Background: N6-methyladenosine (m6A) methylation modification is involved in the regulation of various biological processes, including inflammation, antitumor, and antiviral immunity. However, the role of m6A modification in the pathogenesis of autoimmune diseases has been rarely reported. Methods: Based on a description of m6A modification and the corresponding research methods, this review systematically summarizes current insights into the mechanism of m6A methylation modification in autoimmune diseases, especially its contribution to rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Results: By regulating different biological processes, m6A methylation is involved in the pathogenesis of autoimmune diseases and provides a promising biomarker for the diagnosis and treatment of such diseases. Notably, m6A methylation modification is involved in regulating a variety of immune cells and mitochondrial energy metabolism. In addition, m6A methylation modification plays a role in the pathological processes of RA, and m6A methylation-related genes can be used as potential targets in RA therapy. Conclusions: M6A methylation modification plays an important role in autoimmune pathological processes such as RA and SLE and represents a promising new target for clinical diagnosis and treatment, providing new ideas for the treatment of autoimmune diseases by targeting m6A modification-related pathways.

Objective: Knee Osteoarthritis (KOA), is the most common joint disease worldwide. The pathogenesis of KOA is complex and electroacupuncture (EA) is an effective therapy for KOA, but the mechanism remains unclear. In this study, we aim to investigate the potential therapeutic effect of EA on the rat model of KOA induced by monosodium iodoacetate (MIA) and its relationship with NLRP3 inflammasome by immunohistochemistry and western blot. Methods: KOA was induced by intra-articular injection of MIA (3 mg/50 μL) into the right knee joint of rats. Forty-five male rats weighing 250–300 g were randomly divided into 3 groups: control group, KOA group, and KOA + electroacupuncture group (KOA+EA). EA treatment lasted for 2 weeks (6 times a week). Paw withdrawal threshold tests were used to assess mechanical allodynia once a week. Safranin O/Fast Green and hematoxylin and eosin (H&E) staining were used to assess the damage to cartilage, synovium, and subpatellar fat pad (IFP). Immunohistochemistry was used to observe NLRP3 inflammasome-associated protein-positive cells in the same field of view and western blot was used to detect the expression of the associated protein in cartilage tissue. Results: The KOA group showed mechanical hyperalgesia, joint inflammation, and significant cartilage tissue destruction. Safranin O/Fast Green and H&E staining revealed that EA alleviated the joint pathological changes caused by KOA and had a protective effect on cartilage, synovium, and IFP destruction. Mechanical allodynia pain and joint swelling were reduced in KOA rats after EA treatment. Immunohistochemistry and western blot showed significant inhibition of NLRP3 inflammasome-associated protein. Conclusion: The results indicate that EA can inhibit NLRP3 inflammasome and reduce pyroptosis, which results in the protection of cartilage tissue and the treatment of KOA. It provides reliable evidence for the development of EA in the treatment of KOA and the clinical application of acupuncture.

The aim of this study is to investigate the role of Sirtuin1 (Sirt1) in the regulation of autophagy for human osteoarthritis (OA) chondrocytes. All cartilage samples were collected from human donors, including young group, aged group, and OA group. Primary chondrocytes were isolated and cultured with Sirt1 activator or inhibitor. Sirt1 expression in cartilage tissue and chondrocytes was evaluated, and the deacetylation activity of Sirt1 was determined. The alteration of autophagy activity after upregulating or downregulating Sirt1 was detected. Chondrocytes were treated with autophagy activator and inhibitor, and then the protein level of Sirt1 was examined. The interactions between Sirt1 and autophagy-related proteins Atg7, microtubule associated protein 1 light chain 3 (LC3), and Beclin-1 were determined by using immunoprecipitation. The assay of articular cartilage revealed that the expression of Sirt1 might be age-related: highly expressed in of younger people, and respectively decreased in the elderly people and OA patients. In vitro study was also validated this result. Further study confirmed that higher levels of Sirt1 significantly increased autophagy in aged chondrocytes, while the lower expression of Sirt1 reduced autophagy in young chondrocytes. Of note, the high levels of Sirt1 reduced autophagy in OA chondrocytes. When the chondrocytes were treated with autophagy activator or inhibitor, we found the expression of Sirt1 was not affected. In addition, we found that Sirt1 could interact with Atg7. These results suggest that Sirt1 in human chondrocytes regulates autophagy by interacting with autophagy related Atg7, and Sirt1 may become a more important target in OA treatment.