{"title":"源自脂肪组织的细胞外囊泡会加重与肥胖有关的颞下颌关节骨关节炎。","authors":"Baochao Li, Yuqin Jin, Bingqing Zhang, Tong Lu, Jialing Li, Jingzi Zhang, Yiwen Zhou, Yanyi Wang, Caixia Zhang, Yue Zhao, Huang Li","doi":"10.1002/ctm2.70029","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Introduction</h3>\n \n <p>Temporomandibular joint osteoarthritis (TMJ OA) is a major disease that affects maxillofacial health and is characterised by cartilage degeneration and subchondral bone remodelling. Obesity is associated with the exacerbation of pathological manifestations of TMJ OA. However, the underlying mechanism between adipose tissue and the TMJ axis remains limited.</p>\n </section>\n \n <section>\n \n <h3> Objectives</h3>\n \n <p>To evaluate the effects of obesity and the adipose tissue on the development of TMJ OA.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>The obesity-related metabolic changes in TMJ OA patients were detected by physical signs and plasma metabolites. The effects of adipose tissue-derived EVs (Ad-EVs) on TMJ OA was investigated through histological and cytological experiments as well as gene editing technology. Alterations of Ad-EVs in obese state were identified by microRNA-seq analysis and the mechanism by which EVs affect TMJ OA was explored in vitro and in vivo.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>Obesity and the related metabolic changes were important influencing factors for TMJ OA. Ad-EVs from obese mice induced marked chondrocyte apoptosis, cartilage matrix degradation and subchondral bone remodelling, which exacerbated the development of TMJ OA. Depletion of Ad-EVs secretion by knocking out the geranylgeranyl diphosphate synthase (<i>Ggpps</i>) gene in adipose tissue significantly inhibited the obesity-induced aggravation of TMJ OA. MiR-3074-5p played an important role in this process .</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>Our work unveils an unknown link between obese adipose tissue and TMJ OA. Targeting the Ad-EVs and the miR-3074-5p may represent a promising therapeutic strategy for obesity-related TMJ OA.</p>\n </section>\n \n <section>\n \n <h3> Key points</h3>\n \n <div>\n <ul>\n \n <li>High-fat-diet-induced obesity aggravate the progression of TMJ OA in mice.</li>\n \n <li>Obese adipose tissue participates in cartilage damage through the altered miRNA in extracellular vesicles.</li>\n \n <li>Inhibition of miR-3074-5p/SMAD4 pathway in chondrocyte alleviated the effect of HFD-EVs on TMJ OA.</li>\n </ul>\n </div>\n </section>\n </div>","PeriodicalId":10189,"journal":{"name":"Clinical and Translational Medicine","volume":"14 10","pages":""},"PeriodicalIF":7.9000,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11442491/pdf/","citationCount":"0","resultStr":"{\"title\":\"Adipose tissue-derived extracellular vesicles aggravate temporomandibular joint osteoarthritis associated with obesity\",\"authors\":\"Baochao Li, Yuqin Jin, Bingqing Zhang, Tong Lu, Jialing Li, Jingzi Zhang, Yiwen Zhou, Yanyi Wang, Caixia Zhang, Yue Zhao, Huang Li\",\"doi\":\"10.1002/ctm2.70029\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Introduction</h3>\\n \\n <p>Temporomandibular joint osteoarthritis (TMJ OA) is a major disease that affects maxillofacial health and is characterised by cartilage degeneration and subchondral bone remodelling. Obesity is associated with the exacerbation of pathological manifestations of TMJ OA. However, the underlying mechanism between adipose tissue and the TMJ axis remains limited.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Objectives</h3>\\n \\n <p>To evaluate the effects of obesity and the adipose tissue on the development of TMJ OA.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>The obesity-related metabolic changes in TMJ OA patients were detected by physical signs and plasma metabolites. The effects of adipose tissue-derived EVs (Ad-EVs) on TMJ OA was investigated through histological and cytological experiments as well as gene editing technology. Alterations of Ad-EVs in obese state were identified by microRNA-seq analysis and the mechanism by which EVs affect TMJ OA was explored in vitro and in vivo.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>Obesity and the related metabolic changes were important influencing factors for TMJ OA. Ad-EVs from obese mice induced marked chondrocyte apoptosis, cartilage matrix degradation and subchondral bone remodelling, which exacerbated the development of TMJ OA. Depletion of Ad-EVs secretion by knocking out the geranylgeranyl diphosphate synthase (<i>Ggpps</i>) gene in adipose tissue significantly inhibited the obesity-induced aggravation of TMJ OA. MiR-3074-5p played an important role in this process .</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusions</h3>\\n \\n <p>Our work unveils an unknown link between obese adipose tissue and TMJ OA. 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引用次数: 0
摘要
导言：颞下颌关节骨关节炎（TMJ OA）是一种影响颌面部健康的主要疾病，其特点是软骨退化和软骨下骨重塑。肥胖与颞下颌关节炎的病理表现加剧有关。然而，脂肪组织与颞下颌关节轴之间的内在机制仍然有限：评估肥胖和脂肪组织对颞下颌关节 OA 发病的影响：方法：通过体征和血浆代谢物检测颞下颌关节OA患者与肥胖相关的代谢变化。方法：通过体征和血浆代谢物检测颞下颌关节OA患者与肥胖相关的代谢变化，通过组织学和细胞学实验以及基因编辑技术研究脂肪组织衍生的EVs（Ad-EVs）对颞下颌关节OA的影响。通过microRNA-seq分析确定了肥胖状态下Ad-EVs的变化，并在体外和体内探讨了EVs影响颞下颌关节OA的机制：结果：肥胖及相关代谢变化是颞下颌关节OA的重要影响因素。来自肥胖小鼠的Ad-EVs诱导了明显的软骨细胞凋亡、软骨基质降解和软骨下骨重塑，这加剧了颞下颌关节OA的发展。通过敲除脂肪组织中的香叶基二磷酸合成酶（Ggpps）基因来减少 Ad-EVs 的分泌，能显著抑制肥胖引起的颞下颌关节 OA 的恶化。MiR-3074-5p在这一过程中发挥了重要作用：我们的研究揭示了肥胖脂肪组织与颞下颌关节损伤之间的未知联系。针对 Ad-EVs 和 miR-3074-5p 可能是治疗肥胖相关颞下颌关节 OA 的一种有前景的策略：要点：高脂饮食诱导的肥胖会加剧小鼠颞下颌关节 OA 的进展。肥胖脂肪组织通过改变细胞外囊泡中的 miRNA 参与软骨损伤。抑制软骨细胞中的 miR-3074-5p/SMAD4 通路可减轻 HFD-EVs 对颞下颌关节 OA 的影响。
Temporomandibular joint osteoarthritis (TMJ OA) is a major disease that affects maxillofacial health and is characterised by cartilage degeneration and subchondral bone remodelling. Obesity is associated with the exacerbation of pathological manifestations of TMJ OA. However, the underlying mechanism between adipose tissue and the TMJ axis remains limited.
Objectives
To evaluate the effects of obesity and the adipose tissue on the development of TMJ OA.
Methods
The obesity-related metabolic changes in TMJ OA patients were detected by physical signs and plasma metabolites. The effects of adipose tissue-derived EVs (Ad-EVs) on TMJ OA was investigated through histological and cytological experiments as well as gene editing technology. Alterations of Ad-EVs in obese state were identified by microRNA-seq analysis and the mechanism by which EVs affect TMJ OA was explored in vitro and in vivo.
Results
Obesity and the related metabolic changes were important influencing factors for TMJ OA. Ad-EVs from obese mice induced marked chondrocyte apoptosis, cartilage matrix degradation and subchondral bone remodelling, which exacerbated the development of TMJ OA. Depletion of Ad-EVs secretion by knocking out the geranylgeranyl diphosphate synthase (Ggpps) gene in adipose tissue significantly inhibited the obesity-induced aggravation of TMJ OA. MiR-3074-5p played an important role in this process .
Conclusions
Our work unveils an unknown link between obese adipose tissue and TMJ OA. Targeting the Ad-EVs and the miR-3074-5p may represent a promising therapeutic strategy for obesity-related TMJ OA.
Key points
High-fat-diet-induced obesity aggravate the progression of TMJ OA in mice.
Obese adipose tissue participates in cartilage damage through the altered miRNA in extracellular vesicles.
Inhibition of miR-3074-5p/SMAD4 pathway in chondrocyte alleviated the effect of HFD-EVs on TMJ OA.
期刊介绍：
Clinical and Translational Medicine (CTM) is an international, peer-reviewed, open-access journal dedicated to accelerating the translation of preclinical research into clinical applications and fostering communication between basic and clinical scientists. It highlights the clinical potential and application of various fields including biotechnologies, biomaterials, bioengineering, biomarkers, molecular medicine, omics science, bioinformatics, immunology, molecular imaging, drug discovery, regulation, and health policy. With a focus on the bench-to-bedside approach, CTM prioritizes studies and clinical observations that generate hypotheses relevant to patients and diseases, guiding investigations in cellular and molecular medicine. The journal encourages submissions from clinicians, researchers, policymakers, and industry professionals.
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