Spinal microglial activation in a murine surgical model of knee osteoarthritis.
Spinal microglial activation in a murine surgical model of knee osteoarthritis.
复制标题
膝骨关节炎小鼠手术模型中的脊髓小胶质细胞激活。
DOI：
10.1016/j.joca.2016.09.007
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发表时间：
2017
影响因子：
7
通讯作者：
Malfait,AM
中科院分区：
文献类型：
--
作者：
Tran,PB;Miller,RE;Ishihara,S;Miller,RJ;Malfait,AM
小胶质细胞增生，即小胶质细胞的激活，被认为有助于背角中的突触传递，从而促进慢性疼痛。本研究的主要目的是记录野生型（WT）和Adamts 5基因敲除小鼠内侧半月板（DMM）失稳后背角小胶质细胞增生的时间分布。由于神经元fractalkine（CX 3CL 1）有助于小胶质细胞增生，我们评估了DMM后其从背根神经节（DRG）培养物中的释放。在10周龄雄性WT、CX 3CR 1-绿色荧光蛋白（GFP）或Adamts 5缺失C57 BL/6小鼠的右膝中进行设计DMM或假手术。使用von Frey纤维监测后爪机械异常性疼痛。根据Iba 1免疫反应性小胶质细胞的形态学，在术后4、8和16周评估L4背角小胶质细胞增生。培养DRG细胞（L3-L5），收集上清液进行Fractalkine（FKN）ELISA. ResultsWT小鼠，DMM后第8周和第16周激活的小胶质细胞数量增加，但4周后没有增加，而不是假手术。DRG培养显示在第8周和第16周基础FKN的释放增加，Adamts 5基因敲除小鼠在DMM后16周内没有发生机械性异常性疼痛。因此，这些小鼠的背根节培养物没有表现出FKN释放增加，也没有发生背角小胶质细胞增生。结论DMM手术导致晚期背角小胶质细胞增生。与DRG FKN释放的时间相关性表明它可能有助于小胶质细胞增生。Adamts 5基因敲除小鼠的小胶质细胞增生减少，这表明小胶质细胞增生与关节损伤和伴随的持续性疼痛有关，这些小鼠在DMM后受到保护，免受关节损伤和相关的机械性异常性疼痛。
ObjectiveMicrogliosis, the activation of microglial cells, is thought to contribute to synaptic transmission in the dorsal horn and thereby promote chronic pain. The primary aim of this study was to document the temporal profile of dorsal horn microgliosis after destabilization of the medial meniscus (DMM) in wild type (WT) andAdamts5null mice. Since neuronal fractalkine (CX3CL1) contributes to microgliosis, we assessed its release from dorsal root ganglia (DRG) cultures after DMM.DesignDMM or sham surgery was performed in the right knee of 10-week old male WT, CX3CR1-green fluorescent protein (GFP), orAdamts5null C57BL/6 mice. Hind paw mechanical allodynia was monitored using von Frey fibers. L4 dorsal horn microgliosis was assessed 4, 8 and 16 weeks after surgery, based on the morphology of Iba1-immunoreactive microglia. DRG cells (L3–L5) were cultured and supernatants collected for fractalkine (FKN) ELISA.ResultsIn WT mice, numbers of activated microglia were increased 8 and 16 weeks, but not 4 weeks, after DMM but not sham surgery. DRG cultures showed increased basal FKN release at 8 and 16 weeks.Adamts5null mice did not develop mechanical allodynia up to 16 weeks after DMM. Accordingly, DRG cultures from these mice did not exhibit increased FKN release and dorsal horn microgliosis did not occur.ConclusionDMM surgery leads to late stage dorsal horn microgliosis. The temporal correlation with DRG FKN release suggests it may contribute to microgliosis. Reduced microgliosis inAdamts5null mice, which are protected from joint damage and associated mechanical allodynia after DMM, suggests that microgliosis is associated with joint damage and accompanying persistent pain.