{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T02:41:46Z","timestamp":1791081706676,"version":"4.1.0"},"reference-count":31,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T00:00:00Z","timestamp":1765756800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T00:00:00Z","timestamp":1765756800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Orthopaedic Research"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>\n                      Tendinopathy is a common degenerative tendon disorder, characterized by extracellular matrix disorganization and progressive fibrosis. While macrophages play a role in fibrosis in other tissues, their specific function in tendon fibrosis remains unclear. This study aims to investigate the involvement of M2\u2010polarized macrophages and their secretion of transforming growth factor\u2010\u03b21 (TGF\u2010\u03b21) in tendon fibrosis. A chronic Achilles tendinopathy rat model was established by combining repetitive acupuncture needle puncture with treadmill overuse. Immunofluorescence and molecular biology techniques were used to assess M2 macrophage infiltration, TGF\u2010\u03b21 expression, and JNK pathway activation. Pharmacological intervention was performed using GW2580 (CSF\u20101R antagonist), and genetic knockout experiments were conducted in a mouse model. Results showed that the model group exhibited disrupted collagen structure and fibrotic matrix deposition in the tendon, accompanied by significant accumulation of CD206\u207a M2 macrophages and elevated TGF\u2010\u03b21 expression. Immunofluorescence co\u2010localization revealed that TGF\u2010\u03b21 was primarily produced by CD206\u207a macrophages. Activation of the JNK signaling pathway was observed. GW2580 treatment significantly reduced M2 macrophage infiltration, suppressed TGF\u2010\u03b21 levels, and improved histological fibrosis scores. Genetic deletion of\n                      <jats:italic>Tgf\u2010\u03b21<\/jats:italic>\n                      in myeloid cells also alleviated fibrotic changes. In conclusion, M2 macrophage\u2010derived TGF\u2010\u03b21 plays a crucial role in tendon fibrosis by activating the JNK signaling pathway, suggesting its potential as a therapeutic target.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jor.70121","type":"journal-article","created":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T08:55:10Z","timestamp":1765788910000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["M2 Macrophage\u2010Derived TGF\u2010\u03b21 Drives Tendon Fibrosis in Rodent Tendinopathy Models"],"prefix":"10.1002","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3755-670X","authenticated-orcid":false,"given":"Mingyang","family":"An","sequence":"first","affiliation":[{"name":"Senior Department of Orthopaedics Chinese PLA General Hospital Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3017-4434","authenticated-orcid":false,"given":"Feng","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Sports Injury and Arthroscopic Surgery National Institute of Sports Medicine Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8561-0198","authenticated-orcid":false,"given":"Baiqing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Beijing DCN Orthopedic Hospital Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8126-825X","authenticated-orcid":false,"given":"Yidong","family":"Wu","sequence":"additional","affiliation":[{"name":"Senior Department of Orthopaedics Chinese PLA General Hospital Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4336-239X","authenticated-orcid":false,"given":"Kangkang","family":"Yu","sequence":"additional","affiliation":[{"name":"Senior Department of Orthopaedics Chinese PLA General Hospital Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-6046-6546","authenticated-orcid":false,"given":"Zhongyao","family":"Li","sequence":"additional","affiliation":[{"name":"Senior Department of Orthopaedics Chinese PLA General Hospital Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5949-9545","authenticated-orcid":false,"given":"Yujie","family":"Liu","sequence":"additional","affiliation":[{"name":"Senior Department of Orthopaedics Chinese PLA General Hospital Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6979-2526","authenticated-orcid":false,"given":"Chunbao","family":"Li","sequence":"additional","affiliation":[{"name":"Senior Department of Orthopaedics Chinese PLA General Hospital Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12,15]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/jisakos-2017-000164"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms252111846"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom10121666"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2024.109927"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202104469"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.12701\/yujm.2020.00458"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2021.108339"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41420-024-02247-1"},{"issue":"8","key":"e_1_2_9_10_1","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0161590","article-title":"Dose\u2010Related and Time\u2010Dependent Development of Collagenase\u2010Induced Tendinopathy in Rats","volume":"11","author":"Orfei C. 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