{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:30:48Z","timestamp":1787027448097,"version":"build-2736575974"},"reference-count":65,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2020,8,18]],"date-time":"2020-08-18T00:00:00Z","timestamp":1597708800000},"content-version":"am","delay-in-days":366,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#am"},{"start":{"date-parts":[[2019,8,18]],"date-time":"2019-08-18T00:00:00Z","timestamp":1566086400000},"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"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["R01AR061484"],"award-info":[{"award-number":["R01AR061484"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["R01AR062207"],"award-info":[{"award-number":["R01AR062207"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["1R01NS103931"],"award-info":[{"award-number":["1R01NS103931"]}],"id":[{"id":"10.13039\/100000001","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":[[2020,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterized by insulin deficiency, and patients with diabetes have an increased risk of bone fracture and significantly impaired fracture healing. Proinflammatory cytokine tumor necrosis factor\u2010alpha is significantly upregulated in diabetic fractures and is believed to underlie delayed fracture healing commonly observed in diabetes. Our previous genetic screen for the binding partners of progranulin (PGRN), a growth factor\u2010like molecule that induces chondrogenesis, led to the identification of tumor necrosis factor receptors (TNFRs) as the PGRN\u2010binding receptors. In this study, we employed several\n                    <jats:italic>in vivo<\/jats:italic>\n                    models to ascertain whether PGRN has therapeutic effects in diabetic fracture healing. Here, we report that deletion of PGRN significantly delayed bone fracture healing and aggravated inflammation in the fracture models of mice with T1DM. In contrast, recombinant PGRN effectively promoted diabetic fracture healing by inhibiting inflammation and enhancing chondrogenesis. In addition, both TNFR1 proinflammatory and TNFR2 anti\u2010inflammatory signaling pathways are involved in PGRN\u2010stimulated diabetic fracture healing. Collectively, these findings illuminate a novel understanding concerning the role of PGRN in diabetic fracture healing and may have an application in the development of novel therapeutic intervention strategies for diabetic and other types of impaired fracture healing.\n                  <\/jats:p>","DOI":"10.1111\/nyas.14208","type":"journal-article","created":{"date-parts":[[2019,8,19]],"date-time":"2019-08-19T00:35:23Z","timestamp":1566174923000},"page":"43-56","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Progranulin promotes diabetic fracture healing in mice with type 1 diabetes"],"prefix":"10.1111","volume":"1460","author":[{"given":"Jianlu","family":"Wei","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery New York University School of Medicine, New York University Medical Center  New York New York"},{"name":"Department of Orthopaedic Surgery Qilu Hospital of Shandong University  Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery New York University School of Medicine, New York University Medical Center  New York New York"},{"name":"Department of Orthopaedics, Shandong Provincial Qianfoshan Hospital the First Hospital Affiliated with Shandong First Medical University  Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanjing","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery New York University School of Medicine, New York University Medical Center  New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronghan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery New York University School of Medicine, New York University Medical Center  New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqi","family":"Guo","sequence":"additional","affiliation":[{"name":"College of Dentistry New York University  New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aubryanna","family":"Hettinghouse","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery New York University School of Medicine, New York University Medical Center  New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Buza","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery New York University School of Medicine, New York University Medical Center  New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean","family":"De La Croix","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery New York University School of Medicine, New York University Medical Center  New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Li","sequence":"additional","affiliation":[{"name":"College of Dentistry New York University  New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas A.","family":"Einhorn","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery New York University School of Medicine, New York University Medical Center  New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7181-8032","authenticated-orcid":false,"given":"Chuan\u2010ju","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery New York University School of Medicine, New York University Medical Center  New York New York"},{"name":"Department of Cell Biology New York University School of Medicine  New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,8,18]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2009.10.007"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.2337\/db16-0063"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00198-018-4650-2"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/MED.0b013e3282f1cba3"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00198-006-0253-4"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/00003086-199810001-00003"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2008.10.042"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1247663"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/nyas.13191"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2009.090148"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1199214"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.2001.16.6.1004"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2012.12.006"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.39816"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep20909"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2015.08.077"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2014-205779"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.09-144659"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2013.05.030"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jss.2007.09.013"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2011.03.720"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.1100020115"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.2003.18.9.1584"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature25013"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.3108"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.injury.2008.04.008"},{"key":"e_1_2_8_28_1","unstructured":"Ding Y. J.Wei A.Hettinghouse et\u00a0al.2017.Progranulin growth factor promotes diabetic bone healing. InORS 2017 Annual Meeting San Diego Convention Center."},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.312.5782.1874b"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201600261R"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2017.02.014"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.59"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-0669-7_14"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0812429"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep21115"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep20356"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1530\/JME-15-0075"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbspin.2014.10.001"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.15461"},{"key":"e_1_2_8_40_1","first-page":"3085","article-title":"Progranulin promotes colorectal cancer proliferation and angiogenesis through TNFR2\/Akt and ERK signaling pathways","volume":"5","author":"Yang D.","year":"2015","journal-title":"Am. J. Cancer Res."},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep07023"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13238-015-0213-x"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.38755"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000124227.00670.AB"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.12261"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2015.07.027"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2015.07.029"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2016.01.011"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF03343726"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.54.10.2875"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.2174\/1381612823666170125154915"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc15-0783"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.injury.2011.03.021"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.070115"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0099656"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11914-015-0286-8"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2009.02.004"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0092743"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2013.09.024"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2011.10.003"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.201500211"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aaf7704"},{"key":"e_1_2_8_63_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3003720"},{"key":"e_1_2_8_64_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-017-1485-8"},{"key":"e_1_2_8_65_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1600862"},{"key":"e_1_2_8_66_1","doi-asserted-by":"publisher","DOI":"10.1503\/jpn.150131"}],"container-title":["Annals of the New York Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fnyas.14208","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/nyas.14208","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/nyas.14208","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/nyaspubs.onlinelibrary.wiley.com\/doi\/am-pdf\/10.1111\/nyas.14208","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/nyaspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/nyas.14208","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,7]],"date-time":"2023-09-07T08:36:51Z","timestamp":1694075811000},"score":1,"resource":{"primary":{"URL":"https:\/\/nyaspubs.onlinelibrary.wiley.com\/doi\/10.1111\/nyas.14208"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,8,18]]},"references-count":65,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,1]]}},"alternative-id":["10.1111\/nyas.14208"],"URL":"https:\/\/doi.org\/10.1111\/nyas.14208","archive":["Portico"],"relation":{},"ISSN":["0077-8923","1749-6632"],"issn-type":[{"value":"0077-8923","type":"print"},{"value":"1749-6632","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,8,18]]},"assertion":[{"value":"2019-05-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-07-18","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-08-18","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}