess reagent. The release of inflammatory cytokines interleukin-1 (IL-1), interleukin-6 (IL-6) and interleukin-12 (IL-12) was measured by enzyme linked immunosorbent assay (EUSA). The expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) was assessed by qRT-PCR. Protein expression of iNOS, COX-2, matrix metalloproteinases (MMP-1, MMP-3, MMP-13), p-p65, p65, IkapaB kinase proteins (p-IKK-alpha/beta, IKK-alpha, IKK-beta), inducible nuclear I kappa B proteins (p-I kappa B-alpha, I kappa B-alpha), p-ERK1/2, ERK1/2, p-p38 and p38 was analysed by western blot assay. Results: Monotropein exhibited negligible influences on chondrocyte survival. In addition, monotropein alleviated tumor necrosis factor-alpha (TNF-alpha) induced inhibition on viability and promotion on apoptosis in chondrocytes. The production of NO, inflammatory cytokines IL-1, IL-6 and IL-12 was enhanced by TNF-alpha and suppressed gradually by monotropein. Moreover, monotropein attenuated TNF-alpha induced release of iNOS, COX-2 MMP-1, MMP-3 and MMP-13 in chondrocytes. Besides, monotropein blocked TNF-alpha induced mitogen-activated protein kinase (MAPK)/NF-kappa B activation in chondrocytes. Conclusion: Monotropein accelerates chondrocyte progression of in OA by alleviating TNF-alpha induced inflammation through regulation of MAPK/NF-kappa B signaling pathway, providing novel therapy strategy for OA.