Silencing SGK1 alleviates osteoarthritis through epigenetic regulation of CREB1 and ABCA1 expression

Aim: Osteoarthritis (OA) is the most common joint disorder and a leading cause of disability. While early proactive management is crucial in alleviating symptoms in OA patients, currently available therapeutic approaches are yet to achieve an ideal level of efficacy. The path to the development of a potent treatment begins with the thorough understanding of the pathophysiology of OA. The present study aims to explore the mechanism by which SGK1 is involved in OA progression. Methods: Firstly, the potential target gene of SGK1 was screened and SGK1 expression was determined in OA through bioinformatics analysis. Mouse OA model was then established and chondrocytes were extracted, after which inflammation was induced with lipopolysaccharide (LPS). Following LPS treatment, the chondrocytes were transfected with synthesized plasmids to explore the impact of SGK1, CREB1, and ABCA1 on apoptosis, proliferation and inflammation in OA. ChIP-PCR and dual-luciferase reporter gene assay were conducted to determine the binding relation between SGK1 and CREB1 as well as between CREB1 and ABCA1. Results: OA mice presented with high expression of SGK1. Interestingly, we found that SGK1 inhibited CREB1 expression in chondrocytes, thereby inducing inflammation and suppressing chondrocyte proliferation. CREB1 was found to have a positive correlation with ABCA1 expression, while down-regulation of CREB1 resulted in the inhibition of cell proliferation and aggravated inflammation, which could be reversed by overexpressed ABCA1. Conclusion: Taken altogether, silencing of SGK1 alleviated OA through epigenetic regulation of CREB1 and ABCA1 expression. These findings may provide novel insight into SGK1-based strategy for OA treatment.

Automated summary

This study elucidates the mechanism by which SGK1 is involved in the progression of osteoarthritis, showing that it inhibits CREB1 expression in chondrocytes, leading to inflammation and suppression of chondrocyte proliferation. CREB1 is positively correlated with ABCA1 expression, and down-regulation of CREB1 inhibits cell proliferation and exacerbates inflammation, which can be reversed by overexpression of ABCA1.