髋关节假体周围骨质溶解的生物学机制

摘要

Periprosthetic osteolysis and aseptic loosening after total hip arthroplasty are the common causes for revision surgery,which are initiated by wear particles released from the articular surfaces of prosthetic components.These components include ultra-high molecular weight polyethylene,titanium alloy,Al2O3,ZrO2 and polymethylmethacrylate.Wear particles activate macrophage via phagocytosis or pattern recognition receptor,resulting in release of inflammatory mediators such as macrophage colony-stimulating factor (M-CSF),macrophage chemotactic protein-1 (MCP-1),macrophage inhibitory protein-1 (MIP-1),IL-1β,IL-6 and TNF-α.Furthermore,wear particles stimulate M0 macrophage to polarize to M1 macrophage,promoting the release of inflammatory mediators.The periprosthetic osteolysis process is a cell/cytokine-mediated biological cascade induced by macrophage activation,involving the monocyte/macrophage cell line,such as macrophages,osteoclasts,and dendritic cells.The mesenchymal cells,including osteoblasts,osteocytes,fibroblasts and lymphocytes,lead to a deviation in the balance of osteoblast-osteoclast interactions within the basic multicellular unit,resulting in periprosthetic osteolysis.Fibrobalst,dendritic,and lymphocyte cells can enhance the recruitment and activation of macrophages by secreting MCP-1,MIP-1,and IL-8.Furthermore,the upregulated expression of RANKL,TNF-α,and IL-1 β facilitates the osteoclast differentiation from osteoclast precursor.TNF-α,IL-1 β together with wear particles can upregulate the expression of IL-6,MCP-1 and M-CSF of osteoblast and promote the recruitment and activation of macrophages.Nuclear transcriptional factor NF-κB plays a vital role in mediating periprosthetic inflammatory response and gene expression of bone metabolism.Different inflammatory factors can induce different expression of its downstream gene,ultimately,promoting or hindering the osteolysis process.The individual difference of periprosthetic osteolysis may also relate to single nucleotide polymorphism of IL-1RA,IL-6 and MMP-1 gene.%髋关节置换术后假体磨损产生微粒引起的假体周围骨质溶解和假体松动,导致手术失败,往往需要接受翻修手术.关节假体的任一组成材料(超高分子聚乙烯、钛合金、A1203、ZrO2、聚甲基丙烯酸甲酯等)产生的磨损微粒都会引起骨质溶解.磨损微粒通过吞噬作用或模式识别受体作用于巨噬细胞引起趋化因子巨噬细胞集落刺激因子(macrophage colony-stimulating factor,M-CSF)、巨噬细胞趋化蛋白(macrophage chemotactic protein-1,MCP-1)、巨噬细胞炎性蛋白(macrophage inhibitory protein-1,MIP-1)和促炎因子白细胞介素(interleukin,IL)-1β、IL-6、肿瘤坏死因子-α(tumor necrosis factorα,TNF-α)等炎性介质释放,启动骨质溶解的进程.此外磨损微粒还会促使M0型巨噬细胞极化为M1型而促进炎症因子释放.骨质溶解过程中单核巨噬细胞系来源的巨噬细胞、破骨细胞、树突状细胞,骨髓间质来源的成骨细胞、骨细胞、成纤维细胞,以及淋巴细胞通过细胞因子相互作用,最终使假体周围基础多细胞单位(bone multicellular units,BMU)中的破骨活动强于成骨活动,导致骨质溶解发生.成纤维细胞、树突细胞和和淋巴细胞分泌MCP-1、MIP-1、IL-8可促进局部巨噬细胞的募集和激活,另外RANKL、TNF-α和IL-1p表达增多可促进破骨细胞前体细胞分化为成熟破骨细胞.TNF-α和IL-1β与磨损微粒作用于成骨细胞可促进IL-6、MCP-1和M-CSF表达,同时也促进巨噬细胞的募集和激活.核内转录因子NF-κB在调节假体周围炎症反应和骨代谢基因表达中有重要作用,不同炎性因子的作用下NF-κB下游基因表达不同,从而起到促进或对抗骨质溶解的作用.此外,假体周围骨质溶解的个体差异性可能还与IL-1RA基因、IL-6基因、基质金属蛋白酶-1(matrix metalloproteinase-1,MMP-1)基因的单核苷酸多态性有关.