作者:Guangxu He et al 来源:Bone Research 发布时间:2018/9/13 14:49:57
选择字号:
Wnt通路在Bmp调控松质骨与骨膜骨生长中的差异性作用

论文标题:Differential involvement of Wnt signaling in Bmp regulation of cancellous versus periosteal bone growth

期刊:Bone Research

作者:Guangxu He et al

发表时间: 2017/6/6

数字识别码:10.1038/boneres.2017.16

原文链接:https://www.nature.com/articles/boneres201716?utm_source=Other_website&utm_medium=Website_linksWebsite_links&utm_content=JesGuo-Nature-Bone_Research-Biology-China&utm_campaign=NROAAJ_USG_JRCN_JG_NROAAJ_Wnt

编辑总结

骨形态发生蛋白(Bmp)通过不同的机制调节不同类型骨组织的生长。虽然人们早已了解到Bmp可以调控骨和软骨的形成,但对其确切的机制仍知之甚少。美国华盛顿大学医学院的Fanxin Long及其同事曾发现,敲除某一特定Bmp受体后会导致松质骨(即骨骼中间的海绵状且代谢活跃的组织)形成过多,而骨组织最外层的骨膜骨形成不足。随后Long及其同事使用转基因小鼠研究了Bmp信号转导通路,发现Bmp通过两种不同的机制调节不同类型骨组织的形成。这些结果促进了我们对调控骨骼生长的信号转导机制的了解。

摘要

众所周知,骨形态发生蛋白(Bmp)可在在软骨形成后诱导骨形成,但Bmp信号通路在成骨细胞系中的直接作用尚不完全清楚。我们最近的研究表明,使用Dmp1-Cre敲除成骨细胞系中Bmpr1a受体后,总体上会降低成骨细胞的活性,但会刺激前成骨细胞的增殖,特别是在松质骨区域,导致骨膜骨生长减少与大量松质骨形成并存。硬化蛋白(SOST)是一种Wnt通路拮抗剂,由于在Bmpr1a缺陷的骨细胞中该蛋白的表达显著减少,因此我们采用遗传学方法验证了以下假设:Bmpr1a缺失导致的松质骨形成增加可能是由Wnt信号转导通路增强介导的。插入Dmp1启动子片段促使人SOST强制表达,可部分减轻Bmpr1a突变小鼠前成骨细胞的过度增殖和松质骨的过度生长,表明松质骨区室中Bmp和Wnt信号转导通路之间存在功能上的交互作用。为了检测Wnt信号通路增强是否能代偿Bmpr1a缺失引起的骨膜骨生长减少,我们构建了复合突变体,在原Bmpr1a突变小鼠中引入了Wnt受体Lrp5的过表达突变(A214V)。然而,结果发现突变的Lrp5并不能恢复Bmpr1a缺陷小鼠的骨膜骨生长。由此我们得出结论,Bmp通路通过诱导SOST分泌限制前成骨细胞增殖,从而减少了松质骨形成,但其促进骨膜骨生长的作用显然与Wnt通路活化无关。

SOST表达可以部分挽救由Bmpr1a缺失引起的松质骨过度形成,但对皮质骨形成减少无明显作用。

Abstract:

Bone morphogenetic proteins (Bmp) are well-known to induce bone formation following chondrogenesis, but the direct role of Bmp signaling in the osteoblast lineage is not completely understood. We have recently shown that deletion of the receptor Bmpr1a in the osteoblast lineage with Dmp1-Cre reduces osteoblast activity in general but stimulates proliferation of preosteoblasts specifically in the cancellous bone region, resulting in diminished periosteal bone growth juxtaposed with excessive cancellous bone formation. Because expression of sclerostin (SOST), a secreted Wnt antagonist, is notably reduced in the Bmpr1a-deficient osteocytes, we have genetically tested the hypothesis that increased Wnt signaling might mediate the increase in cancellous bone formation in response to Bmpr1a deletion. Forced expression of human SOST from a Dmp1 promoter fragment partially rescues preosteoblast hyperproliferation and cancellous bone overgrowth in the Bmpr1a mutant mice, demonstrating functional interaction between Bmp and Wnt signaling in the cancellous bone compartment. To test whether increased Wnt signaling can compensate for the defect in periosteal growth caused by Bmpr1a deletion, we have generated compound mutants harboring a hyperactive mutation (A214V) in the Wnt receptor Lrp5. However, the mutant Lrp5 does not restore periosteal bone growth in the Bmpr1a-deficient mice. Thus, Bmp signaling restricts cancellous bone accrual partly through induction of SOST that limits preosteoblast proliferation, but promotes periosteal bone growth apparently independently of Wnt activation.

阅读论文原文,请访问

https://www.nature.com/articles/boneres201716?utm_source=Other_website&utm_medium=Website_linksWebsite_links&utm_content=JesGuo-Nature-Bone_Research-Biology-China&utm_campaign=NROAAJ_USG_JRCN_JG_NROAAJ_Wnt

(来源:科学网)

 
 
 
特别声明:本文转载仅仅是出于传播信息的需要,并不意味着代表本网站观点或证实其内容的真实性;如其他媒体、网站或个人从本网站转载使用,须保留本网站注明的“来源”,并自负版权等法律责任;作者如果不希望被转载或者联系转载稿费等事宜,请与我们接洽。
 
 打印  发E-mail给: 
    
 
以下评论只代表网友个人观点,不代表科学网观点。

 
相关新闻 相关论文

图片新闻
有刺植物在中海拔比例最高 性别规范影响农业整体绩效
首枚虾类琥珀在“石探记博物科学馆”展出 科学家首次实现活细胞RNA标记
>>更多
 
一周新闻排行 一周新闻评论排行
 
编辑部推荐博文
 
论坛推荐