Effect of a CCR1 receptor antagonist on systemic trafficking of MSCs and polyethylene particle-associated bone loss.
Effect of a CCR1 receptor antagonist on systemic trafficking of MSCs and polyethylene particle-associated bone loss.
复制标题
DOI：
10.1016/j.biomaterials.2012.02.003
复制
发表时间：
2012-05
期刊：
影响因子：
14
通讯作者：
Goodman, Stuart B.
中科院分区：
文献类型：
--
作者：
Gibon, Emmanuel;Yao, Zhenyu;Rao, Allison J.;Zwingenberger, Stefan;Batke, Barbara;Valladares, Roberto;Smith, Robert L.;Biswal, Sandip;Gambhir, Sanjiv S.;Goodman, Stuart B.
颗粒相关假体周围骨溶解仍然是关节置换术中的主要问题。磨损颗粒诱导的炎症导致的持续骨丢失伴随着持续的骨修复尝试。先前我们表明，间充质干细胞（MSC）全身招募到骨暴露于超高分子量聚乙烯（UHMWPE）颗粒的连续输注。介导这一过程的趋化因子受体轴是未知的。我们测试了两个假设：（1）CCR1受体介导MSC向UHMWPE颗粒的全身募集，（2）募集的MSC能够分化为功能性成熟成骨细胞并减少颗粒相关的骨丢失。将裸鼠随机分为四组。使用微型泵将UHMWPE颗粒连续注入股骨干。通过左心室全身注射遗传修饰的鼠野生型报告MSC。非侵入性成像用于测定MSC迁移和骨密度。生物发光和免疫组织化学证实了报告细胞的趋化性和它们在注入颗粒的存在下分化成成熟的成骨细胞。注射CCR1拮抗剂减少了报告细胞向UHMWPE颗粒输注部位的募集，并增加了骨质溶解。CCR1似乎是在UHMWPE颗粒存在下MSC趋化性的关键受体。干扰CCR1会加剧颗粒诱导的骨丢失。
Particle-associated periprosthetic osteolysis remains a major issue in joint replacement. Ongoing bone loss resulting from wear particle-induced inflammation is accompanied by continued attempts at bone repair. Previously we showed that mesenchymal stem cells (MSCs) are recruited systemically to bone exposed to continuous infusion of ultra high molecular weight polyethylene (UHMWPE) particles. The chemokine-receptor axis that mediates this process is unknown. We tested two hypotheses: (1) the CCR1 receptor mediates the systemic recruitment of MSCs to UHMWPE particles and (2) recruited MSCs are able to differentiate into functional mature osteoblasts and decrease particle-associated bone loss. Nude mice were allocated randomly to four groups. UHMWPE particles were continuously infused into the femoral shaft using a micro-pump. Genetically modified murine wild type reporter MSCs were injected systemically via the left ventricle. Non-invasive imaging was used to assay MSC migration and bone mineral density. Bioluminescence and immunohistochemistry confirmed the chemotaxis of reporter cells and their differentiation into mature osteoblasts in the presence of infused particles. Injection of a CCR1 antagonist decreased reporter cell recruitment to the UHMWPE particle infusion site and increased osteolysis. CCR1 appears to be a critical receptor for chemotaxis of MSCs in the presence of UHMWPE particles. Interference with CCR1 exacerbates particle-induced bone loss.
登录
查看更多内容
影响因子：
1
作者：
Hernigou P;Poignard A;Zilber S;Rouard H
通讯作者：
Rouard H
影响因子：
4.1
作者：
Beamer, WG;Donahue, LR;Baylink, DJ
通讯作者：
Baylink, DJ
影响因子：
20.1
作者：
Huang J;Zhang Z;Guo J;Ni A;Deb A;Zhang L;Mirotsou M;Pratt RE;Dzau VJ
通讯作者：
Dzau VJ
影响因子：
5.2
作者：
Honczarenko, Marek;Le, Yi;Silberstein, Leslie E.
通讯作者：
Silberstein, Leslie E.
影响因子：
2.8
作者：
Al-Saffar, N;Revell, PA
通讯作者：
Revell, PA