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首页> 外文期刊>Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research >NF-κB RelB negatively regulates osteoblast differentiation and bone formation
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NF-κB RelB negatively regulates osteoblast differentiation and bone formation

机译：NF-κBRelB负调节成骨细胞分化和骨形成

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摘要

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.
机译：RelA介导的NF-κB规范信号传导促进间充质祖细胞（MPC）增殖，但抑制成熟成骨细胞（OBs）分化，从而负面调节骨形成。先前的研究表明，NF-κBRelB也可能通过非经典信号负调控骨形成，但它们涉及复杂的基因敲除小鼠模型，并且未研究涉及的分子机制。在这里，我们报告RelB-/-小鼠发展与年龄相关的骨小梁增加与骨形成增加有关。 RelB-/-骨髓基质细胞在体外扩增更快，并具有增强的OB分化，与成骨细胞转录因子Runt相关转录因子2（Runx2）的表达增加有关。此外，RelB直接靶向Runx2启动子以抑制其激活。重要的是，将RelB-/-骨源性MPC注入鼠胫骨骨缺损模型后，其形成骨骼的速度比野生型细胞快。我们的发现表明，随着小鼠年龄的增长，RelB负调节骨骼质量，并限制骨骼在愈合的骨缺损中的形成，这表明抑制RelB可以减少与年龄有关的骨质流失并增强骨骼修复。

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