{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T22:08:21Z","timestamp":1793830101197,"version":"4.6.1"},"reference-count":65,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2020,6,22]],"date-time":"2020-06-22T00:00:00Z","timestamp":1592784000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AR62207"],"award-info":[{"award-number":["AR62207"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 DE21464"],"award-info":[{"award-number":["R01 DE21464"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 DE25681"],"award-info":[{"award-number":["R01 DE25681"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 DE26507"],"award-info":[{"award-number":["R01 DE26507"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Balancing the process of bone formation and resorption is important in the maintenance of healthy bone. Therefore, the discovery of novel factors that can regulate bone metabolism remains needed. Irisin is a newly identified hormone\u2010like peptide. Recent studies have reported the involvement of irisin in many physiological and pathological conditions with bone mineral density changes, including osteopenia and osteoporotic fractures. In this study, we generated the first line of Osx\u2010Cre:FNDC5\/irisin KO mice, in which FNDC5\/irisin was specifically deleted in the osteoblast lineage. Gene and protein expressions of irisin were remarkably decreased in bones but no significant differences in other tissues were observed in knockout mice. FNDC5\/irisin deficient mice showed a lower bone density and significantly delayed bone development and mineralization from early\u2010stage to adulthood. Our\u00a0phenotypical analysis exhibited decreased osteoblast\u2010related gene expression and increased osteoclast\u2010related gene expression in bone tissues, and reduced adipose tissue browning due to bone\u2010born irisin deletion. By harvesting and culturing MSCs from the knockout mice, we found that osteoblastogenesis was inhibited and osteoclastogenesis was increased. By using irisin stimulated wildtype primary cells as a gain\u2010of\u2010function model, we further revealed the effects and mechanisms of irisin on promoting osteogenesis and inhibiting osteoclastogenesis in vitro. In addition, positive effects of exercise, including bone strength enhancement and body weight loss were remarkably weakened due to irisin deficiency. Interestingly, these changes can be rescued by supplemental administration of recombinant irisin during exercise. Our study indicates that irisin plays an important role in bone metabolism and the crosstalk between bone and adipose tissue. Irisin represents a potential molecule for the prevention and treatment of bone metabolic diseases.<\/jats:p>","DOI":"10.1002\/jcp.29894","type":"journal-article","created":{"date-parts":[[2020,6,23]],"date-time":"2020-06-23T01:32:31Z","timestamp":1592875951000},"page":"664-676","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":68,"title":["Irisin deficiency disturbs bone metabolism"],"prefix":"10.1002","volume":"236","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8083-0212","authenticated-orcid":false,"given":"Xiaofang","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Oral &amp; Cranio\u2010Maxillofacial Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine Shanghai Key Laboratory of Stomatology  Shanghai China"},{"name":"Division of Oral Biology Tufts University School of Dental Medicine  Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangfen","family":"Li","sequence":"additional","affiliation":[{"name":"Division of Oral Biology Tufts University School of Dental Medicine  Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Oral Biology Tufts University School of Dental Medicine  Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Oral Biology Tufts University School of Dental Medicine  Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengjuan","family":"Tao","sequence":"additional","affiliation":[{"name":"Division of Oral Biology Tufts University School of Dental Medicine  Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuanju","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Surgery and Department of Cell Biology New York University School of Medicine  New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qisheng","family":"Tu","sequence":"additional","affiliation":[{"name":"Division of Oral Biology Tufts University School of Dental Medicine  Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guofang","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Oral &amp; Cranio\u2010Maxillofacial Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine Shanghai Key Laboratory of Stomatology  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jake J.","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Oral Biology Tufts University School of Dental Medicine  Boston Massachusetts"},{"name":"Department of Developmental, Molecular and Chemical Biology Tufts University School of Medicine  Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,6,22]]},"reference":[{"issue":"7","key":"e_1_2_9_2_1","first-page":"13086","article-title":"Impact of vitamin D correction on circulating irisin: A 12 month interventional study","volume":"9","author":"Al\u2010Daghri N. M.","year":"2016","journal-title":"International Journal of Clinical and Experimental Medicine"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00198-014-2673-x"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-981-13-3681-2_16"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10777"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.141"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.7972"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0085161"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.5405\/jmbe.1346"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-9120(97)00113-6"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/902186"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1516622112"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-02557-8"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11248-011-9581-z"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1177\/1925362118797737"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.11107.2"},{"issue":"6","key":"e_1_2_9_17_1","first-page":"2964","article-title":"Southern blot analysis of DNA extracted from formalin\u2010fixed pathology specimens","volume":"46","author":"Dubeau L.","year":"1986","journal-title":"Cancer Research"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-13-1053"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.4103\/sjamf.sjamf_35_18"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2013.09.008"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcna.2015.01.010"},{"key":"e_1_2_9_22_1","unstructured":"Grano M. Colaianni G. Cuscito C. Brunetti G. Colucci S. Cinti S. &Mori G.(2018).United States Patent No. US20180153960A1. Retrieved fromhttps:\/\/patents.google.com\/patent\/US20180153960A1\/en"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ab.2004.02.002"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2011.233"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00774-019-01043-7"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00223-018-0387-3"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.10.025"},{"key":"e_1_2_9_28_1","doi-asserted-by":"crossref","unstructured":"Klangjareonchai T. Nimitphong H. Saetung S. Bhirommuang N. Samittarucksa R. Chanprasertyothin S. \u2026Ongphiphadhanakul B.(2014).Circulating sclerostin and irisin are related and interact with gender to influence adiposity in adults with prediabetes [Research article].https:\/\/doi.org\/10.1155\/2014\/261545","DOI":"10.1155\/2014\/261545"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.3390\/medicina55080485"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep40505"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.1971"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI61209"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201700983RR"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.peptides.2018.03.018"},{"key":"e_1_2_9_35_1","volume-title":"Alkaline phosphatase","author":"McComb R. B.","year":"2013"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2017.11.072"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1101254"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201800178R"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2019.08.112"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/cen.12672"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12020-018-1814-y"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12020-017-1476-1"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep18732"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2013.12.029"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0011492"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-62703-989-5_9"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.02480"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-416015-6.00004-6"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.12659\/MSM.906293"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/bonekey.2013.215"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0100218"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.13490"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.20463\/jenb.2018.0011"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI17054"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcna.2014.03.007"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2008-1862"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00223-014-9945-5"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1101\/pdb.prot5080"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00223-018-0415-3"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbspin.2017.03.011"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.12463"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2018.05.013"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1038\/boneres.2016.56"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.3230"},{"issue":"11","key":"e_1_2_9_65_1","first-page":"1567","article-title":"The association of new inflammatory markers with type 2 diabetes mellitus and macrovascular complications: A preliminary study","volume":"18","author":"Zhang M.","year":"2014","journal-title":"European Review for Medical and Pharmacological Sciences"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.1097\/GME.0000000000001388"}],"container-title":["Journal of Cellular Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjcp.29894","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcp.29894","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jcp.29894","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcp.29894","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,18]],"date-time":"2023-08-18T22:51:55Z","timestamp":1692399115000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcp.29894"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,22]]},"references-count":65,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,1]]}},"alternative-id":["10.1002\/jcp.29894"],"URL":"https:\/\/doi.org\/10.1002\/jcp.29894","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.738195875.793576103","asserted-by":"object"}]},"ISSN":["0021-9541","1097-4652"],"issn-type":[{"value":"0021-9541","type":"print"},{"value":"1097-4652","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,22]]},"assertion":[{"value":"2020-03-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-06-12","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-06-22","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}