Xiao Han, Yan An, Li Miao, Wang Linfeng, Xiang Jie
Department of Pediatric Orthopaedics, Hunan Children's Hospital, Changsha, Hunan, 410007, China; The Pediatric Academy of University of South China, Changsha, Hunan, 410007, China.
Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, 410008, China.
Biochem Biophys Res Commun. 2023 Jan 22;641:34-41. doi: 10.1016/j.bbrc.2022.12.010. Epub 2022 Dec 8.
Delayed fracture union and nonunion are common complications of fracture encountered, while Low-intensity pulsed ultrasound (LIPUS) can stimulate bone regeneration. Still, the underlying mechanism of LIPUS on bone regeneration has been poorly understood, which resulted in varied outcomes in the clinic. Therefore, figuring out the mechanism of LIPUS on bone regeneration can lay the foundation for better use of LIPUS in clinical bone regenerative therapies. In this study, we created transgenic mice to reveal the relationship between the periosteal cells' fate and the number of ciliated cells under the LIPUS stimulation. In vitro, we isolated the periosteal cell and aim to figure out the relationship between LIPUS and HDAC6-mediated ciliogenesis and find out a potential target for LIPUS-based bone regeneration strategies. The results showed that LIPUS promoted femoral bone defect regeneration and enhanced osteogenic differentiation of Prrx1 cells. However, these pro-effects were significantly weakened when the Prrx1 cell's primary cilia were knocked down. Besides, LIPUS stimulated the formation of Prrx1 cells' primary cilia in the bone defect microenvironment. In vitro, the results supported that LIPUS enhanced the osteogenic differentiation of Prrx1 cells through HDAC6-mediated ciliogenesis. In conclusion, λ LIPUS could promote the osteogenic differentiation of Prrx1 cells to stimulate bone regeneration and inhibit the expression of HDAC6 to increase the prevalence of primary cilia in Prrx1 cells. LIPUS could enhance the osteogenic differentiation of Prrx1 cells mainly through HDAC6-mediated ciliogenesis.
骨折延迟愈合和不愈合是常见的骨折并发症，而低强度脉冲超声（LIPUS）可以刺激骨再生。然而，LIPUS促进骨再生的潜在机制仍不清楚，这导致临床上出现了不同的结果。因此，弄清楚LIPUS促进骨再生的机制可为其在临床骨再生治疗中的更好应用奠定基础。在本研究中，我们构建了转基因小鼠以揭示在LIPUS刺激下骨膜细胞命运与纤毛细胞数量之间的关系。在体外，我们分离了骨膜细胞，旨在弄清楚LIPUS与HDAC6介导的纤毛发生之间的关系，并找到基于LIPUS的骨再生策略的潜在靶点。结果表明，LIPUS促进股骨骨缺损再生并增强Prrx1细胞的成骨分化。然而，当Prrx1细胞的初级纤毛被敲低时，这些促进作用显著减弱。此外，LIPUS在骨缺损微环境中刺激Prrx1细胞初级纤毛的形成。在体外，结果支持LIPUS通过HDAC6介导的纤毛发生增强Prrx1细胞的成骨分化。总之，LIPUS可促进Prrx1细胞的成骨分化以刺激骨再生，并抑制HDAC6的表达以增加Prrx1细胞中初级纤毛的数量。LIPUS主要通过HDAC6介导的纤毛发生增强Prrx1细胞的成骨分化。
