Gene expression analysis of osteoblastic cells contacted by orthopedic implant particles

Pioletti, Dominique P.; Leoni, Lorenzo M.; Genini, Davide; Takei, Hiroshi; Du, Pinyi; Corbeil, Jacques

doi:10.1002/jbm.10218

Cited by 58 publications

(47 citation statements)

References 33 publications

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“…[56][57][58] To address whether this may be true in vivo, we performed expression analysis on two key regulators of osteogenesis, BMP4 and FGF18. FGF18 has been reported to promote osteogenesis and osteoblast differentiation.…”

Section: Discussionmentioning

confidence: 99%

Expression profiling reveals alternative macrophage activation and impaired osteogenesis in periprosthetic osteolysis

Koulouvaris

Ivashkiv

et al. 2007

Journal Orthopaedic Research

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Interactions between periprosthetic cells and prosthetic wear debris have been recognized as an important event in the development of osteolysis and aseptic loosening. Although the ability of wear debris to activate pro-inflammatory macrophage signaling has been documented, the full repertoire of macrophage responses to wear particles has not been established. Here, we examined the involvement of alternative macrophage activation and defective osteogenic signaling in osteolysis. Using real-time RT-PCR analysis of periprosthetic soft tissue from osteolysis patients, we detected elevated levels of expression of alternative macrophage activation markers (CHIT1, CCL18), chemokines (IL8, MIP1 a) and markers of osteoclast precursor cell differentiation and multinucleation (Cathepsin K, TRAP, DC-STAMP) relative to osteoarthritis controls. The presence of cathepsin K positive multinuclear cells was confirmed by immunohistochemistry. Reduced expression levels of the osteogenic signaling components BMP4 and FGF18 were detected. Expression levels of TNF-a, IL-6, and RANKL were unchanged, while the anti-osteoclastogenic cytokine OPG was reduced in osteolysis patients, resulting in elevated RANKL:OPG ratios. In vitro studies confirmed the role of particulate debris in alternative macrophage activation and inhibition of osteogenic signaling. Taken together, these results suggest involvement in osteolysis of alternative macrophage activation, accompanied by elevated levels of various chemokines. Increased recruitment and maturation of osteoclast precursors is also observed, as is reduced osteogenesis. These findings provide new insights into the molecular pathogenesis of osteolysis, and identify new potential candidate markers for disease progression and therapeutic targeting. ß

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Section: Discussionmentioning

confidence: 99%

Expression profiling reveals alternative macrophage activation and impaired osteogenesis in periprosthetic osteolysis

Koulouvaris

Ivashkiv

et al. 2007

Journal Orthopaedic Research

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“…In order to have a comprehensive description of the cell-implant interaction with surface treated Ti alloy, cDNA microarray technology may be performed e.g. [34,35]. This represents the next step of this study.…”

Section: Discussionmentioning

confidence: 99%

Effect of different Ti–6Al–4V surface treatments on osteoblasts behaviour

Ku¹,

et al. 2002

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The purpose of the present work was to examine the effect of different Ti-6Al-4V surface treatments on osteoblasts behaviour. Previous work in this laboratory has demonstrated that an ageing treatment reduces metal ion release from this alloy compared to standard passivation procedures. In this study, human osteosarcoma MG-63 were used in short-term in vitro tests to assay for cell viability and cell proliferation at 12, 24 and 72 h while SaOS-2 were used in long-term in vitro tests to assay for osteonectin, osteopontin, osteocalcin gene expression, total protein amount (TP), alkaline phosphatase activity (ALP) and fibronectin production (FN) for 1-4 weeks. Epifluorescence microscopy was used to observe SaOS-2 cell morphology. After 24 h, there was no difference in MG-63 cell viability/proliferation or in SaOS-2 cell morphology between the different surface treatments. For the longterm tests, the aged Ti-6Al-4V induced significantly higher cell proliferation than the control Ti-6Al-4V at 72 h. At week 1, no difference in the osteonectin, osteopontin, and osteocalcin gene expression was found between samples. The peak of ALP activity appeared earlier at week 2 for the control surface compared with the passivated and aged surfaces. The early increase in ALP activity for the control sample could be a compensatory effect of decreased osteoblasts proliferation. There was no difference in the expression of FN for the different surface treatments. Our present results showed that the different surface treatments, which induced different metal ion release kinetics and surface properties, influenced the cell proliferation and ALP activity of osteoblast cells. Aluminium ions release kinetics as well as presence of vanadium ions may play a major role in influencing the osteoblasts behaviour in the present study. r

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“…Moreover, combination of particles and cytokines had a synergic effect on the production of inflammatory factors [13]. Using microarray techniques, it has been shown that particles had a profound impact on genes coding for inflammatory cytokines and genes controlling the nuclear architecture [14]. Nevertheless, little information is available regarding the effect of particles on osteoclastogenetic factors produced by osteoblasts.…”

Section: Introductionmentioning

confidence: 99%

The influence of wear particles in the expression of osteoclastogenesis factors by osteoblasts

Pioletti

Kottelat

2004

Biomaterials

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Orthopedic implant failures are often associated with peri-implant osteolysis. Particles generated from the wear process have been suspected to play an important role in this situation. Indeed, the peri-implant osteolysis could be due to the presence of particles stimulating the osteoclastogenesis process. We hypothesize then that the presence of a low particle concentration positively influences osteoblasts to produce osteoclastogenesis factors. If true, this hypothesis would then support the idea that the particles could be at the origin of the process leading to implant loosening. To check the validity of this hypothesis, we quantified in vitro the production of different genes involved in the osteoclastogenesis process using primary isolated human osteoblasts treated or not with particles. Results showed that low concentrations of particles might have a stimulating effect on osteoblasts to produce osteoclastogenesis factors as demonstrated by the increase of RANKL and CSF-1 gene expression in the particle group. r

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Gene expression analysis of osteoblastic cells contacted by orthopedic implant particles

Cited by 58 publications

References 33 publications

Expression profiling reveals alternative macrophage activation and impaired osteogenesis in periprosthetic osteolysis

Expression profiling reveals alternative macrophage activation and impaired osteogenesis in periprosthetic osteolysis

Effect of different Ti–6Al–4V surface treatments on osteoblasts behaviour

The influence of wear particles in the expression of osteoclastogenesis factors by osteoblasts

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