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首页> 外文期刊>Journal of orthopaedic research >Expression profiling reveals alternative macrophage activation and impaired osteogenesis in periprosthetic osteolysis.
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Expression profiling reveals alternative macrophage activation and impaired osteogenesis in periprosthetic osteolysis.

机译：表达谱揭示假体周围骨溶解中的替代性巨噬细胞活化和成骨受损。

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Interactions between periprosthetic cells and prosthetic wear debris have been recognized as an important event in the development of osteolysis and aseptic loosening. Although the ability of wear debris to activate pro-inflammatory macrophage signaling has been documented, the full repertoire of macrophage responses to wear particles has not been established. Here, we examined the involvement of alternative macrophage activation and defective osteogenic signaling in osteolysis. Using real-time RT-PCR analysis of periprosthetic soft tissue from osteolysis patients, we detected elevated levels of expression of alternative macrophage activation markers (CHIT1, CCL18), chemokines (IL8, MIP1 alpha) and markers of osteoclast precursor cell differentiation and multinucleation (Cathepsin K, TRAP, DC-STAMP) relative to osteoarthritis controls. The presence of cathepsin K positive multinuclear cells was confirmed by immunohistochemistry. Reduced expression levels of the osteogenic signaling components BMP4 and FGF18 were detected. Expression levels of TNF-alpha, IL-6, and RANKL were unchanged, while the anti-osteoclastogenic cytokine OPG was reduced in osteolysis patients, resulting in elevated RANKL:OPG ratios. In vitro studies confirmed the role of particulate debris in alternative macrophage activation and inhibition of osteogenic signaling. Taken together, these results suggest involvement in osteolysis of alternative macrophage activation, accompanied by elevated levels of various chemokines. Increased recruitment and maturation of osteoclast precursors is also observed, as is reduced osteogenesis. These findings provide new insights into the molecular pathogenesis of osteolysis, and identify new potential candidate markers for disease progression and therapeutic targeting.
机译：假体周围细胞与假体磨损碎片之间的相互作用已被认为是发生骨溶解和无菌性松动的重要事件。尽管已记录了磨损碎片激活促炎性巨噬细胞信号转导的能力，但尚未建立完整的巨噬细胞对磨损颗粒反应的库。在这里，我们检查了溶骨中替代性巨噬细胞激活和成骨信号缺陷的参与。使用实时RT-PCR分析来自骨溶解患者的假体周围软组织，我们检测到了其他巨噬细胞活化标志物（CHIT1，CCL18），趋化因子（IL8，MIP1 alpha）和破骨细胞前体细胞分化和多核化标志物的表达水平升高（组织蛋白酶K，TRAP，DC-STAMP）相对于骨关节炎对照。通过免疫组织化学证实组织蛋白酶K阳性多核细胞的存在。检测到成骨信号成分BMP4和FGF18的表达水平降低。溶骨患者的TNF-α，IL-6和RANKL的表达水平未改变，而抗破骨细胞因子OPG降低，导致RANKL：OPG比率升高。体外研究证实了颗粒碎片在替代性巨噬细胞激活和成骨信号传导抑制中的作用。综上所述，这些结果表明参与了替代性巨噬细胞活化的骨溶解，伴随着各种趋化因子水平的升高。还观察到破骨细胞前体的募集和成熟增加，成骨作用减少。这些发现为骨溶解的分子发病机理提供了新的见解，并确定了疾病进展和治疗靶向的新的潜在候选标记。

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