Actin and ERK1/2-CEBPβ signaling mediates phagocytosis-induced innate immune response of osteoprogenitor cells.
Actin and ERK1/2-CEBPβ signaling mediates phagocytosis-induced innate immune response of osteoprogenitor cells.
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DOI：
10.1016/j.biomaterials.2011.08.059
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发表时间：
2011-12
期刊：
影响因子：
14
通讯作者：
Lee, Francis Youngin
中科院分区：
文献类型：
--
作者：
Lee, Heon Goo;Minematsu, Hiroshi;Kim, Kyung Ok;Aydemir, Ayse B. Celil;Shin, Mike J.;Nizami, Saqib A.;Chung, Kook Jin;Hsu, Anny C.;Jacobs, Christopher R.;Lee, Francis Youngin
宿主骨-植入物界面处的磨损颗粒是骨植入物关节置换术成功的主要挑战。目前对无菌性松动的理解包括巨噬细胞介导的炎症反应和破骨细胞生成增加，导致骨形成和吸收之间的失衡。尽管它在骨再生和种植体骨整合中起着重要作用，但近年来已经研究了骨祖细胞对磨损颗粒的反应。更具体地说，骨祖细胞介导的炎症的细胞内机制尚未完全阐明。在这项研究中，我们研究了骨祖细胞的作用和金属磨损颗粒引起炎症级联反应的细胞机制。通过体内和体外实验，我们已经证明了骨祖细胞能够通过吞噬磨损颗粒而引发炎症反应，这导致随后的巨噬细胞积聚和破骨细胞生成，并且ERK_CEBP/β细胞内信号传导是将磨损颗粒的吞噬与骨祖细胞中的炎症基因表达联系起来的关键炎症通路。AZD 6244治疗（ERK途径的有效抑制剂）在体内和体外均减弱了颗粒介导的炎性骨质溶解。本研究进一步加深了我们对骨祖细胞介导的炎症机制的理解，并为ERK_CEBP/β通路可能成为治疗炎性骨质溶解的合适靶点提供了进一步证据。
Wear particles at the host bone-implant interface are a major challenge for successful bone implant arthoplasties. Current understanding of aseptic loosening consists of macrophage-mediated inflammatory responses and increasing osteoclastogenesis, which lead to an imbalance between bone formation and resorption. Despite its significant role in bone regeneration and implant osteointegration, the osteoprogenitor response to wear particles has been examined recent years. More specifically, the intracellular mechanism of osteoprogenitor mediated inflammation has not been fully elucidated. In this study, we examined the role of osteoprogenitors and the cellular mechanism by which metal wear particles elicit an inflammatory cascade. Through both in vivo and in vitro experiments, we have demonstrated that osteoprogenitor cells are capable of initiating inflammatory responses by phagocytosing wear particles, which lead to subsequent accumulation of macrophages and osteoclastogenesis, and the ERK_CEBP/β intracellular signaling is a key inflammatory pathway that links phagocytosis of wear particles to inflammatory gene expression in osteoprogenitors. AZD6244 treatment, a potent inhibitor of the ERK pathway, attenuated particle mediated inflammatory osteolysis both in vivo and in vitro. This study advances our understanding of the mechanisms of osteoprogenitor-mediated inflammation, and provides further evidence that the ERK_CEBP/β pathway may be a suitable therapeutic target in the treatment of inflammatory osteolysis.
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DOI：
10.1302/0301-620x.79b3.7469
发表时间：
1997-05-01
影响因子：
--
作者：
Hukkanen, M;Corbett, SA;Polak, JM
通讯作者：
Polak, JM
影响因子：
11.4
作者：
AKIRA, S;ISSHIKI, H;KISHIMOTO, T
通讯作者：
KISHIMOTO, T
影响因子：
15.3
作者：
BIANCO, C;GRIFFIN, FM;SILVERSTEIN, SC
通讯作者：
SILVERSTEIN, SC
影响因子：
2.8
作者：
O'Connor, DT;Choi, MG;Sung, KLP
通讯作者：
Sung, KLP
影响因子：
2.8
作者：
Horowitz, SM;Gonzales, JB
通讯作者：
Gonzales, JB