Research Paper Volume 13, Issue 16 pp 20651—20660
NLRC5 attenuates inflammatory response in IL-1β-stimulated human osteoarthritis chondrocytes through the NF-κB signaling pathway
- 1 Hand Surgery Department, Central Hospital Affiliated to Shen Yang Medical Collage, Shenyang 110024, Liaoning Province, China
Received: March 13, 2021 Accepted: August 14, 2021 Published: August 26, 2021https://doi.org/10.18632/aging.203453
How to Cite
Copyright: © 2021 Mu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
NOD-like receptor family caspase recruitment domain family domain containing 5 (NLRC5) has been found to be a critical mediator of inflammatory response. However, the role of NLRC5 in osteoarthritis (OA) has not been reported. Our results showed that NLRC5 was down-regulated by IL-1β induction in chondrocytes. Overexpression of NLRC5 in chondrocytes significantly suppressed IL-1β-induced inflammatory response through inhibiting the production of multiple inflammatory mediators including inducible nitric oxide synthases (iNOS), and cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), NO, TNF-α and IL-6, as well matrix metalloproteinase 3 (MMP-3) and MMP-13. Consistently, NLRC5 knockdown exhibited opposite effects on the production of these inflammatory mediators in IL-1β-induced chondrocytes. Furthermore, overexpression of NLRC5 increased the IĸBα expression, while decreased the p-p65 expression, indicating that NLRC5 inhibited the activation of NF-κB signaling. Additionally, inhibition of NF-κB by PDTC mitigated the si-NLRC5-mediated promotion of IL-1β-induced inflammatory injury in chondrocytes. Finally, NLRC5 treatment ameliorated cartilage degeneration in an OA model in rats. Taken together, these findings revealed that NLRC5 attenuated IL-1β-induced inflammatory injury in chondrocytes through regulating the NF-κB signaling.