Osteoblastic Wnts differentially regulate bone remodeling and the maintenance of bone marrow mesenchymal stem cells
Osteoblastic Wnts differentially regulate bone remodeling and the maintenance of bone marrow mesenchymal stem cells
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成骨细胞Wnts差异调节骨重塑和骨髓间充质干细胞的维持
DOI：
10.1016/j.bone.2012.12.052
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发表时间：
2013-07-01
期刊：
影响因子：
4.1
通讯作者：
Guo, Xizhi
中科院分区：
文献类型：
--
作者：
Wan, Yong;Lu, Cheng;Guo, Xizhi
Wnt信号在胚胎骨发育和出生后骨重塑中发挥重要作用，但Lip5和β -连环蛋白的不同遗传改变对骨特性的影响不一致。更重要的是，11735是否通过肠源性血清素调控局部或全局骨形成仍存在争议。本研究通过Wntless （Wls）基因失活，使Wnt的分泌消失，探讨了Wnt蛋白在成骨细胞生态位中的功能。与Lrp5和β -连环蛋白突变体相比，成骨细胞祖细胞中Wls的缺失导致严重的骨减少，在成骨细胞发生、破骨细胞发生和骨髓间充质干细胞（BMSCs）的维持方面存在更严重的缺陷。这些发现支持了Wnt/Lrp5信号通过成骨细胞Wnt对成骨细胞骨形成和破骨细胞骨吸收的多重作用局部调节骨量积累的观点。此外，成骨细胞wnt赋予骨髓间充质干细胞维持的生态位作用，为骨髓间充质干细胞生态位的定义提供了新的线索。(C) 2013爱思唯尔公司版权所有。
Wnt signaling has important roles in embryonic bone development and postnatal bone remodeling, but inconsistent impact on bone property is observed in different genetic alterations of Lip5 and beta-catenin. More importantly, it is still controversial whether 11735 regulate bone formation locally or globally through gut-derived serotonin. Here we explored the function of Wnt proteins in osteoblastic niche through inactivation of the Wntless (Wls) gene, which abrogates the secretion of Wnts. The depletion of Wls in osteoblast progenitor cells resulted in severe osteopenia with more profound defects in osteoblastogenesis, osteoclastogenesis and maintenance of bone marrow mesenchymal stem cells (BMSCs) compared to that observed in Lrp5 and beta-catenin mutants. These findings support the point of view that Wnt/Lrp5 signaling locally regulates bone mass accrual through multiple effects of osteoblastic Wnts on osteoblastic bone formation and osteoclastic bone resorption. Moreover, osteoblastic Wnts confer a niche role for maintenance of BMSCs, providing novel cues for the definition of BMSCs niche in bone marrow. (C) 2013 Elsevier Inc. All rights reserved.