{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T04:50:17Z","timestamp":1791521417399,"version":"4.3.4"},"reference-count":53,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T00:00:00Z","timestamp":1791504000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Osteoarthritis (OA) is a degenerative joint disease characterized by chronic inflammation and progressive cartilage destruction. Endothelial cell (EC) dysfunction contributes to inflammatory amplification in OA through increased vascular permeability and immune cell recruitment. This study aimed to characterize EC heterogeneity in OA and investigate the role of junctional adhesion molecule 2 (JAM2)-positive ECs in vascular dysfunction and macrophage adhesion.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Single-cell RNA sequencing data from the Gene Expression Omnibus database were analyzed to identify EC subpopulations in OA. JAM2 expression was validated in human OA synovium, meniscus, and subchondral bone using multiplex immunofluorescence staining. The effects of inflammatory cytokines, including TNF-\u03b1, IL-1\u03b2, IL-6, and TGF-\u03b21, on JAM2 expression in ECs were evaluated by qRT-PCR and immunofluorescence. The functional effects of JAM2 blockade on EC migration, tube formation, endothelial permeability, and monocyte adhesion were assessed using\n                      <jats:italic>in vitro<\/jats:italic>\n                      assays. The therapeutic potential of JAM2 blockade was further evaluated in a destabilization of the medial meniscus (DMM)-induced mouse model of OA.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      JAM2-positive ECs were enriched in pathways associated with cell adhesion and transendothelial migration. JAM2 expression was significantly increased in OA synovial tissue compared with controls. Among the inflammatory cytokines tested, TNF-\u03b1 most strongly upregulated JAM2 expression in ECs. TNF-\u03b1 stimulation impaired EC migration and tube formation, increased endothelial permeability, and enhanced monocyte adhesion, whereas JAM2 blockade partially attenuated these effects\n                      <jats:italic>in vitro<\/jats:italic>\n                      . In the DMM-induced OA model, JAM2 expression was increased in the vascular compartments of the synovium, meniscus, and subchondral bone, while JAM2 blockade attenuated cartilage degeneration and modulated macrophage infiltration.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>JAM2-positive ECs contribute to OA progression by promoting vascular dysfunction and macrophage adhesion. Targeting JAM2-positive ECs may represent a potential therapeutic strategy for alleviating chronic inflammation in OA.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcell.2026.1937741","type":"journal-article","created":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T04:25:45Z","timestamp":1791519945000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Single cell RNA-seq analysis identifies junctional adhesion molecule two positive endothelial cells aggravate osteoarthritis by mediating vascular permeability and macrophage adhesion"],"prefix":"10.3389","volume":"14","author":[{"given":"Yang","family":"Xing","sequence":"first","affiliation":[{"name":"Department of Joint Surgery, The First Affiliated Hospital of Sun Yat-Sen University","place":["Guangzhou, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengxin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Joint Surgery, The First Affiliated Hospital of Sun Yat-Sen University","place":["Guangzhou, Guangdong, China"]},{"name":"Department of Orthopaedics, South China Hospital, Medical School, Shenzhen University","place":["Shenzhen, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Joint Surgery, The First Affiliated Hospital of Sun Yat-Sen University","place":["Guangzhou, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linli","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Joint Surgery, The First Affiliated Hospital of Sun Yat-Sen University","place":["Guangzhou, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Puyi","family":"Sheng","sequence":"additional","affiliation":[{"name":"Department of Joint Surgery, The First Affiliated Hospital of Sun Yat-Sen University","place":["Guangzhou, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,10,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"H1838","DOI":"10.1152\/ajpheart.00026.2006","article-title":"Cardiac ischemia-reperfusion injury induces matrix metalloproteinase-2 expression through the AP-1 components FosB and JunB","volume":"291","author":"Alfonso-Jaume","year":"2006","journal-title":"Am. 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