{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T17:01:49Z","timestamp":1789146109539,"version":"build-2803163510"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T00:00:00Z","timestamp":1776384000000},"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. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Hyperlipidemia is a globally prevalent metabolic disorder, and the lipid metabolic dysregulation it induces is closely associated with the onset and progression of tendon pathologies, which are typically characterized by ECM dyshomeostasis, disorganized collagen fiber structure and impaired biomechanical properties in the affected tendons. The TGF-\n                      <jats:italic>\u03b2<\/jats:italic>\n                      signaling pathway serves as a central regulator of tendon ECM metabolic homeostasis, among which the TGF-\u03b2\/Smad2 axis can directly mediate the balanced regulation of collagen synthesis and degradation in tendons, yet its specific role and underlying molecular mechanism in hyperlipidemia-induced tendon ECM dysfunction remain poorly defined.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We examined how oxidized lipids affect the TGF-\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \/Smad2 signaling axis in tendon tissue. Specifically, we assessed T\u03b2RII localization within lipid rafts, TGF-\u03b2 activation, downstream transcription of Col1a1 and lysyl oxidase (LOX), and matrix metalloproteinase-1 (MMP-1) activity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Oxidized lipids disrupted T\n                      <jats:italic>\u03b2<\/jats:italic>\n                      RII localization in lipid rafts, leading to impaired TGF-\u03b2 activation. This suppressed Smad2 signaling, decreased Col1a1 transcription and LOX expression, and increased MMP-1 activity. Consequently, tendon collagen synthesis declined while degradation rose, undermining structural integrity and intrinsic repair capacity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Hyperlipidemia-driven suppression of the TGF-\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \/Smad2 axis is the critical mechanism linking metabolic dysregulation to tendon matrix failure. Restoring TGF-\u03b2\/Smad2 signaling represents a promising therapeutic strategy to mitigate hyperlipidemia-induced tendon damage and poor healing.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1820393","type":"journal-article","created":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T04:14:12Z","timestamp":1776399252000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Hyperlipidemia-induced metabolic dysregulation impairs tendon homeostasis: the role of TGF-\u03b2\/Smad2 signaling pathway in lipid-mediated extracellular matrix remodeling"],"prefix":"10.3389","volume":"13","author":[{"given":"Peiyang","family":"Shang","sequence":"first","affiliation":[{"name":"Department of Orthopaedics, Putuo Hospital, Shanghai University of Traditional Chinese Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renxuan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, Putuo Hospital, Shanghai University of Traditional Chinese Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Xia","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, Putuo Hospital, Shanghai University of Traditional Chinese Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, Putuo Hospital, Shanghai University of Traditional Chinese Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renhao","family":"Yang","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Department of Orthopedics, Sports Medicine Center, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingge","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, Putuo Hospital, Shanghai University of Traditional Chinese Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,17]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1056\/nejm199307013290104","article-title":"Effect on blood lipids of very high intakes of fiber in diets low in saturated fat and cholesterol","volume":"329","author":"Jenkins","year":"1993","journal-title":"N Engl J 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