Low intensity pulsed ultrasound enhanced mesenchymal stem cell recruitment through stromal derived factor-1 signaling in fracture healing.
Low intensity pulsed ultrasound enhanced mesenchymal stem cell recruitment through stromal derived factor-1 signaling in fracture healing.
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DOI：
10.1371/journal.pone.0106722
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Cheung WH
中科院分区：
文献类型：
--
作者：
Wei FY;Leung KS;Li G;Qin J;Chow SK;Huang S;Sun MH;Qin L;Cheung WH
低强度脉冲超声（LIPUS）已被证明是有效的促进骨折愈合，但其潜在的机制并没有完全描绘。我们研究了LIPUS对间充质干细胞（MSC）募集的影响以及基质细胞衍生因子-1/C-X-C趋化因子受体4型（SDF-1/CXCR 4）通路在响应LIPUS刺激中的关键作用，这是骨折愈合的关键因素。在体外实验中，将分离的大鼠MSCs分为对照组和LIPUS组。在37°C下给予LIPUS治疗20分钟/天，持续3天。对照组给予假LIPUS治疗。处理后，定量细胞内CXCR 4 mRNA、SDF-1 mRNA和分泌的SDF-1蛋白水平，并在使用或不使用AMD 3100阻断SDF-1/CXCR 4通路的情况下评价MSC迁移。对于体内研究，将接受MSC心内给药的骨折的8周龄幼鼠分为LIPUS治疗组、LIPUS+ AMD 3100治疗组或溶剂对照组。通过离体荧光成像研究移植的MSC向骨折部位的迁移。检测骨折部位和血清中SDF-1蛋白水平。骨折愈合参数，包括骨痂形态，骨痂的微结构和愈合骨的生物力学性能进行了研究。体外实验结果表明，LIPUS可上调MSCs中SDF-1和CXCR 4的表达，并提高条件培养液中SDF-1蛋白水平。LIPUS促进MSCs迁移，AMD 3100部分抑制MSCs迁移。体内研究表明，LIPUS促进MSCs向骨折部位迁移，这与局部和血清SDF-1水平的增加、骨痂形成的改变、骨痂微结构和力学性能的改善有关;而SDF-1/CXCR 4信号通路的阻断减弱了LIPUS对骨折骨的作用。提示SDF-1介导的MSCs迁移可能是LIPUS影响骨折愈合的重要机制之一。
Low intensity pulsed ultrasound (LIPUS) has been proven effective in promoting fracture healing but the underlying mechanisms are not fully depicted. We examined the effect of LIPUS on the recruitment of mesenchymal stem cells (MSCs) and the pivotal role of stromal cell-derived factor-1/C-X-C chemokine receptor type 4 (SDF-1/CXCR4) pathway in response to LIPUS stimulation, which are essential factors in bone fracture healing. For in vitro study, isolated rat MSCs were divided into control or LIPUS group. LIPUS treatment was given 20 minutes/day at 37°C for 3 days. Control group received sham LIPUS treatment. After treatment, intracellular CXCR4 mRNA, SDF-1 mRNA and secreted SDF-1 protein levels were quantified, and MSCs migration was evaluated with or without blocking SDF-1/CXCR4 pathway by AMD3100. For in vivo study, fractured 8-week-old young rats received intracardiac administration of MSCs were assigned to LIPUS treatment, LIPUS+AMD3100 treatment or vehicle control group. The migration of transplanted MSC to the fracture site was investigated by ex vivo fluorescent imaging. SDF-1 protein levels at fracture site and in serum were examined. Fracture healing parameters, including callus morphology, micro-architecture of the callus and biomechanical properties of the healing bone were investigated. The in vitro results showed that LIPUS upregulated SDF-1 and CXCR4 expressions in MSCs, and elevated SDF-1 protein level in the conditioned medium. MSCs migration was promoted by LIPUS and partially inhibited by AMD3100. In vivo study demonstrated that LIPUS promoted MSCs migration to the fracture site, which was associated with an increase of local and serum SDF-1 level, the changes in callus formation, and the improvement of callus microarchitecture and mechanical properties; whereas the blockade of SDF-1/CXCR4 signaling attenuated the LIPUS effects on the fractured bones. These results suggested SDF-1 mediated MSCs migration might be one of the crucial mechanisms through which LIPUS exerted influence on fracture healing.
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影响因子：
120.1
作者：
De Clercq, E
通讯作者：
De Clercq, E
影响因子：
5.2
作者：
Guo, Y;Hangoc, G;Broxmeyer, HE
通讯作者：
Broxmeyer, HE
影响因子：
3.3
作者：
Furlani, Dario;Li, Wenzhong;Steinhoff, Gustav
通讯作者：
Steinhoff, Gustav
DOI：
10.1016/b978-0-12-398459-3.00011-3
发表时间：
2012
影响因子：
--
作者：
Cheng, Min;Qin, Gangjian
通讯作者：
Qin, Gangjian
影响因子：
4
作者：
Caplan, Arnold I.;Dennis, James E.
通讯作者：
Dennis, James E.