Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, China.
Clin Transl Med. 2024 Oct;14(10):e70029. doi: 10.1002/ctm2.70029.
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.
To evaluate the effects of obesity and the adipose tissue on the development of TMJ OA.
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.
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 .
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.
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.
颞下颌关节骨关节炎（TMJ OA）是一种主要的疾病，影响颌面健康，其特征是软骨退化和软骨下骨重塑。肥胖与 TMJ OA 病理表现的恶化有关。然而，脂肪组织与 TMJ 轴之间的潜在机制仍然有限。
评估肥胖和脂肪组织对 TMJ OA 发展的影响。
通过体格检查和血浆代谢物检测 TMJ OA 患者的肥胖相关代谢变化。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 EV（Ad-EVs）对 TMJ OA 的影响。通过 microRNA-seq 分析鉴定肥胖状态下 Ad-EVs 的变化，并在体外和体内探索 EV 影响 TMJ OA 的机制。
肥胖和相关代谢变化是 TMJ OA 的重要影响因素。肥胖小鼠的 Ad-EVs 诱导明显的软骨细胞凋亡、软骨基质降解和软骨下骨重塑，加剧了 TMJ OA 的发展。敲除脂肪组织中的香叶基香叶基二磷酸合酶（Ggpps）基因以耗尽 Ad-EVs 的分泌，可显著抑制肥胖引起的 TMJ OA 加重。miR-3074-5p 在这个过程中起着重要作用。
我们的工作揭示了肥胖脂肪组织与 TMJ OA 之间的一个未知联系。靶向 Ad-EVs 和 miR-3074-5p 可能代表一种针对肥胖相关 TMJ OA 的有前途的治疗策略。
高脂肪饮食诱导的肥胖加剧了小鼠 TMJ OA 的进展。肥胖脂肪组织通过细胞外囊泡中改变的 miRNA 参与软骨损伤。抑制软骨细胞中的 miR-3074-5p/SMAD4 通路减轻了 HFD-EVs 对 TMJ OA 的影响。
