Fan Qiqi, Wang Xuekui, Zhou Mengqi, Chen Yubei, Tao Dike, Rong Songxi, Zhou Shuang, Xue Hui, Sun Yao
Department of Oral Implantology, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Stomatological Hospital and Dental School of Tongji University, Shanghai 200072, China.
Department of Stomatology, Huashan Hospital of Fudan University, Shanghai 200040, China.
Fundam Res. 2022 Sep 19;5(4):1795-1803. doi: 10.1016/j.fmre.2022.09.006. eCollection 2025 Jul.
The indispensability of primary cilia in skeletal development has been widely recognized. We have previously shown that intraflagellar transport 140 (IFT140), a protein component of a bidirectional intraflagellar transport system required for ciliary function, controls bone development and dentinogenesis. However, it remains unknown whether IFT140 functionally contributes to bone fracture rehabilitation. Here an osteotomy-induced femoral fracture model was generated in -transgenic (-TG) and osteoblast-specific -conditional knockout (-cKO) mice. Micro-computed tomography, osteogenic induction, qualitative polymerase chain reaction, and toluidine blue and safranin O/fast green staining assays were used to characterize the dynamics of bone fracture healing from various perspectives. We found that IFT140 was relatively enriched in the bone callus and decreased in fracture-susceptible aged, or diabetic bones. -cKO mice had impaired osteogenic differentiation from bone mesenchymal stem cells, lower bone mass, and delayed fracture closure, whereas -TG mice had promising healing outcomes. Overall, our findings demonstrated for the first time that IFT140 has a beneficial role in fracture repair. Future investigation of the primary cilium in the context of aging and osteoporosis would certainly benefit patients at high risk of bone fractures.
原发性纤毛在骨骼发育中的不可或缺性已得到广泛认可。我们之前已经表明，鞭毛内运输蛋白140（IFT140）是纤毛功能所需的双向鞭毛内运输系统的一种蛋白质成分，它控制骨骼发育和牙本质形成。然而，IFT140是否在骨折修复中发挥功能作用仍不清楚。在此，我们在转基因（-TG）和成骨细胞特异性条件性敲除（-cKO）小鼠中建立了截骨诱导的股骨骨折模型。使用微型计算机断层扫描、成骨诱导、定性聚合酶链反应以及甲苯胺蓝和番红O/固绿染色分析，从多个角度表征骨折愈合的动态过程。我们发现IFT140在骨痂中相对富集，而在易骨折的老龄或糖尿病骨中减少。-cKO小鼠的骨间充质干细胞成骨分化受损、骨量较低且骨折愈合延迟，而-TG小鼠的愈合效果良好。总体而言，我们的研究结果首次证明IFT140在骨折修复中具有有益作用。未来在衰老和骨质疏松背景下对原发性纤毛的研究肯定会使骨折高危患者受益。
