{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T06:02:07Z","timestamp":1779775327452,"version":"3.53.1"},"reference-count":55,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,5,17]],"date-time":"2026-05-17T00:00:00Z","timestamp":1778976000000},"content-version":"vor","delay-in-days":16,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["P30AR69655"],"award-info":[{"award-number":["P30AR69655"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["R01AR085590"],"award-info":[{"award-number":["R01AR085590"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Orthopaedic Research"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Achilles tendinopathy is a common musculoskeletal disorder. A frequent late\u2010stage manifestation is tendon heterotopic ossification (HO). Achilles HO forms predominantly via endochondral ossification, yet the cellular and molecular mechanisms underlying this pathologic condition remain elusive. Here, we analyzed surgically excised biopsy samples with symptomatic human Achilles tendons alongside non\u2010diseased Achilles tendon controls primarily from lower\u2010limb amputation donors to characterize the morphologic and mineralization patterns of the disease. Based on these analyses, we propose a stepwise endochondral model of Achilles HO that we term \u201ctenochondral ossification\u201d to emphasize the chondrogenic intermediate stage and its tendon origin. This process includes tendon\u2010to\u2010cartilage metaplasia, characterized by increased glycosaminoglycan content (Alcian blue\u2010positive matrix) and the appearance of chondrocyte\u2010like cells aligning the collagen fibers; some cells have substantial RUNX2 or SOX9 expression; subsequent mineralization of the metaplastic tissue, indicated by alkaline phosphatase immunoreactivity and neovessel ingrowth; osteoclast differentiation and resorption of the calcified metaplastic tissue; and new bone deposition on metaplastic tendon remnants accompanied by robust RUNX2 immunoactivity. Furthermore, TNC expression remains high in the metaplastic cartilage but diminishes at the mineralization front. Taken together, these data support a tendon\u2010origin, endochondral pathway for Achilles tendon HO and highlight stage\u2010specific therapeutic opportunities for treating or preventing Achilles tendinopathy and HO development and progression.<\/jats:p>","DOI":"10.1002\/jor.70226","type":"journal-article","created":{"date-parts":[[2026,5,17]],"date-time":"2026-05-17T09:18:02Z","timestamp":1779009482000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Identification of a Tenochondral Ossification Sequence Producing Heterotopic Ossification in Human Achilles Tendinopathy"],"prefix":"10.1002","volume":"44","author":[{"given":"Haiyin","family":"Li","sequence":"first","affiliation":[{"name":"Center for Musculoskeletal Research Rochester New York USA"},{"name":"Department of Orthopaedics University of Rochester Medical Center Rochester New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brendan","family":"Boyce","sequence":"additional","affiliation":[{"name":"Center for Musculoskeletal Research Rochester New York USA"},{"name":"Department of Pathology University of Rochester Medical Center Rochester New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Ulici","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Rochester Medical Center Rochester New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4324-0525","authenticated-orcid":false,"given":"David","family":"Ciufo","sequence":"additional","affiliation":[{"name":"Center for Musculoskeletal Research Rochester New York USA"},{"name":"Department of Orthopaedics University of Rochester Medical Center Rochester New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chike","family":"Cao","sequence":"additional","affiliation":[{"name":"Center for Musculoskeletal Research Rochester New York USA"},{"name":"Department of Orthopaedics University of Rochester Medical Center Rochester New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,17]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00563207"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1080\/09638280701785866"},{"key":"e_1_2_8_4_1","first-page":"45","article-title":"Heterotopic Ossification of Tendo Achilles: An Uncommon Clinical Entity","volume":"9","author":"Vaishya R.","year":"2019","journal-title":"Journal of Orthopaedic Case Reports"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.smhs.2022.03.003"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/military-2024-002759"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/CORR.0000000000001085"},{"issue":"368","key":"e_1_2_8_8_1","first-page":"368","article-title":"Post Traumatic Ossification of the Achilles Tendon","volume":"68","author":"Proctor M. 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