{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T18:57:27Z","timestamp":1790708247628,"version":"4.1.0"},"reference-count":35,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"vor","delay-in-days":28,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"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":["Immunity Inflam &amp;amp; Disease"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Achieving rapid and high\u2010quality regeneration after injury at the tendon\u2010bone interface remains an urgent challenge in the fields of orthopedics, sports medicine, and tissue regeneration. Didymin (DID) possesses a range of pharmacological activities, including anti\u2010inflammatory, antioxidant, and antimicrobial properties; however, there is a research gap regarding the role of DID in tendon\u2010bone healing. Therefore, this study intends to further investigate the role of DID in tendon\u2010bone healing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A tendon\u2010bone healing mouse model of Achilles tendon\u2014Achilles bone was constructed, and the mice were treated with different doses of DID. The therapeutic effect of DID on tendon\u2010bone healing and its effect on macrophage polarization were investigated by evaluating various parameters such as tendon\u2010bone healing, fibrocartilage formation at the tendon\u2010bone interface, and macrophage polarization. In addition, in vitro experiments were used to verify whether the PPAR\u2010mediated fatty acid oxidation (FAO) pathway was involved in the induction of macrophage polarization by DID.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Treatment with DID was found to promote fibrocartilage formation in tendon\u2010bone junction tissues, ameliorate pathological injuries, induced macrophage polarization towards the M2 type, and downregulate the levels of IL\u20101\u03b2 and IL\u20106, while upregulating the levels of Arg1, IL\u201010, CoA, PPAR, and RXRA. However, the addition of a PPAR\u2010\u03b3 antagonist (GW9662) or an FAO inhibitor (Etomoxir) significantly attenuated the effects of DID on macrophage polarization.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study demonstrates that DID may enhance histological and molecular features of tendon\u2010bone healing partly through PPAR\u2010mediated fatty acid oxidation and macrophage M2 polarization, thereby facilitating tendon bone healing, with potential application value.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/iid3.70485","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T13:15:58Z","timestamp":1790687758000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Didymin may Enhance Tendon\u2010Bone Healing Partly by Promoting PPAR\u2010Mediated Fatty Acid Oxidation and Macrophage M2 Polarization"],"prefix":"10.1002","volume":"14","author":[{"given":"Xiaojun","family":"Ma","sequence":"first","affiliation":[{"name":"Sports Medicine Department, People's Hospital of Ningxia Hui Autonomous Region Third Clinical Medical College of Ningxia Medical University Yinchuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Shen","sequence":"additional","affiliation":[{"name":"Intensive Care Unit General Hospital of Ningxia Medical University Yinchuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Ma","sequence":"additional","affiliation":[{"name":"Sports Medicine Department, People's Hospital of Ningxia Hui Autonomous Region Third Clinical Medical College of Ningxia Medical University Yinchuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hangyu","family":"Li","sequence":"additional","affiliation":[{"name":"Sports Medicine Department, People's Hospital of Ningxia Hui Autonomous Region Third Clinical Medical College of Ningxia Medical University Yinchuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Li","sequence":"additional","affiliation":[{"name":"Sports Medicine Department, People's Hospital of Ningxia Hui Autonomous Region Third Clinical Medical College of Ningxia Medical University Yinchuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-9890-9505","authenticated-orcid":false,"given":"Jun","family":"Wan","sequence":"additional","affiliation":[{"name":"Sports Medicine Department, People's Hospital of Ningxia Hui Autonomous Region Third Clinical Medical College of Ningxia Medical University Yinchuan 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Y.","year":"2010","journal-title":"Lung Cancer"},{"key":"e_1_2_10_19_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.phrs.2021.105613","article-title":"Didymin Switches M1\u2010Like Toward M2\u2010Like Macrophage to Ameliorate Ulcerative Colitis via Fatty Acid Oxidation","volume":"169","author":"Lv Q.","year":"2021","journal-title":"Pharmacological Research"},{"key":"e_1_2_10_20_1","article-title":"Exosomes Derived From Bone Marrow Stromal Cells (BMSCs) Enhance Tendon\u2010Bone Healing by Regulating Macrophage Polarization","volume":"26","author":"Shi Y.","year":"2020","journal-title":"Medical Science Monitor"},{"key":"e_1_2_10_21_1","doi-asserted-by":"crossref","DOI":"10.3389\/fbioe.2022.823933","article-title":"Corrigendum: Disulfiram Suppressed Peritendinous Fibrosis Through Inhibiting Macrophage Accumulation and Its Pro\u2010Inflammatory Properties in Tendon Bone Healing","volume":"10","author":"Zhou Q.","year":"2022","journal-title":"Frontiers in Bioengineering and 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