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Ligaments are the primary regions of pathological new bone formation in AS. Here, it is demonstrated that ligament tissue\u2010derived extracellular vesicles (EVs) and their interleukin\u201017A (IL\u201017A) cargo mediate the communication between the tissue and other cells. The investigation revealed that IL\u201017A in EVs can activate the JAK\u2010STAT3 pathway, thereby stimulating the expression of MMP14 in AS ligament. Overexpression of MMP14 can lead to changes in the cytoskeleton and mechanical signaling of mesenchymal stem cells and other cells. These alterations in cellular cytoskeleton and mechanical signaling at ligament sites in patients with AS or in stem cells treated with EVs can result in pathological new bone formation. Finally, inhibiting IL\u201017A activity and EV endocytosis effectively controlled inflammation and pathological new bone formation. Overall, these data suggest that ligament\u2010derived EVs and the enclosed IL\u201017A have a potential role in driving pathological new bone formation in AS, and targeting EVs may therefore emerge as a novel approach to delaying ectopic ossification in AS.<\/jats:p>","DOI":"10.1002\/advs.202406876","type":"journal-article","created":{"date-parts":[[2024,9,23]],"date-time":"2024-09-23T03:17:23Z","timestamp":1727061443000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Extracellular Vesicles Derived from Ligament Tissue Transport Interleukin\u201017A to Mediate Ligament\u2010To\u2010Bone Crosstalk in Ankylosing Spondylitis"],"prefix":"10.1002","volume":"11","author":[{"given":"Kaiyang","family":"Wang","sequence":"first","affiliation":[{"name":"Division of Spine Surgery Department of Orthopedic Surgery Nanjing Drum Tower Hospital Affiliated Hospital of Medical School Nanjing University  Zhongshan Road 321 Nanjing 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