Melatonin Regulates Rheumatoid Synovial Fibroblasts-Related Inflammation: Implications for Pathological Skeletal Muscle Treatment

IF 8.3 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Journal of Pineal Research Pub Date : 2024-09-24 DOI:10.1111/jpi.13009
Chen-Ming Su, Chun-Hao Tsai, Hsien-Te Chen, Yi-Syuan Wu, Shun-Fa Yang, Chih-Hsin Tang
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Abstract

Melatonin has been reported to regulate circadian rhythms and have anti-inflammatory characteristics in various inflammatory autoimmune diseases, but its effects in diseases-associated muscle atrophy remain controversial. This study is aimed to determine the evidence of melatonin in rheumatoid arthritis (RA)-related pathological muscle atrophy. We used initially bioinformatics results to show that melatonin regulated significantly the correlation between pro-inflammation and myogenesis in RA synovial fibroblasts (RASF) and myoblasts. The conditioned medium (CM) from melatonin-treated RASF was incubated in myoblasts with growth medium and differentiated medium to investigate the markers of pro-inflammation, atrophy, and myogenesis. We found that melatonin regulated RASF CM-induced pathological muscle pro-inflammation and atrophy in myoblasts and differentiated myocytes through NF-κB signaling pathways. We also showed for the first time that miR-30c-1-3p is negatively regulated by three inflammatory cytokines in human RASF, which is associated with murine-differentiated myocytes. Importantly, oral administration with melatonin in a collagen-induced arthritis (CIA) mouse model also significantly improved arthritic swelling, hind limb grip strength as well as pathological muscle atrophy. In conclusion, our study is the first to demonstrate not only the underlying mechanism whereby melatonin decreases pro-inflammation in RA-induced pathological muscle atrophy but also increases myogenesis in myoblasts and differentiated myocytes.

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褪黑激素调节类风湿滑膜成纤维细胞相关炎症:病理骨骼肌治疗的意义》。
据报道,褪黑素可调节昼夜节律,并在各种炎症性自身免疫疾病中具有抗炎特性,但其在疾病相关肌肉萎缩中的作用仍存在争议。本研究旨在确定褪黑激素在类风湿性关节炎(RA)相关病理性肌肉萎缩中的作用证据。我们利用生物信息学的初步研究结果表明,褪黑激素能显著调节类风湿性关节炎滑膜成纤维细胞(RASF)和成肌细胞的促炎和肌生成之间的相关性。将褪黑素处理过的RASF的条件培养基(CM)与肌母细胞的生长培养基和分化培养基一起培养,以研究促炎、萎缩和肌生成的标志物。我们发现,褪黑激素可通过 NF-κB 信号通路调控 RASF CM 在成肌细胞和分化肌细胞中诱导的病理性肌肉促炎和萎缩。我们还首次发现,在人类 RASF 中,miR-30c-1-3p 受三种炎症细胞因子的负向调节,这与小鼠分化的肌细胞有关。重要的是,在胶原诱导的关节炎(CIA)小鼠模型中口服褪黑素也能显著改善关节炎肿胀、后肢握力以及病理性肌肉萎缩。总之,我们的研究首次证明了褪黑激素不仅能减少RA诱导的病理性肌肉萎缩中的促炎作用,还能增加成肌细胞和分化肌细胞的肌生成的内在机制。
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来源期刊
Journal of Pineal Research
Journal of Pineal Research 医学-内分泌学与代谢
CiteScore
17.70
自引率
4.90%
发文量
66
审稿时长
1 months
期刊介绍: The Journal of Pineal Research welcomes original scientific research on the pineal gland and melatonin in vertebrates, as well as the biological functions of melatonin in non-vertebrates, plants, and microorganisms. Criteria for publication include scientific importance, novelty, timeliness, and clarity of presentation. The journal considers experimental data that challenge current thinking and welcomes case reports contributing to understanding the pineal gland and melatonin research. Its aim is to serve researchers in all disciplines related to the pineal gland and melatonin.
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