The Role of IFT140 in Osteogenesis of Adult Mice Long Bone
The Role of IFT140 in Osteogenesis of Adult Mice Long Bone
复制标题
IFT140在成年小鼠长骨成骨中的作用
DOI：
10.1369/0022155419847188
复制
发表时间：
2019-08-01
影响因子：
3.2
通讯作者：
Sun, Yao
中科院分区：
文献类型：
--
作者：
Tao, Dike;Xue, Hui;Sun, Yao
初级纤毛在骨骼发育中具有关键作用，初级纤毛的功能障碍引起骨骼纤毛病。鞭毛内转运（IFT）蛋白是纤毛信号转导的保守介质。已知IFT亚复合物A调节纤毛中的逆行IFT。作为IFT复合物A的核心蛋白，IFT 140已被证明与在人类中引起的严重骨骼纤毛病有关系。然而，IFT 140在骨形成中的作用和机制尚未系统地公开。为了进一步研究IFT140在成骨中的潜在作用，我们通过条件性缺失前成骨细胞中的IFT140建立了小鼠模型。成年敲除小鼠表现出侏儒表型，如短骨长度，骨量减少，骨矿物质沉积率降低。此外，通过IFFT 140缺失，几种成骨细胞标志物的表达降低，并且随着年龄的增长，骨丢失变得严重。这些结果表明，纤毛基因Ift140是必不可少的骨发育。
Primary cilia have a pivotal role in bone development and the dysfunctions of primary cilia cause skeletal ciliopathies. Intraflagellar transport (IFT) proteins are conserved mediators of cilium signaling. IFT sub-complex A is known to regulate retrograde IFT in the cilium. As a core protein of IFT complex A, IFT140 has been shown to have a relationship with serious skeletal ciliopathies caused in humans. However, the effects and mechanisms of IFT140 in bone formation have not been systematically disclosed. To further investigate the potential role of IFT140 in osteogenesis, we established a mouse model by conditional deletion of IFT140 in pre-osteoblasts. The adult knock-out mice exhibited dwarf phenotypes, such as short bone length, less bone mass, and decreased bone mineral apposition rate. In addition, by IFT140 deletion, the expressions of several osteoblastic markers were decreased and loss of bone became severe with aging. These results suggest that cilia gene Ift140 is essential in bone development.