Osteoclasts lose innate inflammatory reactivity to metal and polymer implant debris compared to monocytes/macrophages.
Osteoclasts lose innate inflammatory reactivity to metal and polymer implant debris compared to monocytes/macrophages.
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DOI：
10.2174/1874325001307010605
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发表时间：
2013
期刊：
影响因子：
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通讯作者：
Hallab NJ
中科院分区：
文献类型：
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作者：
Yadav J;Samelko L;Gilvar P;McAllister K;Hallab NJ
关节置换术的长期无菌性失败通常归因于植入物碎片诱导的炎症和骨质溶解。这种反应主要由免疫细胞和骨细胞（分别为单核细胞/巨噬细胞和破骨细胞）介导，在存在植入物碎片（例如金属颗粒和离子）的情况下，释放促炎细胞因子，如IL-1β、TNF-α和IL-6。植入物碎片引发破骨细胞与单核细胞/巨噬细胞炎症反应的相对程度尚不清楚，即破骨细胞是否是植入物碎片抗炎治疗的可行靶点？我们从危险信号（IL-1β）和病原体识别（TNF-α）反应性的角度，使用植入物碎片进行并行比较，研究了相对单核细胞与破骨细胞的炎症反应（激发剂：钴合金、钛合金和PMMA颗粒，直径为0.9- 1.8 μ m的ECD和钴，以及镍离子0.01- 0.1 mM，均使用和不使用LPS预充）。与破骨细胞样细胞相比，人单核细胞/巨噬细胞与植入物碎片反应，产生的细胞因子多100倍。钴合金颗粒刺激诱导单核细胞产生>1000 pg/ml的IL-1β和TNF-α，破骨细胞产生<50 pg/mL的IL-1β和TNF-α。钴离子在单核细胞/巨噬细胞中诱导> 3000 pg/mL的IL-1β和TNF-α，在破骨细胞中诱导<50 pg/mL的IL-1β和TNF-α。碎片处理的单核细胞/巨噬细胞上清液的旁分泌作用能够诱导比直接碎片攻击破骨细胞更大的破骨细胞生成（TRAP+，p<0.06）和炎症。我们的研究结果表明，随着单核细胞/巨噬细胞分化成破骨细胞，它们在很大程度上失去了对植入物碎片的先天免疫反应性，因此可能不像单核细胞/巨噬细胞那样是减轻碎片诱导的炎症的相关治疗靶点。
Long-term aseptic failures of joint replacements are generally attributed to implant debris-induced inflammation and osteolysis. This response is largely mediated by immune and bone cells (monocytes/macrophages and osteoclasts, respectively), that in the presence of implant debris (e.g. metal particles and ions), release pro-inflammatory cytokines such as IL-1β, TNF-α, and IL-6. The relative degree to which implant debris can illicit inflammatory response(s) from osteoclasts vs monocytes/macrophages is unknown, i.e. are osteoclasts a viable target for anti-inflammatory therapy for implant debris? We investigated relative monocyte versus osteoclast inflammatory responses in a side-by-side comparison using implant debris from the perspective of both danger signaling (IL-1β) and pathogenic recognition (TNF-α) reactivity (Challenge Agents: Cobalt-alloy, Titanium-alloy, and PMMA particles, 0.9-1.8um-dia ECD and Cobalt, and Nickel-ions 0.01-0.1mM, all with and without LPS priming). Human monocytes/macrophages reacted to implant debris with >100 fold greater production of cytokines compared to osteoclast-like cells. Particulate Co-alloy challenge induced >1000 pg/ml of IL-1β and TNF-α, in monocytes and <50pg/mL IL-1β and TNF-α in osteoclasts. Cobalt ions induced >3000pg/mL IL-1β and TNF-α in monocytes/macrophages and <50pg/mL IL-1β and TNF-α in osteoclasts. The paracrine effect of supernatants from debris-treated monocytes/macrophages was capable of inducing greater osteoclastogenesis (TRAP+, p<0.06) and inflammation than direct debris challenge on osteoclasts. Our results indicate that as monocytes/macrophages differentiate into osteoclasts, they largely lose their innate immune reactivity to implant debris and thus may not be as relevant a therapeutic target as monocytes/macrophages for mitigating debris-induced inflammation.