Feng Chong, Wang Zi-Rou, Li Chen-Yu, Zhang Xiang-Yu, Wang Xin-Xing
Tianjin Institute of Environmental and Operational Medicine, Tianjin, 300050, China.
School and Hospital of Stomatology, Tianjin Medical University, Tianjin, 300070, China.
BMC Musculoskelet Disord. 2025 Jan 13;26(1):44. doi: 10.1186/s12891-025-08274-y.
Rheumatoid arthritis (RA) is a chronic autoimmune disease which afflicts about nearly 1% of global population. RA results in synovitis and cartilage/bone damage, even disability which aggravates the health burden. Many drugs are used to relieve RA, such as glucocorticoids (GCs), non-steroidal anti-inflammatory drugs (NSAIDs), and disease-modifying anti-rheumatic drugs (DMARDs) in the clinical treatment. However, present clinical drugs have various disadvantages such as poor bioavailability and short biological half-life and drug resistance, or adverse effects. A recent study showed autophagy modulation may be a novel strategy in the treatment of RA. 3-Methylademine (3-MA), is the most widely used autophagy inhibitor, which blocks autophagy at the initiation and maturation stages. The aim of this study is to evaluate the effect of 3-MA in collagen-induced-arthritis (CIA) mice and further elucidate how 3-MA attenuated inflammation, and cartilage/bone damage in arthritis.
An in-vivo mouse collagen-induced arthritis model was applied to compare differences in ankle destruction among control mice and CIA mice treated with or without 3-MA. Bone and cartilage destruction degree was evaluated by histology and micro-computed tomography (µCT). Further in-vivo assays utilized mouse serum samples to investigate inflammatory levels, oxidative levels, and bone resorption cytokines. At last, an immunofluorescence assay was applied to detect the autophagy level among the three groups.
The in-vivo mouse collagen-induced arthritis model showed that CIA mice revealed apparent hind paw and ankle swelling which was aggravated gradually along with time, while 3-MA treatment attenuated swelling gradually. µCT and histological results showed typical lesions in CIA group while 3-MA treatment alleviated arthritis-related destruction. Serum assay showed that 3-MA significantly reduced inflammatory cytokines levels, suppressed oxidative levels and bone resorption cytokines. Immunofluorescence assay revealed 3-MA significantly inhibited the abnormal autophagy level in CIA mouse ankle.
3-MA protects bone destruction in CIA-induced mice arthritis by anti-inflammatory effect and autophagy inhibition.
类风湿关节炎（RA）是一种慢性自身免疫性疾病，全球约有近1%的人口受其影响。RA会导致滑膜炎以及软骨/骨损伤，甚至残疾，加重了健康负担。在临床治疗中，许多药物被用于缓解RA，如糖皮质激素（GCs）、非甾体抗炎药（NSAIDs）和改善病情抗风湿药（DMARDs）。然而，目前的临床药物存在各种缺点，如生物利用度低、生物半衰期短、耐药性或不良反应。最近的一项研究表明，自噬调节可能是治疗RA的一种新策略。3-甲基腺嘌呤（3-MA）是最广泛使用的自噬抑制剂，它在起始和成熟阶段阻断自噬。本研究的目的是评估3-MA对胶原诱导性关节炎（CIA）小鼠的影响，并进一步阐明3-MA如何减轻关节炎中的炎症以及软骨/骨损伤。
应用体内小鼠胶原诱导性关节炎模型，比较对照小鼠与接受或未接受3-MA治疗的CIA小鼠踝关节破坏的差异。通过组织学和显微计算机断层扫描（µCT）评估骨和软骨破坏程度。进一步的体内试验利用小鼠血清样本研究炎症水平、氧化水平和骨吸收细胞因子。最后，应用免疫荧光试验检测三组的自噬水平。
体内小鼠胶原诱导性关节炎模型显示，CIA小鼠后爪和踝关节明显肿胀，并随时间逐渐加重，而3-MA治疗可逐渐减轻肿胀。µCT和组织学结果显示CIA组有典型病变，而3-MA治疗减轻了与关节炎相关的破坏。血清检测显示，3-MA显著降低炎症细胞因子水平，抑制氧化水平和骨吸收细胞因子。免疫荧光试验显示，3-MA显著抑制CIA小鼠踝关节异常的自噬水平。
3-MA通过抗炎作用和自噬抑制保护CIA诱导的小鼠关节炎中的骨破坏。
