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基质细胞衍生因子-1/趋化因子受体-4通路介导外源性间充质干细胞在大鼠下颌骨牵张成骨中的募集

Recruitment of exogenous mesenchymal stem cells in mandibular distraction osteogenesis by the stromal cell-derived factor-1/chemokine receptor-4 pathway in rats.

作者信息

Cao Jian, Wang Lei, Du Zhao-jie, Liu Peng, Zhang Ya-bo, Sui Jian-fu, Liu Yan-pu, Lei De-lin

机构信息

Department of Oral and Maxillofacial Surgery, School of Stomatology, Fourth Military Medical University, Xi'an, China; Department of Oral and Maxillofacial Surgery, The Military General Hospital of Lanzhou Command, Lanzhou, China.

出版信息

Br J Oral Maxillofac Surg. 2013 Dec;51(8):937-41. doi: 10.1016/j.bjoms.2013.05.003. Epub 2013 Jun 6.

DOI:10.1016/j.bjoms.2013.05.003
PMID:23747231
Abstract

Distraction osteogenesis is widely used in orthopaedic and craniofacial surgery. However, its exact mechanism is still poorly understood. The purpose of this study was to find out whether there is systemic recruitment of mesenchymal stem cells (MSC) to the neocallus in the distraction gap by the stromal cell-derived factor-1 (SDF-1)/CXC chemokine receptor 4 (CXCR4) axis during osteogenesis. We examined the migration of MSC towards a gradient of SDF-1 in vitro. We also transplanted MSC labelled with green fluorescent protein (GFP) intravenously, with or without treatment with CXCR4-blocking antibody, into rats that had had unilateral mandibular distraction osteogenesis, and investigated the distribution of cells labelled with GFP in the soft callus after 24 h. We found that SDF-1 facilitated the migration potency of MSC both in vitro and in vivo, and this migration could be inhibited by AMD3100, an antagonist of CXCR4, and promoted by local infusion of exogenous SDF-1 into the distraction gap. This study provides a new insight into the molecular basis of how new bone is regenerated during distraction osteogenesis.

摘要

牵张成骨术在骨科和颅面外科中被广泛应用。然而,其确切机制仍未被充分理解。本研究的目的是探究在成骨过程中,是否存在通过基质细胞衍生因子-1(SDF-1)/CXC趋化因子受体4(CXCR4)轴将间充质干细胞(MSC)系统性募集至牵张间隙中的新骨痂。我们在体外检测了MSC向SDF-1梯度的迁移情况。我们还将标记有绿色荧光蛋白(GFP)的MSC静脉注射到进行单侧下颌骨牵张成骨术的大鼠体内,无论是否用CXCR4阻断抗体处理,24小时后研究GFP标记细胞在软骨痂中的分布。我们发现SDF-1在体外和体内均促进了MSC的迁移能力,且这种迁移可被CXCR4拮抗剂AMD3100抑制,并通过向牵张间隙局部注入外源性SDF-1而促进。本研究为牵张成骨过程中新骨如何再生的分子基础提供了新的见解。

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