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NF‐κB RelB Negatively Regulates Osteoblast Differentiation and Bone Formation
Author(s) -
Yao Zhenqiang,
Li Yanyun,
Yin Xiaoxiang,
Dong Yufeng,
Xing Lianping,
Boyce Brendan F
Publication year - 2014
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.2108
Subject(s) - relb , runx2 , osteoblast , microbiology and biotechnology , chemistry , progenitor cell , transcription factor , bone marrow , bone morphogenetic protein 2 , stromal cell , cancer research , biology , immunology , nfkb1 , stem cell , in vitro , biochemistry , gene
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. © 2014 American Society for Bone and Mineral Research.