LGR4 acts as a key receptor for R-spondin 2 to promote osteogenesis through Wnt signaling pathway.
LGR4 acts as a key receptor for R-spondin 2 to promote osteogenesis through Wnt signaling pathway.
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DOI：
10.1016/j.cellsig.2016.04.010
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发表时间：
2016-08
影响因子：
4.8
通讯作者：
Chao-Juan Zhu;Xinfeng Zheng;Yuehua Yang;Bo Li;Yu-ren Wang;Shengdan Jiang;Lei-Sheng Jiang
中科院分区：
文献类型：
--
作者：
Chao-Juan Zhu;Xinfeng Zheng;Yuehua Yang;Bo Li;Yu-ren Wang;Shengdan Jiang;Lei-Sheng Jiang
R-响应素蛋白被认为是典型的WNT/β-连环蛋白信号通路的分泌型激动剂，富含亮氨酸重复序列的G-蛋白偶联受体被认为是R-响应素受体。R-Respondin 2(Rsp2)和LGR4在介导成骨过程中的潜在作用仍然知之甚少。在Ourin体外实验中，我们发现Rspo2可以通过激活Wnt信号通路促进MC3T3-E1细胞的成骨。然而，在LGR4功能中断的细胞中，Rsop2的这种作用消失了。同时，Rspo2显著抑制破骨细胞的形成，这种作用依赖于LGR4功能正常的成骨细胞的存在。在Ourin活体实验中，我们发现外源性RspO2的应用挽救了去卵巢小鼠的骨丢失，并改善了骨的微结构。Rsp2可能通过激活规范的Wnt/β-catenin信号通路对骨代谢起正向调节作用，而LGR4则是Rsp2促进成骨的关键受体。
R-spondin proteins are identified as secreted agonists of the canonical Wnt/β-catenin signaling pathway, and leucine-rich repeat-containing G-protein-coupled receptors (LGR) are recognized as R-spondin receptors. The potential role of R-spondin 2 (Rspo2) and LGR4 in mediating osteogenesis remains poorly understood. In ourin vitroexperiments, we found that Rspo2 could promote osteogenesis through activating the Wnt signaling pathway in MC3T3-E1 cells. However, this effect of Rsop2 disappeared in the cells with functional disruption of LGR4. Meanwhile, Rspo2 significantly inhibited osteoclastogenesis and this effect of Rspo2 was dependent on the presence of osteoblasts with normal function of LGR4. In ourin vivoexperiments, we found that application of exogenous Rspo2 rescued the bone loss and improved the microarchitecture of bone in OVX mice. Rspo2 could be a positive regulator of bone metabolism through activating the canonical Wnt/β-catenin signaling, and LGR4 acted as a key receptor for Rspo2 to promote osteogenesis.