Low-intensity pulsed ultrasound stimulation promotes osteoblast differentiation through hedgehog signaling
Low-intensity pulsed ultrasound stimulation promotes osteoblast differentiation through hedgehog signaling
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DOI：
10.1002/jcb.26418
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发表时间：
2018-06-01
影响因子：
4
通讯作者：
Sasaki, Akira
中科院分区：
文献类型：
--
作者：
Matsumoto, Kenichi;Shimo, Tsuyoshi;Sasaki, Akira
低强度脉冲超声（LIPUS）已被用作骨折愈合治疗的辅助手段，但其作用机制尚不清楚。我们报道了在骨折动态重建部位的成骨细胞中，声音刺猬（SHH）信号被激活。机械刺激是骨重建的关键因素，它与初级纤毛作为hedgehog信号的传感器有关。在这里，我们观察到，与对照组相比，LIPUS促进小鼠股骨骨折部位骨痂形成的雅阁与Gli2阳性细胞一致。免疫荧光分析表明，初级纤毛和纤毛/osterix双阳性成骨细胞的数量增加，在骨折部位的LIPUS。LIPUS不仅刺激MC 3 T3-E1细胞初级纤毛的数量和长度，还刺激MC 3 T3-E1细胞中纤毛蛋白、Ift 88 mRNA以及SHH、Gli1和Gli2的水平。进一步的实验表明，LIPUS刺激成骨分化的smoothened激动剂（SAG）治疗的存在。这些结果表明，LIPUS刺激成骨细胞的成骨分化和成熟的主要纤毛介导的激活刺猬信号。
Low-intensity pulsed ultrasound (LIPUS) has been used as an adjunct to fracture healing therapies, but the mechanisms underlying its action are not known. We reported that sonic hedgehog (SHH) signaling was activated in osteoblasts at the dynamic remodeling site of a bone fracture. Mechanical stimulation is a crucial factor in bone remodeling, and it is related to the primary cilia as a sensor of hedgehog signaling. Here we observed that LIPUS promoted callus formation in accord with Gli2-positive cells after 14 days at the mouse femur fractured site compared with a control group. An immunofluorescence analysis showed that the numbers of primary cilia and cilia/osterix double-positive osteoblasts were increased at the fracture site by LIPUS. LIPUS stimulated not only the number and the length of primary cilia, but also the levels of ciliated protein, Ift88 mRNA, and SHH, Gli1, and Gli2 in MC3T3-E1 cells. Further experiments revealed that LIPUS stimulated osteogenic differentiation in the presence of smoothened agonist (SAG) treatment. These results indicate that LIPUS stimulates osteogenic differentiation and the maturation of osteoblasts by a primary cilium-mediated activation of hedgehog signaling.