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艾灸通过促进ACSL1介导的自噬以降解骨关节炎中NLRP3来改善异常的软骨下骨重塑。

Moxibustion ameliorates abnormal subchondral bone remodeling by promoting ACSL1-mediated autophagy to degrade NLRP3 in osteoarthritis.

作者信息

Chen Xuelan, Fu Liping, Huang Yu, Liao Qing, Zou Binhua, Yuan Lixia, Liu Gang

机构信息

Department of Rehabilitation Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, China.

School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510515, Guangdong, China.

出版信息

Chin Med. 2025 Aug 11;20(1):125. doi: 10.1186/s13020-025-01182-2.

DOI:10.1186/s13020-025-01182-2
PMID:40790756
Abstract

BACKGROUND

Osteoarthritis (OA) is a joint disorder that is characterized, among other features, by abnormal subchondral bone remodeling. Moxibustion, a traditional Chinese medicine treatment, has a long history in the clinical treatment of osteoarthritis and has demonstrated significant efficacy. However, the impact mechanisms of moxibustion on subchondral bone in osteoarthritis have yet to be elucidated.

PURPOSE

This study investigated the specific effects and mechanisms of moxibustion on abnormal subchondral bone remodeling in OA.

METHODS

Anterior cruciate ligament transection (ACLT) surgery was performed on mice to establish an OA model, and moxibustion intervention for 4 weeks. The effects of moxibustion on knee osteoarthritis symptoms and walking ability were assessed by knee joint diameter measurement, von Frey test and footprint analysis. Micro-CT, TEM, immunofluorescence staining, and western blot were used to detect the contact between autophagy-lysosomal pathway and NLRP3 inflammasome in subchondral bone remodeling. Subsequently, proteomic analysis was performed on mouse subchondral bone.

RESULTS

We first discovered that moxibustion intervention effectively reduced inflammation in the subchondral bone, thereby balancing the activities of osteoblasts and osteoclasts. Moxibustion, with its warming and medicinal properties, significantly alleviated pain and swelling and enhanced walking ability in OA mice. The findings also suggested that moxibustion counteracted subchondral bone imbalance by inhibiting the activation of the NLRP3 inflammasome through increased autolysosome levels. Proteomic analysis and experimental validation revealed that moxibustion promoted ACSL1 expression to regulate autophagy in OA subchondral bone.

CONCLUSION

Our study elucidated the molecular mechanism by which moxibustion improved the inflammatory environment and abnormal subchondral bone remodeling in OA mice by activating ACSL1-mediated autophagy, providing the basis and new insights for  advancing moxibustion therapy in OA.

摘要

背景

骨关节炎(OA)是一种关节疾病,其特征包括软骨下骨重塑异常等。艾灸作为一种中医疗法,在骨关节炎的临床治疗中历史悠久且疗效显著。然而,艾灸对骨关节炎软骨下骨的影响机制尚未阐明。

目的

本研究探讨艾灸对OA软骨下骨异常重塑的具体作用及机制。

方法

对小鼠进行前交叉韧带横断(ACLT)手术以建立OA模型,并进行4周的艾灸干预。通过测量膝关节直径、von Frey试验和足迹分析评估艾灸对膝骨关节炎症状和行走能力的影响。采用Micro-CT、透射电子显微镜(TEM)、免疫荧光染色和蛋白质印迹法检测软骨下骨重塑过程中自噬-溶酶体途径与NLRP3炎性小体之间的联系。随后,对小鼠软骨下骨进行蛋白质组学分析。

结果

我们首次发现艾灸干预可有效减轻软骨下骨炎症,从而平衡成骨细胞和破骨细胞的活性。艾灸凭借其温热特性和药用价值,显著减轻了OA小鼠的疼痛和肿胀,并增强了其行走能力。研究结果还表明,艾灸通过提高自噬溶酶体水平抑制NLRP3炎性小体的激活,从而抵消软骨下骨的失衡。蛋白质组学分析和实验验证表明,艾灸促进ACSL1表达以调节OA软骨下骨的自噬。

结论

我们的研究阐明了艾灸通过激活ACSL1介导的自噬改善OA小鼠炎症环境和软骨下骨异常重塑的分子机制,为推进艾灸治疗OA提供了依据和新的见解。

相似文献

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本文引用的文献

1
Targeting the NLRP3 inflammasome as a novel therapeutic target for osteoarthritis.靶向NLRP3炎性小体作为骨关节炎的新型治疗靶点
Inflammopharmacology. 2025 Feb;33(2):461-484. doi: 10.1007/s10787-024-01629-2. Epub 2025 Jan 13.
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Osteoarthritis.骨关节炎
Lancet. 2025 Jan 4;405(10472):71-85. doi: 10.1016/S0140-6736(24)02322-5.
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Regulation of the NLRP3 inflammasome by autophagy and mitophagy.自噬和线粒体自噬对NLRP3炎性小体的调节
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Knee Osteoarthritis.膝关节骨关节炎。
Ann Intern Med. 2024 Sep;177(9):ITC129-ITC144. doi: 10.7326/ANNALS-24-01249. Epub 2024 Sep 10.
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Skeletal Muscle Composition, Power, and Mitochondrial Energetics in Older Men and Women With Knee Osteoarthritis.膝关节骨关节炎老年男性和女性的骨骼肌组成、力量和线粒体能量学。
Arthritis Rheumatol. 2024 Dec;76(12):1764-1774. doi: 10.1002/art.42953. Epub 2024 Aug 22.
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Trends and cross-country inequalities in the global burden of osteoarthritis, 1990-2019: A population-based study.全球骨关节炎负担的趋势和国家间不平等:基于人群的研究。
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Mechanical and structural properties of articular cartilage and subchondral bone in human osteoarthritic knees.人骨关节炎膝关节软骨和软骨下骨的机械和结构特性。
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GYY4137-induced p65 sulfhydration protects synovial macrophages against pyroptosis by improving mitochondrial function in osteoarthritis development.GYY4137诱导的p65巯基化通过改善骨关节炎发展过程中的线粒体功能保护滑膜巨噬细胞免于焦亡。
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A review of the research progress on Artemisia argyi Folium: botany, phytochemistry, pharmacological activities, and clinical application.艾蒿叶研究进展综述:植物学、植物化学、药理学活性及临床应用。
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Rapid Selenoprotein Activation by Selenium Nanoparticles to Suppresses Osteoclastogenesis and Pathological Bone Loss.硒纳米颗粒快速激活硒蛋白以抑制破骨细胞生成和病理性骨丢失。
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