Health Management Center, The Affiliated Hospital (TCM) of Southwest Medical University, Luzhou 646000, Sichuan, China.
Department of Orthopedics, Yongchuan Hospital Affiliated to Chongqing Medical University, Chongqing 402160, China.
Biomed Res Int. 2018 Oct 22;2018:3928915. doi: 10.1155/2018/3928915. eCollection 2018.
UHMWPE granule could induce macrophages and inflammatory responses in interfacial tissues, which eliminated the wear debris of UHMWPE component and further induced dissolution of the surrounding bone, leading aseptic loosening. However, the mechanism of synovial cells, especially fibroblast-like synovial (FLS) cells response to UHMWPE, remains unknown. Herein we choose FLS cells as research object. Vimentin (+) CD68 (-) was identified by flow cytometry and immunofluorescent staining assay, and the cells were identified as FLS cells, which was consistent with the experimental requirements. The inhibitory evaluation showed that UHMWPE could significantly promote the proliferation and inhibit apoptosis of FLS cells in dose- and time-dependent manners and increase the levels of proinflammatory cytokines, including IL-6, IL-1, TNF-, PGE2, MMP2, and LOX. UHMWPE also can induce the expression of mIL-6R protein in FLS cells and further investigate the relationship between apoptosis and inflammation. Interestingly enough, when we added the interleukin-6 receptor antagonist (IL-6RA), the expression levels of proapoptosis-related proteins increased; in other words, UHMWPE-induced antiapoptosis diminished by IL-6RA (50 g/ml). Taken together, these findings clearly demonstrated that UHMWPE promote growth in FLS cells through upregulating inflammatory factors to produce antiapoptotic effect.
超高分子量聚乙烯颗粒会在界面组织中诱导巨噬细胞和炎症反应，这会清除超高分子量聚乙烯部件的磨损碎片，并进一步导致周围骨骼溶解，从而导致无菌性松动。然而，滑膜细胞（尤其是成纤维样滑膜细胞，FLS）对超高分子量聚乙烯的反应机制仍不清楚。在此，我们选择 FLS 细胞作为研究对象。通过流式细胞术和免疫荧光染色实验鉴定出细胞为 FLS 细胞，这与实验要求一致。抑制评估表明，超高分子量聚乙烯可显著促进 FLS 细胞的增殖，抑制其凋亡，并呈剂量和时间依赖性，同时增加促炎细胞因子（如 IL-6、IL-1、TNF-α、PGE2、MMP2 和 LOX）的水平。超高分子量聚乙烯还可以诱导 FLS 细胞中 mIL-6R 蛋白的表达，并进一步研究凋亡和炎症之间的关系。有趣的是，当我们添加白细胞介素-6 受体拮抗剂（IL-6RA）时，促凋亡相关蛋白的表达水平增加；换句话说，IL-6RA（50μg/ml）减少了超高分子量聚乙烯诱导的抗凋亡作用。总之，这些发现清楚地表明，超高分子量聚乙烯通过上调炎症因子促进 FLS 细胞生长，从而产生抗凋亡作用。
