{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T00:29:16Z","timestamp":1784334556052,"version":"3.55.0"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2014,8,1]],"date-time":"2014-08-01T00:00:00Z","timestamp":1406851200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The glycoprotein milk fat globule\u2013epidermal growth factor factor 8 (MFG-E8) is expressed in several tissues and mediates diverse homeostatic functions. However, whether it plays a role in bone homeostasis has not been established. In this study, we show for the first time, to our knowledge, that osteoclasts express and are regulated by MFG-E8. Bone marrow\u2013derived osteoclast precursors from MFG-E8\u2013deficient (Mfge8\u2212\/\u2212) mice underwent increased receptor activator of NF-\u03baB ligand\u2013induced osteoclastogenesis, leading to enhanced resorption pit formation compared with wild-type controls. Consistently, exogenously added MFG-E8 inhibited receptor activator of NF-\u03baB ligand\u2013induced osteoclastogenesis from mouse or human osteoclast precursors. Upon induction of experimental periodontitis, an oral inflammatory disease characterized by loss of bone support of the dentition, Mfge8\u2212\/\u2212 mice exhibited higher numbers of osteoclasts and more bone loss than did wild-type controls. Accordingly, local microinjection of anti\u2013MFG-E8 mAb exacerbated periodontal bone loss in wild-type mice. Conversely, microinjection of MFG-E8 inhibited bone loss in experimental mouse periodontitis. In comparison with wild-type controls, Mfge8\u2212\/\u2212 mice also experienced &amp;gt;60% more naturally occurring chronic periodontal bone loss. In conclusion, MFG-E8 is a novel homeostatic regulator of osteoclasts that could be exploited therapeutically to treat periodontitis and perhaps other immunological disorders associated with inflammatory bone loss.<\/jats:p>","DOI":"10.4049\/jimmunol.1400970","type":"journal-article","created":{"date-parts":[[2014,6,24]],"date-time":"2014-06-24T08:09:20Z","timestamp":1403597360000},"page":"1383-1391","source":"Crossref","is-referenced-by-count":44,"title":["Regulation of Osteoclast Homeostasis and Inflammatory Bone Loss by MFG-E8"],"prefix":"10.1093","volume":"193","author":[{"given":"Toshiharu","family":"Abe","sequence":"first","affiliation":[{"name":"Department of Microbiology, School of Dental Medicine, University of Pennsylvania , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jieun","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Microbiology, School of Dental Medicine, University of Pennsylvania , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kavita","family":"Hosur","sequence":"additional","affiliation":[{"name":"Department of Microbiology, School of Dental Medicine, University of Pennsylvania , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark C","family":"Udey","sequence":"additional","affiliation":[{"name":"Center for Cancer Research, Dermatology Branch, National Cancer Institute, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Triantafyllos","family":"Chavakis","sequence":"additional","affiliation":[{"name":"Department of Medicine, Institute for Clinical Chemistry and Laboratory Medicine, Dresden University of Technology , 01307 Dresden ,","place":["Germany"]},{"name":"Department of Clinical Pathobiochemistry, Institute for Clinical Chemistry and Laboratory Medicine, Dresden University of Technology , 01307 Dresden ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Hajishengallis","sequence":"additional","affiliation":[{"name":"Department of Microbiology, School of Dental Medicine, University of Pennsylvania , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2014,8,1]]},"reference":[{"key":"2025030707254198200_r1","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1002\/jcb.22076","article-title":"SED1\/MFG-E8: a bi-motif protein that orchestrates diverse cellular interactions","volume":"106","author":"Raymond","year":"2009","journal-title":"J. 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