Factors regulating osteoclast formation in human tissues adjacent to peri-implant bone loss: expression of receptor activator NFκB, RANK ligand and osteoprotegerin

Crotti, Tania; Smith, Malcolm D.; Findlay, David M.; Zreiqat, Hala; Ahern, Michael; Weedon, Helen; Hatzinikolous, G; Capone, M; Holding, C.A.; Haynes, David R.

doi:10.1016/s0142-9612(03)00556-8

Cited by 148 publications

(138 citation statements)

References 36 publications

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“…Abnormally higher levels of RANKL (mRNA and protein) were predominantly associated with cells containing wear particles, and may significantly contribute to the UHMWPE particleinduced osteoclastogenesis. 25 The data from this study illustrate that UHMWPE particles induce similar pouch tissue inflammation, and increased gene expression of RANKL, TNFa, and IL-1b in RANK À/À mice. CPK is a protease known to be a cellular marker for mature osteoclasts.…”

Section: Discussionmentioning

confidence: 56%

Implant wear induces inflammation, but not osteoclastic bone resorption, in RANK^–/– mice

Ren

Peng

et al. 2006

Journal Orthopaedic Research

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Signaling of RANK (receptor activator of nuclear factor kappa B) through its ligand RANKL appears critical in osteolysis associated with aseptic loosening (AL). The purpose of this study was to investigate the role of RANK in a murine osteolysis model developed in RANK knockout (RANK À/À ) mice. Ultra high molecular weight polyethylene (UHMWPE) debris was introduced into established air pouches on RANK À/À mice, followed by implantation of calvaria bone from syngeneic littermates. Wild type C57BL/6 (RANK þ/þ ) mice injected with either UHMWPE or saline alone were included in this study. Pouch tissues were collected 14 days after UHMWPE inoculation for molecular and histology analysis. Results showed that UHMWPE stimulation induced strong pouch tissue inflammation in RANK À/À mice, as manifested by inflammatory cellular infiltration, pouch tissue proliferation, and increased gene expression of IL-1b, TNFa, and RANKL. However, the UHMWPE-induced inflammation in RANK À/À mice was not associated with the osteoclastic bone resorption observed in RANK þ/þ mice. In RANK þ/þ mice subjected to UHMWPE stimulation, a large number of TRAP þ cells were found on the implanted bone surface, where active osteoclastic bone resorption was observed. No TRAP þ cells were found in UHMWPE-containing pouch tissues of RANK À/À mice. Consistent with the lack of osteoclastic activity shown by TRAP staining, no significant UHMWPE particle-induced bone resorption was found in RANK À/À mice. A well preserved bone collagen content (Van Gieson staining) and normal plateau surface contour [microcomputed tomography (mCT)] of implanted bone was observed in RANK À/À mice subjected to UHMWPE stimulation. In conclusion, this study provides the evidence that UHMWPE particles induce strong inflammatory responses, but not associated with osteoclastic bone resorption in RANK À/À mice. This indicates that RANK signaling is essential for UHMWPE particle-induced osteoclastic bone resorption, but does not participate in UHMWPE particle-induced inflammatory response. ß

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Section: Discussionmentioning

confidence: 56%

Implant wear induces inflammation, but not osteoclastic bone resorption, in RANK^–/– mice

Ren

Peng

et al. 2006

Journal Orthopaedic Research

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“…11 Abnormally higher levels of RANKL (mRNA and protein) were predominantly associated with cells containing wear particles, and may significantly contribute to the development of AL. 8 Using the mouse air pouch model, we have demonstrated that UHMWPE particles generated significantly higher RANK and RANKL gene expression and induced accumulation of TRAP þ cells in pouch tissues, indicating RANK/RANKL mediated osteoclastognesis is activated upon wear particles stimulation. 4 Because RANKL/RANK signaling acts as a common mediator for inflammatory osteoclastogenesis, 30 modulation of RANKL/ RANK gene expression provides a unique opportunity to design novel therapies to inhibit wear particles induced bone loss.…”

Section: Discussionmentioning

confidence: 84%

“…[4][5][6] RANKL, a membrane-bound factor expressed on the surface of stromal cells/ osteoblasts, 7 stimulates osteoclastogenesis by signaling through its membrane receptor RANK. 7,8 Both the expression and activity of RANK/RANKL mediators is, in turn, regulated by many factors, such as TNF-a and IL-1b, that have been shown to be present in the tissue adjacent to loose implants. 9,10 Recent studies have demonstrated that the RANKL expression is increased in tissues adjacent to loose prostheses in patients.…”

Section: Introductionmentioning

confidence: 99%

“…9,10 Recent studies have demonstrated that the RANKL expression is increased in tissues adjacent to loose prostheses in patients. 3,6,8,11 Using a mouse inflammation model, 12 we have demonstrated that ultrahigh molecular-weight polyethylene (UHMWPE) debris provokes tissue inflammation associated with a significant increase of RANKL gene expression. 4 In fact, blocking RANKL activity using either an antagonist RANK:Fc IgG 13 or an adeno-associated virus (AAV)-mediated OPG gene therapy 14 inhibit wear debris-stimulated osteoclast formation and bone resorption.…”

Section: Introductionmentioning

confidence: 99%

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Erythromycin inhibits wear debris‐induced inflammatory osteolysis in a murine model

Ren

Peng

et al. 2005

Journal Orthopaedic Research

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Up to 20% of patients with total joint arthroplasty will develop radiographic evidence of aseptic loosening (AL), which most likely results from an inflammatory response to billions of wear debris shed from the implant. Our previous work has demonstrated that erythromycin (EM), a macrolide antibiotic, inhibits wear debris-induced inflammatory osteoclastogenesis through the reduction of cytokine production and osteoclast differentiation, both of which involve the NF-kB pathway. The aim of the current study was to determine whether EM inhibits wear debris-induced inflammatory osteolysis in a murine osteolysis model. Ultrahigh molecular-weight polyethylene (UHMWPE) debris was introduced into established air pouches on BALB/c mice, followed by implantation of calvaria bone from syngeneic littermates. EM (2 mg/kg/day) was given to mice intraperitoneally 2 days before UHMWPE introduction and maintained until the sacrifice of the mice. Mice with and without EM treatment, as well as control mice injected with saline alone were included in this study. Pouch tissues were collected 14 days after UHMWPE inoculation for molecular and histology analysis. Our findings indicate that: (1) EM reduced UHMWPE-induced tissue inflammation, including the diminished pouch membrane thickness, reduced inflammatory cellular infiltration, and lowered IL-1b and TNF-a expression (mRNA and protein); (2) EM inhibited UHMWPE-induced osteoclastogenesis, with reduced gene activation of RANK, RANKL, and CPK, and diminished RANKL expression in UHMWPE stimulated pouches, and (3) EM markedly reduced the number of TRAP þ cells in pouch tissues, and protected against bone collagen depletion. In conclusion, this study provides the evidence that EM inhibits the UHMWPE particles-induced inflammatory osteolysis in a murine model, and represents a promising therapeutic candidate for the prevention and treatment of AL. ß

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“…In another study, OPG inhibited in vitro murine osteoclast formation induced by fluid from failed total hip arthroplasties [25]. In peri-implant tissues of patients with implant failure, high levels of RANKL was found compared to healthy subjects [26]. Macrophages were shown to be responsible for this increase.…”

Section: Introductionmentioning

confidence: 94%

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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Factors regulating osteoclast formation in human tissues adjacent to peri-implant bone loss: expression of receptor activator NFκB, RANK ligand and osteoprotegerin

Cited by 148 publications

References 36 publications

Implant wear induces inflammation, but not osteoclastic bone resorption, in RANK^–/– mice

Implant wear induces inflammation, but not osteoclastic bone resorption, in RANK^–/– mice

Erythromycin inhibits wear debris‐induced inflammatory osteolysis in a murine model

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

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Factors regulating osteoclast formation in human tissues adjacent to peri-implant bone loss: expression of receptor activator NFκB, RANK ligand and osteoprotegerin

Cited by 148 publications

References 36 publications

Implant wear induces inflammation, but not osteoclastic bone resorption, in RANK–/– mice

Implant wear induces inflammation, but not osteoclastic bone resorption, in RANK–/– mice

Erythromycin inhibits wear debris‐induced inflammatory osteolysis in a murine model

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

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Product

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Implant wear induces inflammation, but not osteoclastic bone resorption, in RANK^–/– mice

Implant wear induces inflammation, but not osteoclastic bone resorption, in RANK^–/– mice