PuSH - Publication Server of Helmholtz Zentrum München

Abe, T.* ; Shin, J.T.* ; Hosur, K.* ; Udey, M.C.* ; Chavakis, T.* ; Hajishengallis, G.*

Regulation of osteoclast homeostasis and inflammatory bone loss by MFG-E8.

J. Immunol. 193, 1383-1391 (2014)
DOI Order publishers version
Open Access Green as soon as Postprint is submitted to ZB.
The glycoprotein milk fat globule-epidermal 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-derived osteoclast precursors from MFG-E8-deficient (Mfge8(-/-)) mice underwent increased receptor activator of NF-κB ligand-induced osteoclastogenesis, leading to enhanced resorption pit formation compared with wild-type controls. Consistently, exogenously added MFG-E8 inhibited receptor activator of NF-κB ligand-induced 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(-/-) mice exhibited higher numbers of osteoclasts and more bone loss than did wild-type controls. Accordingly, local microinjection of anti-MFG-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(-/-) mice also experienced >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.
Altmetric
Additional Metrics?
Edit extra informations Login
Publication type Article: Journal article
Document type Scientific Article
ISSN (print) / ISBN 0022-1767
e-ISSN 1550-6606
Quellenangaben Volume: 193, Issue: 3, Pages: 1383-1391 Article Number: , Supplement: ,
Publisher American Association of Immunologists
Reviewing status Peer reviewed
Institute(s) Institute for Pancreatic Beta Cell Research (IPI)