Identification of Mechanotransduction Pathways in Bone Formation induced by Low Intensity Pulsed Ultrasound

研究了低强度脉冲超声对大鼠骨髓细胞的合成代谢反应及其相关的机械转导途径。在原代培养的大鼠骨髓细胞和小鼠骨髓来源的ST2细胞中检测低强度脉冲超声辐照20min的效应。在有或无抗坏血酸的情况下培养的骨髓来源细胞在接受超声波照射前分别用地塞米松处理1、7和14天，以区分它们在不同发育阶段的反应。用RT-PCR方法检测IGF-I、骨钙素和包括c-fos、COX2等即刻早期基因在内的其他骨蛋白mRNAs的稳态水平。在ST2细胞中，我们已经报道的mRNA水平的上调(BBRC268：216,2000)只有在有限的条件下才能重现，这表明低强度的脉冲超声波只在成骨细胞系的早期阶段诱导细胞的合成代谢反应。我们的发现表明，某些细胞群对低强度脉冲超声的直接反应以旁分泌方式影响其他细胞，从而加速骨折修复的各个阶段。

Anabolic response to low-intensity, pulsed ultrasound and the associated mechanotransduction pathways were studied in rat bone marrow cells. Effects of 20-min exposure to low intensity, pulsed ultrasound were examined in both primary rat bone marrow cells and mouse bone marrow derived ST2 cells. The marrow-derived cells cultured in the presence and absence of ascorbate were treated with Dexamethazone for 1, 7, and 14 days prior to the exposure to the ultrasound so that their responses at different developmental stages can be distinguished. We determined the steady state levels of IGF-I, osteocalcin and other bone protein mRNAs including immediate early genes such as c-fos or cox 2 by using RT-PCR analysis. Upregulation of the mRNA levels that we have reported in ST2 cells (BBRC 268 : 216, 2000) was reproducible only under limited conditions, suggesting that the low intensity, pulsed ultrasound induce anabolic responses in cells only at early stages of osteogenic lineage. Our findings indicate that the direct reaction of certain population of cells to low intensity, pulsed ultrasound influences other cells in a paracrine manner resulting in acceleration of various phases of fracture repair.