{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T04:29:54Z","timestamp":1787977794889,"version":"build-2784847793"},"reference-count":55,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,2,4]],"date-time":"2022-02-04T00:00:00Z","timestamp":1643932800000},"content-version":"am","delay-in-days":365,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#am"},{"start":{"date-parts":[[2021,2,4]],"date-time":"2021-02-04T00:00:00Z","timestamp":1612396800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["W81XWH\u201016\u20101\u20100482"],"award-info":[{"award-number":["W81XWH\u201016\u20101\u20100482"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["nyaspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of the New York Academy of Sciences"],"published-print":{"date-parts":[[2021,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Type 2 diabetes mellitus (T2DM) significantly increases bone fragility and fracture risk. Progranulin (PGRN) promotes bone fracture healing in both physiological and type 1 diabetic conditions. The present study aimed to investigate the role of PGRN in T2DM bone fracture healing. MKR mice (with an FVB\/N genetic background) were used as the T2DM model. Drill\u2010hole and Bonnarens and Einhorn models were used to investigate the role of PGRN in T2DM fracture healing\n                    <jats:italic>in vivo<\/jats:italic>\n                    . Primary bone marrow cells were isolated for molecular and signaling studies, and reverse transcription\u2010polymerase chain reaction, immunohistochemical staining, and western blotting were performed to assess PGRN effects\n                    <jats:italic>in vitro<\/jats:italic>\n                    . PGRN mRNA and protein expression were upregulated in the T2DM model. Local administration of recombinant PGRN effectively promoted T2DM bone fracture healing\n                    <jats:italic>in vivo<\/jats:italic>\n                    . Additionally, PGRN could induce anabolic metabolism during endochondral ossification through the TNFR2\u2013Akt and Erk1\/2 pathways. Furthermore, PGRN showed anti\u2010inflammatory activity in the T2DM bone regeneration process. These findings suggest that local administration of exogenous PGRN may be an alternative strategy to support bone regeneration in patients with T2DM. Additionally, PGRN might hold therapeutic potential for other TNFR\u2010related metabolic disorders.\n                  <\/jats:p>","DOI":"10.1111\/nyas.14568","type":"journal-article","created":{"date-parts":[[2021,2,7]],"date-time":"2021-02-07T22:06:21Z","timestamp":1612735581000},"page":"77-89","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Progranulin promotes bone fracture healing via TNFR pathways in mice with type 2 diabetes mellitus"],"prefix":"10.1111","volume":"1490","author":[{"given":"Yuanjing","family":"Ding","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery New York University Medical Center  New York New York"},{"name":"Department of Orthopaedic Surgery, Jinan Central Hospital, Cheeloo College of Medicine Shandong University  Jinan Shandong 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