Methylation Regulation of LPCAT3 Improves Osteoarthritis by Regulating ACSL4 to Inhibit Chondrocyte Ferroptosis

Author:

Habaxi Kaken,Wang Wei,Taximaimaiti Maimaitiaili,Wang Li

Abstract

With the increasing aging population in China, the incidence rate of knee osteoarthritis is expected to rise annually. Therefore, we conducted a study to investigate the crucial role of LPCAT3 in osteoarthritis and its underlying mechanisms. We collected samples from normal volunteers (<i>n</i> &#61; 12) and patients with osteoarthritis (<i>n</i> &#61; 12) at our hospital. It was observed that LPCAT3 mRNA expression was reduced and positively correlated with IL-1&beta; mRNA expression in patients with osteoarthritis. In a mouse model, LPCAT3 mRNA and protein expression were found to be suppressed. Furthermore, in an <i>in vitro</i> model, the enrichment level of LPCAT3 mRNA was inhibited by a specific m6A antibody through si-METTL3. Si-METTL3 also reduced the stability of LPCAT3 mRNA in the <i>in vitro</i> model. The inhibition of LPCAT3 was found to exacerbate osteoarthritis in the mouse model. Additionally, LPCAT3 was shown to reduce inflammation in the<i> in vitro</i> model. It was also observed that LPCAT3 reduced chondrocyte ferroptosis by inhibiting mitochondrial damage. LPCAT3 protein was found to interact with ACSL4 protein, and its up-regulation suppressed ACSL4 expression in the <i>in vitro</i> model. ACSL4 was identified as a target of LPCAT3 for suppressing mitochondrial damage in the <i>in vitro </i>model. In conclusion, this study demonstrates that LPCAT3 improves osteoarthritis by regulating ACSL4 to inhibit chondrocyte ferroptosis, thus providing a novel target for the treatment of osteoarthritis.

Publisher

Begell House

Subject

Genetics,Molecular Biology

Reference35 articles.

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