Abstract
Long non-coding RNA (LncRNA) small nucleolar RNA host gene 1 (SNHG1) has been reported in the occurrence and development of several diseases, but its biological role and mechanism in osteoarthritis (OA) remain to be illuminated. In the present research, we aimed to investigate the effect of SNHG1 on IL-1β-induced OA and its molecular mechanism. Results revealed that SNHG1 decreased the expression of MMPs, ADAMTs, collagen, and aggrecan, and ameliorates IL-1β-induced metabolic dysfunction in normal human chondrocytes-keen. In addition, SNHG1 inhibited the expressions of pro-inflammatory cytokines in chondrocytes, including NO, PGE2, IL-6, TNF-α, i-NOS, and COX-2. Furthermore, luciferase reporter assay demonstrated that SNHG1 could directly interact with miR-16-5p and suppressed miR-16-5p expression and activity. What is more, miR-16-5p overexpression reversed SNHG1-inhibited aberrant catabolism and inflammation triggered by IL-1β stimulation. Finally, SNHG1 inhibits the expression of miR-16-5p-mediated factors involved in p38MAPK and NF-κB signaling pathways, including ERK1/2, p-p38 and p-p65. Taken together, the results of our studies illuminate that SNHG1 alleviates the inflammation of IL-1β-induced OA through the activation of miR-16-5p-mediated p38MAPK and NF-κB signaling pathway. It suggested that SNHG1 may serve as a potential target for OA diagnosis and treatment.
Highlights
Osteoarthritis (OA) is a joint disease characterized by abnormal apoptosis of articular chondrocyte, cartilage sclerosis, and inflammation [1]
Normal human chondrocytes-keen were transfected with empty plasmid pcDNA3.0 or overexpression plasmid lnc-small nucleolar RNA host gene 1 (SNHG1), respectively and treated with IL-1β (10 ng/ml) for 24 h
Results exhibited that the SNHG1 expression was decreased after treatment with IL-1β, and SNHG1 was most highly expressed in lnc-SNHG1 group compared with pcDNA3 group, while there was no significant difference in the expression of SNHG1 in control group and pcDNA3 group (Figure 1A)
Summary
Osteoarthritis (OA) is a joint disease characterized by abnormal apoptosis of articular chondrocyte, cartilage sclerosis, and inflammation [1]. It is reported that many factors play a key role in the pathogenesis of OA such as IL-6, TNF-α, and IL-1β, and several inflammatory signaling pathways are involved in the regulation of OA [3]. NF-κB and p38MAPK, as critical inflammatory signaling pathways, play an important role in the development of OA. Studies have found that NF-κB and p38MAPK signaling pathway are activated in the articular cartilage and synovial cells of occurrence of OA [4]. The high expression of p-p38 may promote the expression of NF-κB, which plays an important role in the occurrence and development of OA [5]. Recent studies have reported the key role of NF-κB in joint health, which regulates the response to joint injury and inflammation by regulating cytokines, such as IL-1β, TNF-α [6]. It is well known that phosphorylation of p65 is essential in the NF-κB pathway, and Rap, a critical protein, participates in the regulation of the NF-κB pathway by regulating the phosphorylation of p65 under physiological conditions
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