title: NF-κB RelB negatively regulates osteoblast differentiation and bone formation.
abstract: RelA-mediated NF-κB canonical signaling promotes mesenchymal progenitor cell (MPC) proliferation, but inhibits differentiation of mature osteoblasts (OBs) and thus negatively regulates bone formation. Previous studies suggest that NF-κB RelB may also negatively regulate bone formation through noncanonical signaling, but they involved a complex knockout mouse model, and the molecular mechanisms involved were not investigated. Here, we report that RelB(-/-) mice develop age-related increased trabecular bone mass associated with increased bone formation. RelB(-/-) bone marrow stromal cells expanded faster in vitro and have enhanced OB differentiation associated with increased expression of the osteoblastogenic transcription factor, Runt-related transcription factor 2 (Runx2). In addition, RelB directly targeted the Runx2 promoter to inhibit its activation. Importantly, RelB(-/-) bone-derived MPCs formed bone more rapidly than wild-type cells after they were injected into a murine tibial bone defect model. Our findings indicate that RelB negatively regulates bone mass as mice age and limits bone formation in healing bone defects, suggesting that inhibition of RelB could reduce age-related bone loss and enhance bone repair.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY, USA; Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY, USA.
authors.forename: Zhenqiang
authors.initials: Z
authors.lastname: Yao
authors.forename: Yanyun
authors.initials: Y
authors.lastname: Li
authors.forename: Xiaoxiang
authors.initials: X
authors.lastname: Yin
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Dong
authors.forename: Lianping
authors.initials: L
authors.lastname: Xing
authors.forename: Brendan F
authors.initials: BF
authors.lastname: Boyce
mesh_terms: D000818:Animals; D001483:Base Sequence; D001846:Bone Development / Q000502:physiology*; D002454:Cell Differentiation; D017931:DNA Primers; D005260:Female; D005434:Flow Cytometry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010006:Osteoblasts / Q000166:cytology*; D016133:Polymerase Chain Reaction; D051841:Transcription Factor RelB / Q000502:physiology*
chemical_list: D017931:DNA Primers; C497594:Relb protein, mouse; D051841:Transcription Factor RelB
keywords: BONE FORMATION; MESENCHYMAL PROGENITOR CELLS; NF-κB; OSTEOBLASTS; RELB