Icariin alleviates osteoarthritis by inhibiting NLRP3-mediated pyroptosis

Yan Zu,Yue Mu,Hong-Juan Yan,Shu-Ting Zhang,Qiang Li

doi:10.1186/s13018-019-1307-6

Abstract

BackgroundOsteoarthritis (OA) is the common chronic degenerative joint bone disease that is mainly featured by joint stiffness and cartilage degradation. Icariin (ICA), an extract from Epimedium, has been preliminarily proven to show anti-osteoporotic and anti-inflammatory effects in OA. However, the underlying mechanisms of ICA on chondrocytes need to be elucidated.MethodsLPS-treated chondrocytes and monosodium iodoacetate (MIA)-treated Wistar rats were used as models of OA in vitro and in vivo, respectively. LDH and MTT assays were performed to detect cytotoxicity and cell viability. The expression levels of NLRP3, IL-1β, IL-18, MMP-1, MMP-13, and collagen II were detected by qRT-PCR and Western blotting. The release levels of IL-1β and IL-18 were detected by ELISA assay. Caspase-1 activity was assessed by flow cytometry. Immunofluorescence and immunohistochemistry were used to examine the level of NLRP3 in chondrocytes and rat cartilage, respectively. The progression of OA was monitored with hematoxylin-eosin (H&E) staining and safranin O/fast green staining.ResultsICA could suppress LPS-induced inflammation and reduction of collagen formation in chondrocytes. Furthermore, ICA could inhibit NLRP3 inflammasome-mediated caspase-1 signaling pathway to alleviate pyroptosis induced by LPS. Overexpression of NLRP3 reversed the above changes caused by ICA. It was further confirmed in the rat OA model that ICA alleviated OA by inhibiting NLRP3-mediated pyroptosis.ConclusionICA inhibited OA via repressing NLRP3/caspase-1 signaling-mediated pyroptosis in models of OA in vitro and in vivo, suggesting that ICA might be a promising compound in the treatment of OA.

Highlights

Osteoarthritis (OA) is a long-term joint bone disorder which is recognized by the progressive damage of joint structure, such as articular cartilage and subchondral bone [1]
LPS induces inflammation and reduction of collagen formation in chondrocytes The expressions of NRLP3, IL-1β, and IL-18 in chondrocytes were examined by quantitative real time-PCR (qRT-PCR) following treatment of LPS
The expression levels of MMP-1, MMP-13, collagen II, NRLP3, IL-1β, and IL-18 in LPS-treated rat chondrocytes were monitored by Western blotting (Fig. 1c, d)

Summary

Introduction

Osteoarthritis (OA) is a long-term joint bone disorder which is recognized by the progressive damage of joint structure, such as articular cartilage and subchondral bone [1]. The treatment agents have failed to block the progression of OA, safer and better-tolerated drugs for OA therapy are needed [2]. Pyroptosis is a caspase-1-required inflammasomemediated programmed cell death signal pathway. Distinct from apoptosis and simple cell necrosis, the process of pyroptosis is proinflammatory and mediated by nod-like receptor protein-3 (NLRP3) inflammasome and caspase-1 signaling. A recent study demonstrated that NLRP inflammasomes NLRP1 and NLRP3 participated in the mediation of. Osteoarthritis (OA) is the common chronic degenerative joint bone disease that is mainly featured by joint stiffness and cartilage degradation. The underlying mechanisms of ICA on chondrocytes need to be elucidated

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Discussion

Conclusion