We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Protective effects of Nebivolol against interleukin-1β (IL-1β)-induced type II collagen destruction mediated by matrix metalloproteinase-13 (MMP-13).
- Authors
Li, Zhigang; Liu, Baoyi; Zhao, Dewei; Wang, BenJie; Liu, Yupeng; Zhang, Yao; Tian, Fengde; Li, Borui
- Abstract
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.
- Subjects
OSTEOARTHRITIS; NEBIVOLOL hydrochloride; INTERLEUKIN-1; MATRIX metalloproteinases; PROTEIN expression; GENE expression profiling
- Publication
Cell Stress & Chaperones, 2017, Vol 22, Issue 6, p767
- ISSN
1355-8145
- Publication type
Article
- DOI
10.1007/s12192-017-0805-x