Natural Resources Institute Finland (Luke), Green Technology, FI-31600, Jokioinen, Finland.
Institute of Biomedicine, University of Turku, FI-20520, Turku, Finland.
Sci Rep. 2018 Jan 16;8(1):859. doi: 10.1038/s41598-018-19204-5.
Sperm flagellar protein 2 (SPEF2) is essential for motile cilia, and lack of SPEF2 function causes male infertility and primary ciliary dyskinesia. Cilia are pointing out from the cell surface and are involved in signal transduction from extracellular matrix, fluid flow and motility. It has been shown that cilia and cilia-related genes play essential role in commitment and differentiation of chondrocytes and osteoblasts during bone formation. Here we show that SPEF2 is expressed in bone and cartilage. The analysis of a Spef2 knockout (KO) mouse model revealed hydrocephalus, growth retardation and death prior to five weeks of age. To further elucidate the causes of growth retardation we analyzed the bone structure and possible effects of SPEF2 depletion on bone formation. In Spef2 KO mice, long bones (tibia and femur) were shorter compared to wild type, and X-ray analysis revealed reduced bone mineral content. Furthermore, we showed that the in vitro differentiation of osteoblasts isolated from Spef2 KO animals was compromised. In conclusion, this study reveals a novel function for SPEF2 in bone formation through regulation of osteoblast differentiation and bone growth.
精子鞭毛蛋白 2（SPEF2）对于运动纤毛是必需的，缺乏 SPEF2 功能会导致男性不育和原发性纤毛运动障碍。纤毛从细胞表面伸出，参与细胞外基质、流体流动和运动的信号转导。已经表明，纤毛和纤毛相关基因在骨形成过程中软骨细胞和成骨细胞的分化和分化中发挥重要作用。在这里，我们显示 SPEF2 在骨骼和软骨中表达。Spef2 敲除（KO）小鼠模型的分析显示，在 5 周龄之前出现脑积水、生长迟缓并死亡。为了进一步阐明生长迟缓的原因，我们分析了骨结构和 SPEF2 耗竭对骨形成的可能影响。在 Spef2 KO 小鼠中，长骨（胫骨和股骨）比野生型短，X 射线分析显示骨矿物质含量减少。此外，我们表明从 Spef2 KO 动物分离的成骨细胞的体外分化受损。总之，这项研究揭示了 SPEF2 通过调节成骨细胞分化和骨生长在骨形成中的新功能。
