Impaired Autophagy in the Fibroblasts by Titanium Particles Increased the Release of CX3CL1 and Promoted the Chemotactic Migration of Monocytes
Impaired Autophagy in the Fibroblasts by Titanium Particles Increased the Release of CX3CL1 and Promoted the Chemotactic Migration of Monocytes
复制标题
钛颗粒损伤成纤维细胞自噬增加CX3CL1释放并促进单核细胞趋化迁移
DOI：
10.1007/s10753-019-01149-0
复制
发表时间：
2020-04-01
期刊：
影响因子：
5.1
通讯作者：
Hao，Yong-Qiang
中科院分区：
文献类型：
--
作者：
Wu，Wen;Wang，Lei;Hao，Yong-Qiang
无菌性松动（AL）是全髋关节置换术（THA）失败的最常见原因。假体磨损颗粒诱导的单核细胞聚集到假体周围组织和随后的炎症反应被认为是AL的主要贡献。成纤维细胞是界面膜（IFM）的主要细胞类型，IFM是失败的tha假体周围骨溶解的主要病理特征。考虑到成纤维细胞作为前哨细胞在趋化因子合成和炎症调节中的作用，我们假设成纤维细胞可能参与了假体周围骨溶解与颗粒碎片相关的单核细胞募集发病机制。本研究探讨了成纤维细胞对单核细胞募集的诱导作用。结果表明，从松散THAs的ifm中分离的钛（Ti）颗粒刺激的成纤维细胞通过增加CX3CL1 （C-X3-C基序趋化因子配体1）的释放，显著促进THP-1细胞的趋化迁移。进一步的研究表明，Ti颗粒刺激通过损害成纤维细胞的自噬而增加ADAM10 （ADAM金属肽酶结构域10）的表达，进而增加CX3CL1的切割和脱落。因此，我们对无菌性松动的发病机制提出了新的见解，这意味着成纤维细胞中的自噬- adam10 - cx3cl1信号通路可以被利用来减轻无菌性松动中单核细胞募集引起的炎症，并改善关节装置的关节性能。
Aseptic loosening (AL) is the most frequent cause of failure of total hip arthroplasties (THA). Prosthetic wear particle-induced monocyte recruitment to the periprosthetic tissue and subsequent inflammatory response are thought to be the major contribution to AL. Fibroblast is a dominant cell type in interfacial membrane (IFM) which is the main pathological feature of periprosthetic osteolysis in failed THAs. Considering the role of fibroblasts, as sentinel cells, in the synthesis of chemokines and regulation of inflammation, we hypothesize that fibroblasts might be involved in the monocyte recruitment in the pathogenesis of periprosthetic osteolysis associated with particle debris. This study explored the induction of fibroblasts on the monocyte recruitment. The results showed that titanium (Ti) particle-stimulated fibroblasts isolated from IFMs of loosened THAs significantly promoted the chemotactic migration of THP-1 cells by increasing the release of CX3CL1 (C-X3-C motif chemokine ligand 1). Further investigation demonstrated that Ti particle stimulation increased the expression of ADAM10 (ADAM metallopeptidase domain 10) by impairing autophagy in the fibroblasts and in turn increased the cleavage and shedding of CX3CL1. Thus, we propose a new insight to the pathogenesis of aseptic loosening which implies that autophagy-ADAM10-CX3CL1 signaling pathway in fibroblasts can be leveraged to alleviating inflammation caused by monocyte recruitment in aseptic loosening and improving performance of articulation of the joint device.