Clinical and Translational Medicine (Oct 2024)

Adipose tissue‐derived extracellular vesicles aggravate temporomandibular joint osteoarthritis associated with obesity

  • Baochao Li,
  • Yuqin Jin,
  • Bingqing Zhang,
  • Tong Lu,
  • Jialing Li,
  • Jingzi Zhang,
  • Yiwen Zhou,
  • Yanyi Wang,
  • Caixia Zhang,
  • Yue Zhao,
  • Huang Li

DOI
https://doi.org/10.1002/ctm2.70029
Journal volume & issue
Vol. 14, no. 10
pp. n/a – n/a

Abstract

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Abstract Introduction 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.

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