Long-term administration of AMD3100, an antagonist of SDF-1/CXCR4 signaling, alters fracture repair.
Long-term administration of AMD3100, an antagonist of SDF-1/CXCR4 signaling, alters fracture repair.
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DOI：
10.1002/jor.22145
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发表时间：
2012-11
影响因子：
2.8
通讯作者：
Yellowley, Clare E.
中科院分区：
文献类型：
--
作者：
Toupadakis, Chrisoula A.;Wong, Alice;Genetos, Damian C.;Chung, Dai-Jung;Murugesh, Deepa;Anderson, Matthew J.;Loots, Gabriela G.;Christiansen, Blaine A.;Kapatkin, Amy S.;Yellowley, Clare E.
骨折愈合涉及快速干细胞和祖细胞迁移、归巢和分化。SDF-1（CXCL 12）被认为是CXCR 4阳性干细胞和祖细胞运输到缺血（缺氧）损伤部位的主要调节因子，并调节其随后分化为成熟的修复细胞。在这项研究中，我们研究了SDF-1/CXCR 4信号在骨折愈合中的作用，其中血管破裂导致缺氧和SDF-1表达。每天两次向小鼠注射AMD 3100、CXCR 4拮抗剂或溶剂，直至实施安乐死，目的是削弱干细胞向骨折部位的归巢和/或其分化。骨折愈合进行了评估，使用显微计算机断层扫描，组织学，定量PCR，和机械测试。AMD 3100给药导致透明软骨体积（第14天）、骨痂体积（第42天）和矿化骨体积（第42天）显著减少，并导致与软骨内骨化相关的基因表达减少，包括1型胶原α 1、2型胶原α 1、血管内皮生长因子、膜联蛋白A5、一氧化氮合酶2和雷帕霉素的机制靶点。我们的数据表明，SDF-1/CXCR 4信号可能通过调节干细胞和祖细胞的募集和/或分化在骨愈合中起着核心作用。
Fracture healing involves rapid stem and progenitor cell migration, homing, and differentiation. SDF-1 (CXCL12) is considered a master regulator of CXCR4-positive stem and progenitor cell trafficking to sites of ischemic (hypoxic) injury and regulates their subsequent differentiation into mature reparative cells. In this study, we investigated the role of SDF-1/CXCR4 signaling in fracture healing where vascular disruption results in hypoxia and SDF-1 expression. Mice were injected with AMD3100, a CXCR4 antagonist, or vehicle twice daily until euthanasia with the intent to impair stem cell homing to the fracture site and/or their differentiation. Fracture healing was evaluated using micro-computed tomography, histology, quantitative PCR, and mechanical testing. AMD3100 administration resulted in a significantly reduced hyaline cartilage volume (day 14), callus volume (day 42) and mineralized bone volume (day 42) and reduced expression of genes associated with endochondral ossification including collagen Type 1 alpha 1, collagen Type 2 alpha 1, vascular endothelial growth factor, Annexin A5, nitric oxide synthase 2, and mechanistic target of rapamycin. Our data suggest that the SDF-1/CXCR4 signaling plays a central role in bone healing possibly by regulating the recruitment and/or differentiation of stem and progenitor cells.
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DOI：
10.1016/j.biocel.2010.03.020
发表时间：
2010-07
影响因子：
4
作者：
Hosogane, Naobumi;Huang, Zhiping;Rawlins, Bernard A.;Liu, Xia;Boachie-Adjei, Oheneba;Boskey, Adele L.;Zhu, Wei
通讯作者：
Zhu, Wei
影响因子：
4.1
作者：
Baldik, Y;Diwan, AD;Murrell, GAC
通讯作者：
Murrell, GAC
DOI：
10.1111/j.1749-6632.2009.04967.x
发表时间：
2009-01-01
期刊：
HEMATOPOIETIC STEM CELLS VII
影响因子：
--
作者：
Crisan, Mihaela;Chen, Chien-Wen;Peault, Bruno
通讯作者：
Peault, Bruno
影响因子：
82.9
作者：
Ceradini, DJ;Kulkarni, AR;Gurtner, GC
通讯作者：
Gurtner, GC
影响因子：
4
作者：
Genetos, Damian C.;Toupadakis, Chrisoula A.;Raheja, Leah F.;Wong, Alice;Papanicolaou, Savvas E.;Fyhrie, David P.;Loots, Gabriela G.;Yellowley, Clare E.
通讯作者：
Yellowley, Clare E.