SNIP1 reduces extracellular matrix degradation and inflammation via inhibiting the NF-κB signaling pathway in osteoarthritis

Abstract

Osteoarthritis (OA), the most common joint disease, is characterized by inflammation and cartilage degradation. Previous studies illustrated that Smad nuclear-interacting protein 1 (SNIP1) is an inhibitor of the TGF-β signal transduction pathway and SNIP1 has been reported as an anti-inflammatory factor. This study aimed to explore the role of SNIP1 in OA progression. In this study, the SNIP1 expression was evaluated in OA human and OA mice tissue and interleukin-1 beta (IL-1β)-induced chondrocytes. The Safranin-O (SO) staining and osteoarthritis research society international (OARSI) scoring system was used to evaluate cartilage injury. The gain- and loss-of-function studies for SNIP1 were performed in chondrocytes. The SNIP1 overexpression adenovirus was injected into mice by intra-articular injection. The SNIP1 expression was decreased in OA patients, OA mice, and IL-1β-stimulated chondrocytes. The cartilage injury of medial meniscus-induced OA (DMM-OA) mice at 8 weeks showed more severe than that at 4 weeks. The expression of SNIP1 was lower at 8 weeks than that at 4 weeks. In IL-1β-stimulated chondrocytes, SNIP1 overexpression reduced the expression of TNF-α and IL-6, alleviated ECM degradation, reduced the phosphorylation levels of p65 and IκBα, and decreased the p65 level in nuclear. Moreover, overexpression of SNIP1 alleviated cartilage injury in DMM-OA mice. In brief, our study suggested that SNIP1 alleviated OA and repressed inflammation by inhibiting the activation of NF-κB. This study might provide a new insight into OA treatment.

Keywords: Chondrocytes; Extracellular matrix; Inflammation; NF-κB; Osteoarthritis; SNIP1.