IRF1 governs the expression of SMARCC1 via the GCN5-SETD2 axis and actively engages in the advancement of osteoarthritis

作者：Dong Wang, Yujun Zhang, Liangping Zhang, Du He, Lan Zhao, Zhimin Miao, Wei Cheng, Chengyue Zhu, Li Zhu, Wei Zhang, Hongting Jin, Hang Zhu, Hao Pan · 发表于：Journal of Orthopaedic Translation · 年份：2024 · DOI：10.1016/j.jot.2024.01.002 · 被引用次数：6 · 研究领域：Chromatin Remodeling and Cancer、Osteoarthritis Treatment and Mechanisms、RNA regulation and disease

Background: Osteoarthritis (OA) is a degenerative joint disease characterized by the breakdown of joint cartilage and underlying bone. Macrophages are a type of white blood cell that plays a critical role in the immune system and can be found in various tissues, including joints. Research on the relationship between OA and macrophages is essential to understand the mechanisms underlying the development and progression of OA. Objective: This study was performed to analyze the functions of the IRF1-GCN5-SETD2-SMARCC1 axis in osteoarthritis (OA) development. Methods: A single-cell RNA sequencing (scRNA-seq) dataset, was subjected to a comprehensive analysis aiming to identify potential regulators implicated in the progression of osteoarthritis (OA). In order to investigate the role of IRF1 and SMARCC1, knockdown experiments were conducted in both OA-induced rats and interleukin (IL)-1β-stimulated chondrocytes, followed by the assessment of OA-like symptoms, secretion of inflammatory cytokines, and polarization of macrophages. Furthermore, the study delved into the identification of aberrant epigenetic modifications and functional enzymes responsible for the regulation of SMARCC1 by IRF1. To evaluate the clinical significance of the factors under scrutiny, a cohort comprising 13 patients diagnosed with OA and 7 fracture patients without OA was included in the analysis. Results: IRF1 was found to exert regulatory control over the expression of SMARCC1, thus playing a significant r...