{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,16]],"date-time":"2026-08-16T18:05:13Z","timestamp":1786903513164,"version":"build-2736575974"},"reference-count":76,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2016,8,17]],"date-time":"2016-08-17T00:00:00Z","timestamp":1471392000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,2,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:sec>\n                  <jats:title>\u2003<\/jats:title>\n                  <jats:p>Extensive or persistent calcium phosphate deposition within soft tissues after severe traumatic injury or major orthopedic surgery can result in pain and loss of joint function. The pathophysiology of soft tissue calcification, including dystrophic calcification and heterotopic ossification (HO), is poorly understood; consequently, current treatments are suboptimal. Here, we show that plasmin protease activity prevents dystrophic calcification within injured skeletal muscle independent of its canonical fibrinolytic function. After muscle injury, dystrophic calcifications either can be resorbed during the process of tissue healing, persist, or become organized into mature bone (HO). Without sufficient plasmin activity, dystrophic calcifications persist after muscle injury and are sufficient to induce HO. Downregulating the primary inhibitor of plasmin (\u03b12-antiplasmin) or treating with pyrophosphate analogues prevents dystrophic calcification and subsequent HO in vivo. Because plasmin also supports bone homeostasis and fracture repair, increasing plasmin activity represents the first pharmacologic strategy to prevent soft tissue calcification without adversely affecting systemic bone physiology or concurrent muscle and bone regeneration. \u00a9 2016 American Society for Bone and Mineral Research.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1002\/jbmr.2973","type":"journal-article","created":{"date-parts":[[2016,8,17]],"date-time":"2016-08-17T12:23:27Z","timestamp":1471436607000},"page":"294-308","source":"Crossref","is-referenced-by-count":46,"title":["Plasmin Prevents Dystrophic Calcification After Muscle Injury"],"prefix":"10.1093","volume":"32","author":[{"given":"Nicholas A","family":"Mignemi","sequence":"first","affiliation":[{"name":"Department of Orthopaedics and RehabilitationVanderbilt University Medical CenterNashvilleTNUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masato","family":"Yuasa","sequence":"additional","affiliation":[{"name":"Department of OrthopaedicsTokyo Medical Dental UniversityTokyoJapan"},{"name":"Department of Orthopaedics and RehabilitationVanderbilt University Medical CenterNashvilleTNUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Courtney E","family":"Baker","sequence":"additional","affiliation":[{"name":"School of MedicineVanderbilt University Medical CenterNashvilleTNUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie N","family":"Moore","sequence":"additional","affiliation":[{"name":"Department of PharmacologyVanderbilt University Medical CenterNashvilleTNUSA"},{"name":"Department of Orthopaedics and RehabilitationVanderbilt University Medical CenterNashvilleTNUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rivka C","family":"Ihejirika","sequence":"additional","affiliation":[{"name":"School of MedicineVanderbilt University Medical CenterNashvilleTNUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William K","family":"Oelsner","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics and RehabilitationVanderbilt University Medical CenterNashvilleTNUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher S","family":"Wallace","sequence":"additional","affiliation":[{"name":"School of MedicineVanderbilt University Medical CenterNashvilleTNUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshitaka","family":"Yoshii","sequence":"additional","affiliation":[{"name":"Department of OrthopaedicsTokyo Medical Dental UniversityTokyoJapan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Okawa","sequence":"additional","affiliation":[{"name":"Department of OrthopaedicsTokyo Medical Dental UniversityTokyoJapan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexey S","family":"Revenko","sequence":"additional","affiliation":[{"name":"Ionis PharmaceuticalsCarlsbadCAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A Robert","family":"MacLeod","sequence":"additional","affiliation":[{"name":"Ionis PharmaceuticalsCarlsbadCAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gourab","family":"Bhattacharjee","sequence":"additional","affiliation":[{"name":"Ionis PharmaceuticalsCarlsbadCAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joey V","family":"Barnett","sequence":"additional","affiliation":[{"name":"Department of PharmacologyVanderbilt University Medical CenterNashvilleTNUSA"},{"name":"School of MedicineVanderbilt University Medical CenterNashvilleTNUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herbert S","family":"Schwartz","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics and RehabilitationVanderbilt University Medical CenterNashvilleTNUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jay L","family":"Degen","sequence":"additional","affiliation":[{"name":"Department of Experimental HematologyCincinnati Children's HospitalCincinnatiOHUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew J","family":"Flick","sequence":"additional","affiliation":[{"name":"Department of Experimental HematologyCincinnati Children's HospitalCincinnatiOHUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin M","family":"Cates","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and ImmunologyVanderbilt University Medical CenterNashvilleTNUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan G","family":"Schoenecker","sequence":"additional","affiliation":[{"name":"Vanderbilt Center for Bone BiologyVanderbilt University Medical CenterNashvilleTNUSA"},{"name":"Department of PediatricsVanderbilt University Medical CenterNashvilleTNUSA"},{"name":"Department of Pathology, Microbiology, and ImmunologyVanderbilt University Medical CenterNashvilleTNUSA"},{"name":"Department of PharmacologyVanderbilt University Medical CenterNashvilleTNUSA"},{"name":"Department of Orthopaedics and RehabilitationVanderbilt University Medical CenterNashvilleTNUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2016,8,17]]},"reference":[{"key":"2024021014253512800_jbmr2973-bib-0001","doi-asserted-by":"crossref","first-page":"S10","DOI":"10.5435\/00124635-200600001-00004","article-title":"Combat orthopaedics: a view from the trenches","volume":"14","author":"Covey","year":"2006","journal-title":"J Am Acad Orthop 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