Jeon Hyeran Helen, Kang Jessica, Li Jiahui Madelaine, Kim Douglas, Yuan Gongsheng, Almer Nicolette, Liu Min, Yang Shuying
Department of Orthodontics, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Department of Basic and Translational Sciences, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Life (Basel). 2022 Jul 29;12(8):1147. doi: 10.3390/life12081147.
Osteocytes are the main mechanosensory cells during orthodontic and physiologic bone remodeling. However, the question of how osteocytes transmit mechanical stimuli to biological responses remains largely unanswered. Intraflagellar transport (IFT) proteins are important for the formation and function of cilia, which are proposed to be mechanical sensors in osteocytes. In particular, IFT80 is highly expressed in mouse skulls and essential for ciliogenesis. This study aims to investigate the short- and long-term effects of IFT80 deletion in osteocytes on orthodontic bone remodeling and physiological bone remodeling in response to masticatory force. We examined 10-week-old experimental DMP1 CRE.IFT80 and littermate control DMP1 CRE.IFT80 mice. After 5 and 12 days of orthodontic force loading, the orthodontic tooth movement distance and bone parameters were evaluated using microCT. Osteoclast formation was assessed using TRAP-stained paraffin sections. The expression of sclerostin and RANKL was examined using immunofluorescence stain. We found that the deletion of IFT80 in osteocytes did not significantly impact either orthodontic or physiologic bone remodeling, as demonstrated by similar OTM distances, osteoclast numbers, bone volume fractions (bone volume/total volume), bone mineral densities, and the expressions of sclerostin and RANKL. Our findings suggest that there are other possible mechanosensory systems in osteocytes and anatomic limitations to cilia deflection in osteocytes in vivo.
骨细胞是正畸和生理性骨重塑过程中的主要机械感觉细胞。然而,骨细胞如何将机械刺激传递至生物学反应这一问题在很大程度上仍未得到解答。鞭毛内运输(IFT)蛋白对于纤毛的形成和功能很重要,而纤毛被认为是骨细胞中的机械传感器。特别是,IFT80在小鼠颅骨中高表达,并且对纤毛发生至关重要。本研究旨在探究骨细胞中IFT80缺失对正畸骨重塑和对咀嚼力的生理性骨重塑的短期和长期影响。我们检查了10周龄的实验性DMP1 CRE.IFT80小鼠和同窝对照DMP1 CRE.IFT80小鼠。在施加正畸力5天和12天后,使用显微CT评估正畸牙齿移动距离和骨参数。使用TRAP染色的石蜡切片评估破骨细胞形成。使用免疫荧光染色检查硬化蛋白和RANKL的表达。我们发现,骨细胞中IFT80的缺失对正畸或生理性骨重塑均无显著影响,这通过相似的正畸牙齿移动距离、破骨细胞数量、骨体积分数(骨体积/总体积)、骨矿物质密度以及硬化蛋白和RANKL的表达得以证明。我们的研究结果表明,骨细胞中存在其他可能的机械感觉系统,并且在体内骨细胞中纤毛偏转存在解剖学限制。