Department of Implantology, School & Hospital of Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai, China.
J Histochem Cytochem. 2019 Aug;67(8):601-611. doi: 10.1369/0022155419847188. Epub 2019 Apr 29.
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.
初级纤毛在骨骼发育中起着关键作用，初级纤毛功能障碍会导致骨骼纤毛病变。鞭毛内运输（IFT）蛋白是纤毛信号传导的保守介质。已知 IFT 亚复合物 A 调节纤毛中的逆行 IFT。IFT140 作为 IFT 复合物 A 的核心蛋白，已被证明与人类严重的骨骼纤毛病变有关。然而，IFT140 在骨形成中的作用和机制尚未被系统揭示。为了进一步研究 IFT140 在成骨中的潜在作用，我们通过条件性删除前成骨细胞中的 IFT140 建立了一个小鼠模型。成年敲除小鼠表现出矮小表型，如骨长度缩短、骨量减少和骨矿物质沉积率降低。此外，IFT140 的缺失导致几个成骨细胞标志物的表达降低，并且随着年龄的增长，骨丢失变得更加严重。这些结果表明，纤毛基因 Ift140 对骨骼发育至关重要。
