Duffy antigen receptor for chemokines regulates post-fracture inflammation.
Duffy antigen receptor for chemokines regulates post-fracture inflammation.
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DOI：
10.1371/journal.pone.0077362
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Edderkaoui B
中科院分区：
文献类型：
--
作者：
Rundle CH;Mohan S;Edderkaoui B
现在有相当多的实验数据表明，炎症细胞在骨骼骨折的愈合中合作。在骨折部位炎症细胞的募集机制方面，趋化因子及其受体受到了相当大的关注。我们以前的研究结果表明，达菲抗原趋化因子受体（Darc），非经典的趋化因子受体，不发出信号，而是作为一个清道夫的趋化因子，调节细胞迁移，是一个负调节剂的峰值骨密度在小鼠。此外，由于Darc由炎症细胞和内皮细胞表达，我们假设Darc作用的破坏将影响骨折后炎症，从而影响骨折愈合。为了验证这一假设，我们评估了具有靶向破坏Darc的小鼠和相应的野生型（WT）对照小鼠的骨折愈合。我们发现，与WT小鼠相比，Darc-KO小鼠术后7天的骨折骨痂软骨形成显著更大（33%）。与WT小鼠相比，增加的软骨与骨折后3天的胶原（Col）II表达和骨折后7天的Col-X表达相关，表明Darc缺乏导致早期骨折软骨形成和分化。然后，我们比较了已知在炎症过程中诱导的细胞因子和趋化因子基因的表达。在骨折后1天，Darc-KO小鼠的骨折中，白细胞介素（IL）-1β、IL-6和单核细胞趋化蛋白1均下调，这与炎症反应的改变一致。此外，与WT小鼠相比，Darc-KO中骨折周围的巨噬细胞数量显著减少。基于这些数据，我们得出结论，Darc在调节骨折的早期炎症反应和随后的软骨形成中起作用。然而，与WT小鼠相比，Darc-KO小鼠骨折部位的早期软骨形成并未转化为早期骨形成。
There is now considerable experimental data to suggest that inflammatory cells collaborate in the healing of skeletal fractures. In terms of mechanisms that contribute to the recruitment of inflammatory cells to the fracture site, chemokines and their receptors have received considerable attention. Our previous findings have shown that Duffy antigen receptor for chemokines (Darc), the non-classical chemokine receptor that does not signal, but rather acts as a scavenger of chemokines that regulate cell migration, is a negative regulator of peak bone density in mice. Furthermore, because Darc is expressed by inflammatory and endothelial cells, we hypothesized that disruption of Darc action will affect post-fracture inflammation and consequently will affect fracture healing. To test this hypothesis, we evaluated fracture healing in mice with targeted disruption of Darc and corresponding wild type (WT) control mice. We found that fracture callus cartilage formation was significantly greater (33%) at 7 days post-surgery in Darc-KO compared to WT mice. The increased cartilage was associated with greater Collagen (Col) II expression at 3 days post-fracture and Col-X at 7 days post-fracture compared to WT mice, suggesting that Darc deficiency led to early fracture cartilage formation and differentiation. We then compared the expression of cytokine and chemokine genes known to be induced during inflammation. Interleukin (Il)-1β, Il-6, and monocyte chemotactic protein 1 were all down regulated in the fractures derived from Darc-KO mice at one day post-fracture, consistent with an altered inflammatory response. Furthermore, the number of macrophages was significantly reduced around the fractures in Darc-KO compared to WT mice. Based on these data, we concluded that Darc plays a role in modulating the early inflammatory response to bone fracture and subsequent cartilage formation. However, the early cartilage formation was not translated with an early bone formation at the fracture site in Darc-KO compared to WT mice.
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影响因子：
2.8
作者：
Lange, Jeffrey;Sapozhnikova, Anna;Lu, Chuanyong;Hu, Diane;Li, Xin;Miclau, Theodore, III;Marcucio, Ralph S.
通讯作者：
Marcucio, Ralph S.
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影响因子：
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作者：
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通讯作者：
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作者：
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12.8
作者：
Jung, Young Su;Lee, Ha Young;Kim, Sang Doo;Park, Joon Seong;Kim, Jung Kuk;Suh, Pann-Ghill;Bae, Yoe-Sik
通讯作者：
Bae, Yoe-Sik
影响因子：
6.2
作者：
Cho, TJ;Gerstenfeld, LC;Einhorn, TA
通讯作者：
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