Mitoregulin modulates inflammation in osteoarthritis: Insights from synovial transcriptomics and cellular studies

• Published in: Biochemical and biophysical research communications 2024-11, Vol.734, p.150652, Article 150652
• Main Authors: Choi, Minjeong, Min, Ju-Sik, Moon, Sang Won, Jeon, Jaewan, Do, Hwan-Kwon, Kim, Wanil
• Format: Article
• Language: English
• Subjects: Cell Line, Tumor; Cytokines; Humans; Inflammation; Inflammation - genetics; Inflammation - metabolism; Inflammation - pathology; Mitoregulin; Osteoarthritis; Osteoarthritis - genetics; Osteoarthritis - metabolism; Osteoarthritis - pathology; Synovial Membrane - metabolism; Synovial Membrane - pathology; Transcriptome
• ISSN: 0006-291X; 1090-2104; 1090-2104
• DOI: 10.1016/j.bbrc.2024.150652

Osteoarthritis is a prevalent musculoskeletal disease that involves cartilage degradation, subchondral bone remodeling, and synovial inflammation and ultimately causes physical disability. Common risk factors for osteoarthritis include age, sex, obesity, and genetic predispositions. Treatment includes nonpharmaceutical and pharmacological approaches; however, disease-modifying osteoarthritis drugs remain undeveloped. We aimed to identify key regulatory factors underlying the etiology of osteoarthritis. We studied alterations of the inflammatory responses after manipulating the expression of MTLN, which we selected after sequencing and transcriptomics of the patients’ synovial tissues. MTLN expression was increased in synovial tissues of patients and in SW982 human synovial sarcoma cells following inflammatory stimuli. We found that MTLN overexpression or knockout respectively decreased or increased expression of the inflammation-associated genes, including IL-6, IL-8, and TNF-α. Thus, high levels of MTLN in osteoarthritis may protect tissues against excessive inflammation, thereby offering therapeutic potentials. •We identified mitoregulin (MTLN) as a regulatory factor affecting OA progression.•MTLN expression high in synovial tissues of OA patients after inflammatory stimuli.•MTLN overexpression downregulated inflammatory factors (IL-6, IL-8, and TNF-α).•Thus, MTLN may serve as a biomarker and therapeutic target for OA treatment.