The effect of TNF-? on osteoblasts in metal wear-induced periprosthetic bone loss

Abstract

Aims This study aimed to examine the effects of tumour necrosis factor-alpha (TNF-?) on osteoblasts in metal wear-induced bone loss. Methods TNF-? immunoexpression was examined in periprosthetic tissues of patients with failed metal-on-metal hip arthroplasties and also in myeloid MM6 cells after treatment with cobalt ions. Viability and function of human osteoblast-like SaOs-2 cells treated with recombinant TNF-? were studied by immunofluorescence, terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) assay, western blotting, and enzyme-linked immunosorbent assay (ELISA). Results Macrophages, lymphocytes, and endothelial cells displayed strong TNF-? immunoexpression in periprosthetic tissues containing metal wear debris. Colocalization of TNF-? with the macrophage marker CD68 and the pan-T cell marker CD3 confirmed TNF-? expression in these cells. Cobalt-treated MM6 cells secreted more TNF-? than control cells, reflecting the role of metal wear products in activating the TNF-? pathway in the myeloid cells. While TNF-? did not alter the immunoexpression of the TNF-receptor 1 (TNF-R1) in SaOs-2 cells, it increased the release of the soluble TNF-receptor 1 (sTNF-R1). There was also evidence for TNF-?-induced apoptosis. TNF-? further elicited the expression of the endoplasmic reticulum stress markers inositol-requiring enzyme (IRE)-1?, binding-immunoglobulin protein (BiP), and endoplasmic oxidoreductin1 (Ero1)-L?. In addition, TNF-? decreased pro-collagen I ? 1 secretion without diminishing its synthesis. TNF-? also induced an inflammatory response in SaOs-2 cells, as evidenced by the release of reactive oxygen and nitrogen species and the proinflammatory cytokine vascular endothelial growth factor. Conclusion The results suggest a novel osteoblastic mechanism, which could be mediated by TNF-? and may be involved in metal wear debris-induced periprosthetic bone loss. © 2020 Author(s) et al. This is an open-access article distributed under the terms ofthe Creative Commons Attribution Non-Commercial No Derivatives (CC BY-NC-ND 4.0) licence, which permits the copying and redistribution of the work only, and providedthe original author and source are credited. See https://creativecommons.org/licenses/by-nc-nd/4.0/.