Protective effects of Nebivolol against interleukin-1β (IL-1β)-induced type II collagen destruction mediated by matrix metalloproteinase-13 (MMP-13)

Zhigang Li, Baoyi Liu, Dewei Zhao, BenJie Wang, Yupeng Liu, Yao Zhang, Fengde Tian, Borui Li

The pathological progression of osteoarthritis (OA) involves degradation of articular cartilage matrix. Type II collagen is the main component of cartilage matrix, which is degraded by pro-inflammatory cytokines such as IL-1β mediated by MMP-13. Nebivolol, a licensed drug used for the treatment of hypertension in clinics, displays its anti-inflammatory capacity in various conditions. However, whether Nebivolol has a protective effect on cartilage matrix degradation has not been reported before. In this study, we investigated the effects of Nebivolol on regulating the expression of MMP-13 and degradation of type II collagen. Our results indicate that Nebivolol alleviated the increase in gene expression, protein expression, and activity of MMP-13 induced by IL-1β. Importantly, IL-1β strikingly reduced the levels of type II collagen in cell culture supernatants, which was reversed by treatment with Nebivolol in a dose-dependent manner. Mechanistically, Nebivolol was found to alleviate the increased levels of phosphorylated IκBα and reduced levels of total IκBα induced by IL-1β, which subsequently mitigated p65 nuclear translocation and the transcriptional activity of NF-κB. Furthermore, our results indicated that IL-1β treatment resulted in a significant increase in expression of the transcriptional factor interferon regulatory factor-1 (IRF-1) at both the mRNA and protein levels, which was significantly ameliorated by treatment with Nebivolol. The combination of these findings suggests that Nebivolol can potentially be applied in human OA treatment.