Expression of inflammatory cytokines, RANKL and OPG induced by titanium, cobalt-chromium and polyethylene particles

Masui, Tetsuo; Sakano, Shinji; Hasegawa, Yukiharu; Warashina, Hideki; Ishiguro, Naoki

doi:10.1016/j.biomaterials.2004.05.017

Cited by 67 publications

(66 citation statements)

References 36 publications

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“…These findings are consistent with many previous studies which demonstrate similar results regarding the secretion of OPG [36,37], but differ from some observations in which there was a marked reduction of OPG secretion after particle stimulation [38]. Different compositions and physical characteristics of particles may account for these differences because these factors can affect secretions of cytokines related to inflammatory osteolysis and therefore secretion profiles [39,40]. High levels of OPG expression could reduce the pro-osteoclastic effects of RANKL, and it seems that Bzb provided no protective effects for the secretion of OPG.…”

Section: Discussionsupporting

confidence: 92%

Protection Against Titanium Particle-Induced Inflammatory Osteolysis by the Proteasome Inhibitor Bortezomib In Vivo

et al. 2012

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Wear particle-induced vascularized granulomatous inflammation and subsequent inflammatory osteolysis is the most common cause of aseptic loosening after total joint replacement (TJR); however, the precise mechanism by which this occurs is unclear. This study investigates the effects of the proteasome inhibitor bortezomib (Bzb) on the expression of key biochemical markers of bone metabolism and vascularised granulomatous tissues, such as receptor activator of nuclear factor-κB ligand (RANKL), osteoprotegerin (OPG), vascular endothelial growth factor (VEGF) and tumor necrosis factor receptor-associated factor 6 (TRAF6). In addition, the effect of Bzb on apoptosis of CD68+ cells was examined. A total of 32 female BALB/C mice were randomly divided into four groups. After implantation of calvaria bone from syngeneic littermates, titanium (Ti) particles were injected into established air pouches for all mice (excluding negative controls) to provoke inflammatory osteolysis. Subsequently, Bzb was administered at a ratio of 0, 0.1, or 0.5 mg/kg on day 1, 4, 8, and 11 post-surgery to alleviate this response. All of the air pouches were harvested 14 days after the surgical procedure and were processed for molecular and histological analysis. The results demonstrated that Ti injection elevated the expression of RANKL, OPG, VEGF, and TRAF6 at both the gene and protein levels, increased counts of infiltrated cells and thickness of air pouch membranes, and elevated the apoptosis index (AI) of CD68+ cells. Bzb treatment significantly improved Ti particle-induced implanted bone osteolysis, attenuated vascularised granulomatous tissues and elevated AI of CD68+ cells. Therefore, the proteasome pathway may represent an effective therapeutic target for the prevention and treatment of aseptic loosening.

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Section: Discussionsupporting

confidence: 92%

Protection Against Titanium Particle-Induced Inflammatory Osteolysis by the Proteasome Inhibitor Bortezomib In Vivo

et al. 2012

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“…compared to controls there was no change in genes defining the RANKL/OPG pathway. One possible explanation is based on the fact that osteoclastogenesis can be induced by the actions of inflammatory cytokines, working synergistically with the RANKL/ RANK pathway [Masui et al, 2005]. In particular, TNFa in the presence of M-CSF can stimulate osteoclast differentiation in vitro, but need IL-1 for full potency [Sabokbar et al, 2003].…”

Section: Discussionmentioning

confidence: 99%

Fluid pressure induces osteoclast differentiation comparably to titanium particles but through a molecular pathway only partly involving TNFα

Nilsson¹,

Norgård²,

Andersson³

et al. 2012

J of Cellular Biochemistry

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In contrast to the well-understood inflammatory pathway driven by TNFα, by which implant-derived particles induce bone resorption, little is known about the process in which loosening is generated as a result of force-induced mechanical stimulus at the bone-implant interface. Specifically, there is no knowledge as to what cells or signaling pathways couple mechanical stimuli to bone resorption in context of loosening. We hypothesized that different stimuli, i.e., fluid flow versus wear particles, act through different cytokine networks for activation and localization of osteoclasts. By using an animal model in which osteoclasts and bone resorption were induced by fluid pressure or particles, we were able to detect distinct differences in osteoclast localization and inflammatory gene expression between fluid pressure and titanium particles. Fluid pressure recruits and activates osteoclasts with bone marrow contact away from the fluid pressure exposure zone, whereas titanium particles recruit and activate osteoclasts in areas in direct contact to particles. Fluid pressure induced weaker expression of the selected inflammatory related genes, although the eventual degree of osteoclast induction was similar in both models. Using TNFαRa (4 mg/kg) (Enbrel) and dexamethasone (2 mg/kg) as specific and more general suppressors of inflammation we showed that the TNFαRa failed to generate statistically impaired osteoclast generation while dexamethasone was much more potent. These results demonstrate that fluid pressure induces osteoclasts at a different localization than titanium particles by a molecular pathway less associated with TNFα and the innate system, which open up for other pathways controlling pressure induced osteoclastogenesis.

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“…It appears to play an important role in both immune responses and bone morphogenesis [24,25]. The ratio of the expression of RANKL to OPG is critical to the outcome of bone resorption [26]. Kim et al [27] demonstrated decreased levels of OPG in failed THA.…”

Section: Discussionmentioning

confidence: 99%

Multiple biomarkers analysis for the early detection of prosthetic aseptic loosening of hip arthroplasty

Huang

et al. 2013

International Orthopaedics (SICOT)

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Expression of inflammatory cytokines, RANKL and OPG induced by titanium, cobalt-chromium and polyethylene particles

Cited by 67 publications

References 36 publications

Protection Against Titanium Particle-Induced Inflammatory Osteolysis by the Proteasome Inhibitor Bortezomib In Vivo

Protection Against Titanium Particle-Induced Inflammatory Osteolysis by the Proteasome Inhibitor Bortezomib In Vivo

Fluid pressure induces osteoclast differentiation comparably to titanium particles but through a molecular pathway only partly involving TNFα

Multiple biomarkers analysis for the early detection of prosthetic aseptic loosening of hip arthroplasty

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