Co–Cr–Mo alloy particles induce tumor necrosis factor alpha production in MLO-Y4 osteocytes: A role for osteocytes in particle-induced inflammation

Abstract

Wear debris-induced osteolysis is purportedly the limiting problem affecting the long term results of joint arthroplasty. Pathogenic effects of wear debris in peri-implant cells such as macrophages, osteoblasts and osteoclasts have been well studied. In contrast, the affects of wear-debris on osteocytes, which make up over 90% of all bone cells, remains unknown. We hypothesized that metal implant debris can induce the proinflammatory response in osteocytes. This study demonstrated the effects of cobalt-chromium-molybdenum alloy (Co-Cr-Mo) particles on a well-characterized MLO-Y4 osteocyte cell line. Co-Cr-Mo alloy particle treatment significantly (p<0.05) up-regulated tumor necrosis factor alpha (TNFα) gene expression after 3 and 6 hr and TNFα protein production after 24 hr, but down-regulated interleukin-6 (IL-6) gene expression after 6 hr. Co-Cr-Mo alloy particle treatment also induced osteocyte apoptosis after 24 hr. This apoptotic effect was partially (40%) dependent on TNFα. Therefore, our results suggest that osteocytes play a role in particle induced inflammation and bone resorption following total hip arthroplasty by inducing pro-inflammatory cytokines and inducing osteocyte apoptosis.

Comparison of the cytotoxic and inflammatory responses of titanium particles with different methods for endotoxin removal in RAW264.7 macrophages

“…In fact, some papers contain no specific methods for the removal of endotoxins from particles. Instead, these studies describe the use of 0.1 lm polycarbonate filter membranes [11][12][13], ethanol [14][15][16][17], autoclaving [14], UV light [14], gamma irradiation [18,19] or sterilization without including detailed descriptions [20,21]. However, these methods do not remove most of the endotoxins from particles.…”

In vitroassessment of molybdenum-induced secretory activity, proliferation and apoptosis of porcine ovarian granulosa cells

“…The data suggested that venous and capillary endothelial proliferation are important targets in ATM therapy, but that other vascular segments and tumor cells may be less influenced. Kanaji et al [45] also examined the effects of cobalt-chromium-molybdenum alloy (Co-Cr-Mo) particles on a well-characterized MLO-Y4 osteocyte cell line. The Co-Cr-Mo alloy particle treatment was found to induce osteocyte apoptosis after 24 h. The ratio of apoptotic cells were 29%, 35%, and 57% with Downloaded by [University of Nebraska, Lincoln] at 16: 22 12 April 2015 treatment of PM-8 after 24, 48, and 72 h, respectively, which suggested that the anti-tumor activity of PM-8 results from the activation of the apoptotic pathway.…”

In vitro cytocompatibility evaluation of hydrogenated and unhydrogenated carbon films

“…Since a-C film and a-C:H film show different tribology properties due to the different microstructure and surface properties [16,31,32], differences in cytocompatibility of a-C and a-C:H film should also be considered. What's more, because wear debris of artificial joint may cause osteolysis, aseptic loosening and eventually lead to prosthesis failure [4,6,7], the cytotoxicity of DLC debris is also worth for research [33]. As we all know, DLC film is hard and has excellent wear resistance, so it is difficult to collect wear debris for in vitro evaluation.…”

“…Such good wear resistant makes MOM a promising friction pair. However, CoCr debris and metal ions such as Co 2+ and Cr 3+ can be generated due to the wear and corrosion process, which would induce pro-inflammatory response, cytotoxicity to osteoblasts and even DNA damage [3][4][5]. As a result, there is serious risk of aseptic loosening and genotoxicity with this type of implant, and this restricts the application of MOM in artificial arthroplasty [6].…”