{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T07:51:43Z","timestamp":1787730703359,"version":"build-2784847793"},"reference-count":18,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2023,5,11]],"date-time":"2023-05-11T00:00:00Z","timestamp":1683763200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100014903","name":"Osteo Science Foundation","doi-asserted-by":"publisher","award":["333466"],"award-info":[{"award-number":["333466"]}],"id":[{"id":"10.13039\/100014903","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["AG064003"],"award-info":[{"award-number":["AG064003"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["DE029709"],"award-info":[{"award-number":["DE029709"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["DE028715"],"award-info":[{"award-number":["DE028715"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["DE027851"],"award-info":[{"award-number":["DE027851"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Bone remodelling is mediated by orchestrated communication between osteoclasts and osteoblasts which, in part, is regulated by coupling and anti\u2010coupling factors. Amongst formally known anti\u2010coupling factors, Semaphorin 4D (Sema4D), produced by osteoclasts, plays a key role in downmodulating osteoblastogenesis. Sema4D is produced in both membrane\u2010bound and soluble forms; however, the mechanism responsible for producing sSema4D from osteoclasts is unknown. Sema4D, TACE and MT1\u2010MMP are all expressed on the surface of RANKL\u2010primed osteoclast precursors. However, only Sema4D and TACE were colocalized, not Sema4D and MT1\u2010MMP. When TACE and MT1\u2010MMP were either chemically inhibited or suppressed by siRNA, TACE was found to be more engaged in shedding Sema4D. Anti\u2010TACE\u2010mAb inhibited sSema4D release from osteoclast precursors by ~90%. Supernatant collected from osteoclast precursors (OC\u2010sup) suppressed osteoblastogenesis from MC3T3\u2010E1 cells, as measured by alkaline phosphatase activity, but OC\u2010sup harvested from the osteoclast precursors treated with anti\u2010TACE\u2010mAb restored osteoblastogenesis activity in a manner that compensates for diminished sSema4D. Finally, systemic administration of anti\u2010TACE\u2010mAb downregulated the generation of sSema4D in the mouse model of critical\u2010sized bone defect, whereas local injection of recombinant sSema4D to anti\u2010TACE\u2010mAb\u2010treated defect upregulated local osteoblastogenesis. Therefore, a novel pathway is proposed whereby TACE\u2010mediated shedding of Sema4D expressed on the osteoclast precursors generates functionally active sSema4D to suppress osteoblastogenesis.<\/jats:p>","DOI":"10.1111\/jcmm.17416","type":"journal-article","created":{"date-parts":[[2023,5,12]],"date-time":"2023-05-12T05:40:00Z","timestamp":1683870000000},"page":"1750-1756","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Soluble <scp>Sema4D<\/scp> cleaved from osteoclast precursors by <scp>TACE<\/scp> suppresses osteoblastogenesis"],"prefix":"10.1111","volume":"27","author":[{"given":"Takenobu","family":"Ishii","sequence":"first","affiliation":[{"name":"Department of Orthodontics Tokyo Dental College  Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Montserrat","family":"Ruiz\u2010Torruella","sequence":"additional","affiliation":[{"name":"Institut Sant Joan Carrer de Sant Joan  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae Young","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Prosthodontics Yonsei University Dental Hospital  Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3473-1218","authenticated-orcid":false,"given":"Hiroyuki","family":"Kanzaki","sequence":"additional","affiliation":[{"name":"Department of orthodontics, School of Dental Medicine Tsurumi University  Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdullah","family":"Albassam","sequence":"additional","affiliation":[{"name":"Department of Endodontics, Faculty of Dentistry King Abdulaziz University  Jeddah Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wichaya","family":"Wisitrasameewong","sequence":"additional","affiliation":[{"name":"Department of Periodontology Faculty of Dentistry Chulalongkorn University  Bangkok Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoru","family":"Shindo","sequence":"additional","affiliation":[{"name":"Department of Oral Science and Translational Research, College of Dental Medicine Nova Southeastern University  Fort Lauderdale Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roodelyne","family":"Pierrelus","sequence":"additional","affiliation":[{"name":"Department of Oral Science and Translational Research, College of Dental Medicine Nova Southeastern University  Fort Lauderdale Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alireza","family":"Heidari","sequence":"additional","affiliation":[{"name":"Department of Oral Science and Translational Research, College of Dental Medicine Nova Southeastern University  Fort Lauderdale Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Umadevi","family":"Kandalam","sequence":"additional","affiliation":[{"name":"Department of Oral Science and Translational Research, College of Dental Medicine Nova Southeastern University  Fort Lauderdale Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shin","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Department of Oral Science and Translational Research, College of Dental Medicine Nova Southeastern University  Fort Lauderdale Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandru","family":"Movila","sequence":"additional","affiliation":[{"name":"Department of Oral Science and Translational Research, College of Dental Medicine Nova Southeastern University  Fort Lauderdale Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dmitriy","family":"Minond","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy Nova Southeastern University  Fort Lauderdale Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3310-3818","authenticated-orcid":false,"given":"Toshihisa","family":"Kawai","sequence":"additional","affiliation":[{"name":"Department of Oral Science and Translational Research, College of Dental Medicine Nova Southeastern University  Fort Lauderdale Florida USA"},{"name":"Center for Collaborative Research, Cell Therapy Institute Nova Southeastern University  Fort Lauderdale Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,5,11]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-2776(03)81005-2"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1471-4906(01)02087-7"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2489"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-003-3257-7"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2012.05.026"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M609570200"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0606344104"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/JPER.18-0608"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.39086"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/imm.13189"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2016.10.012"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0150151"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ab.2007.04.043"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.10977"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1601114"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1097\/PRS.0b013e3181cb63a3"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2014.09.017"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-0-387-70956-7_10"}],"container-title":["Journal of Cellular and Molecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jcmm.17416","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,19]],"date-time":"2023-08-19T08:20:23Z","timestamp":1692433223000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jcmm.17416"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,11]]},"references-count":18,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2023,6]]}},"alternative-id":["10.1111\/jcmm.17416"],"URL":"https:\/\/doi.org\/10.1111\/jcmm.17416","archive":["Portico"],"relation":{},"ISSN":["1582-1838","1582-4934"],"issn-type":[{"value":"1582-1838","type":"print"},{"value":"1582-4934","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,11]]},"assertion":[{"value":"2022-01-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-05-03","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-05-11","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}