The effect of Lipoxin A4 on the interaction between macrophage and osteoblast: possible role in the treatment of aseptic loosening.
The effect of Lipoxin A4 on the interaction between macrophage and osteoblast: possible role in the treatment of aseptic loosening.
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DOI：
10.1186/1471-2474-10-57
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发表时间：
2009-06-02
影响因子：
2.3
通讯作者：
Ye D
中科院分区：
文献类型：
--
作者：
Li G;Wu P;Xu Y;Yu Y;Sun L;Zhu L;Ye D
无菌性松动（AL）是植入永久性假体的全关节置换（TJR）的主要问题。体外和体内研究已经清楚地表明，磨损碎屑及其副产物可能引发种植体周围组织的炎症。脂氧素（LX）是在炎症部位由花生四烯酸（AA）局部合成的内源性类花生酸，并介导促消退活性。大量的研究已经证实LXA_4在不同的细胞和动物模型中具有抗炎作用，但目前还没有关于LXA_4在AL发生发展或预防中作用的相关报道。建立了两种细胞系的共培养模型。为探讨外源性脂氧素A4（LXA 4）对聚甲基丙烯酸甲酯（PMMA）诱导的炎症反应的影响，采用ELISA试剂盒检测5日龄小鼠颅骨中TNF-α、IL-1β、PGE 2和GM-CSF等促炎细胞因子的含量，并通过钙释放测定骨吸收。为了进一步确定LXA 4的内源性作用，将细胞共培养，并且用或不用15-脂氧合酶（15-LO）siRNA阻断。采用实时荧光定量PCR和Western blotting检测15-LO的抑制效果。0.1 mg/ml、0.5 mg/ml和1.0 mg/ml PMMA显示出时间依赖性的方式来触发所研究的所有促炎细胞因子的产生。外源性0-100 nM LXA 4对上述细胞因子的产生和PMMA刺激的颅骨骨吸收均有抑制作用，且呈剂量依赖性。在单独培养的巨噬细胞和未单独培养的巨噬细胞的上清液中均未检测到LXA 4。在PMMA刺激的共培养细胞中，LXA 4表达显著增加，而15-LO siRNA可部分抑制LXA 4的表达。当用15-LO siRNA阻断LXA 4生成时，PMMA诱导的促炎细胞因子升高，骨吸收加速。在本研究中，我们证明了LXA 4在巨噬细胞和OB共培养系统中对PMMA诱导的炎症具有良好的抑制作用。
Aseptic loosening (AL) is the main problem of total joints replacement (TJR) by the implantation of permanently prosthetic components. In vitro and in vivo studies have clearly demonstrated that wear debris and its byproducts could trigger inflammation in the peri-implant tissue. Lipoxins (LXs) are endogenous eicosanoids synthesized locally from arachidonate acid (AA) at sites of inflammation and mediate pro-resolving activity. A number of studies have demonstrated the effect of LXA4 to counteract inflammation in different cell and animal models, but till now, no relative report about the role of LXs in progress or prevention of AL. Murine RAW264.7 macrophage cell line and MC3T3-E1 osteoblasts (OB) cell line were purchased. Co-cultured model of these two cell lines was established. To explore the effect of exogenous Lipoxin A4 (LXA4) on polymethylmethacrylate (PMMA) induced inflammation, pro-inflammatory cytokines including TNF-α, IL-1β, PGE2 and GM-CSF were measured by ELISA kits and bone resorption was quantified by measuring calcium release from 5-day-old mice calvaria in vitro. To determine further the endogenous effect of LXA4, cells were co-cultured and with or without 15-lipoxygease (15-LO) blocking by 15-LO siRNA. Both real-time PCR and western blotting were applied to confirm the inhibitory efficiency of 15-LO by siRNA. 0.1 mg/ml, 0.5 mg/ml and 1.0 mg/ml PMMA showed a time-dependent manner to trigger production of all the pro-inflammatory cytokines studied. Exogenous 0–100 nM LXA4 presented an inhibitory effect on both generation of above cytokines and PMMA stimulated calvarial bone resorption with a dose-dependent manner. LXA4 in supernatant from neither rest macrophages nor macrophages cultured alone exposing to PMMA was detectable. In co-cultured cells challenged by PMMA, LXA4 was increased significantly, while, this enhance could be partly inhibited by 15-LO siRNA. When LXA4 generation was blocked with 15-LO siRNA, the PMMA induced pro-inflammatory cytokines were elevated and bone resorption was accelerated. In the present study, we demonstrated that LXA4 had a favorable inhibitory effect on PMMA-induced inflammation in a macrophage and OB co-culture system.
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DOI：
10.1084/jem.20080767
发表时间：
2008-11-24
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Chen M;Divangahi M;Gan H;Shin DS;Hong S;Lee DM;Serhan CN;Behar SM;Remold HG
通讯作者：
Remold HG
DOI：
10.1302/0301-620x.80b5.8513
发表时间：
1998-09-01
影响因子：
--
作者：
Granchi, D;Verri, E;Montanaro, L
通讯作者：
Montanaro, L
影响因子：
4.2
作者：
Horowitz, SM;Gonzales, JB
通讯作者：
Gonzales, JB
影响因子：
4.8
作者：
Levy, Bruce D.;Lukacs, Nicholas W.;Parkinson, John F.
通讯作者：
Parkinson, John F.
影响因子：
64.8
作者：
Lawrence, T;Bebien, M;Karin, M
通讯作者：
Karin, M