{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T07:45:29Z","timestamp":1767080729813,"version":"3.48.0"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T00:00:00Z","timestamp":1767052800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"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>Shoulder stiffness (SS) is a common disease that causes pain and restricted range of motion (ROM), involving synovial inflammation and joint capsule fibrosis. The specific pathogenesis of SS remains unclear. This study aimed to delineate the key molecular driving capsule fibrosis in SS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Joint capsule samples from SS and non-SS patients were collected, and high-throughput RNA sequencing along with bioinformatic analysis were performed. A mouse SS model was established via joint immobilization. Functional and immunofluorescence assay were conducted on NIH3T3s. LY294002 was used both in NIH3T3s and mouse SS models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Transcriptomic analysis identified 100 differentially expressed genes (DEGs). Among the top hub genes, FGF9 was notably upregulated in the SS capsules.\n                      <jats:italic>In vitro<\/jats:italic>\n                      , FGF9 promoted NIH3T3s migration, proliferation, and \u03b1-SMA expression, effects that were reversed by LY294002.\n                      <jats:italic>In vivo<\/jats:italic>\n                      , intra-articular LY294002 injection reduced capsule thickening, fibrosis, and improved passive ROM in SS mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings revealed that FGF9 drove fibroblast activation and joint capsule fibrosis in SS via the PI3K\/Akt signaling pathway. Targeted inhibition of the PI3K\/Akt signaling might represent a promising therapeutic strategy for SS.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcell.2025.1731453","type":"journal-article","created":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T07:40:36Z","timestamp":1767080436000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Fibroblast growth factor 9 activates fibroblast activation and drives the progress of shoulder stiffness"],"prefix":"10.3389","volume":"13","author":[{"given":"Jian","family":"Xu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weihan","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunkang","family":"Kang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dongqiang","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanlong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenzhi","family":"Bi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haiyang","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beijie","family":"Qi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Biao","family":"Guo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,12,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e0215301","DOI":"10.1371\/journal.pone.0215301","article-title":"Fibroblast activation and inflammation in frozen shoulder","volume":"14","author":"Akbar","year":"2019","journal-title":"PLoS One"},{"key":"B2","doi-asserted-by":"publisher","first-page":"e039747","DOI":"10.1161\/JAHA.124.039747","article-title":"Persistent fibrosis in heart failure with a reduced ejection fraction linked to phenotypic differences in human cardiac fibroblast populations","volume":"14","author":"Biggs","year":"2025","journal-title":"J. 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