UHMWPE wear debris upregulates mononuclear cell proinflammatory gene expression in a novel murine model of intramedullary particle disease

Epstein, Noah J.; Bragg, William E.; Ma, Ting; Spanogle, Joshua P.; Smith, Robert L.; Goodman, Stuart B.

doi:10.1080/17453670510041321

Cited by 26 publications

(26 citation statements)

References 44 publications

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“…Our data on in vitro organ culture experiments is in agreement with the osteolysis severity and osteoclastogenesis analysis. Because IL-1 plays an important role in mediating TNF-a induced osteoclastogenesis, so the difference in the levels of IL-1b secreted into the culture medium may in part explain the osteolysis and osteoclastogenesis difference among these three groups of mice after UHMWPE particles implantation [15,16,17]. Surprisingly, we did not find any statistical dif-…”

Section: Figcontrasting

confidence: 51%

Influence of mouse genetic background on wear particle-induced in vivo inflammatory osteolysis

et al. 2008

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Section: Figcontrasting

confidence: 51%

Influence of mouse genetic background on wear particle-induced in vivo inflammatory osteolysis

et al. 2008

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“…Moreover, UHMWPE particles induce systemic macrophage recruitment 11–13 and pro-inflammatory cytokine release 14 resulting in osteolysis. 15,16 Once phagocytosis of UHMWPE particles occurs, macrophages release pro-inflammatory cytokines through NF-κB activation via several intracellular signal transduction pathways, inducing a series of biological events such as recruitment of more macrophages and osteoclast precursors, their differentiation 17 , and further release of cytokines and chemokines.…”

Section: Introductionmentioning

confidence: 99%

Selective inhibition of the MCP‐1‐CCR2 ligand‐receptor axis decreases systemic trafficking of macrophages in the presence of UHMWPE particles

Gibon

Ren

et al. 2011

Journal Orthopaedic Research

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The biological mechanisms leading to periprosthetic osteolysis involve both chemokines and the monocyte/macrophage cell lineage. Whether MCP-1 plays a major role in macrophage recruitment in the presence of wear particles is unknown. We tested two hypotheses: (1) that exogenous local delivery of MCP-1 induces systematic macrophage recruitment and (2) that blockade of the MCP-1 ligand-receptor axis decreases macrophage recruitment and osteolysis in the presence of UHMWPE particles. Six groups of nude mice were used. We used non-invasive imaging to assay macrophage recruitment and osteolysis. A murine macrophage cell line and primary wild type and CCR2 knockout murine macrophages were used as the reporter cells. Particles were infused into the femoral canal. Bioluminescence and immunohistochemical staining were used to confirm the migration of reporter cells. Locally infused MCP-1 induced systemic macrophage trafficking to bone. Injection of MCP-1 receptor antagonist significantly decreased reporter cell recruitment to bone infused with UHMWPE particles and decreased osteolysis. Systemic migration of reporter cells to infused particles was decreased when the reporter cells were deficient in the CCR2 receptor. Interruption of the MCP-1 ligand-receptor axis appears to be a viable strategy to mitigate trafficking of macrophages and osteolysis due to UHMWPE particles.

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“…Transduction of nuclear factors induces release of pro-inflammatory cytokines (tumour necrosis factor (TNF)-a, interleukin (IL)-1, IL-6, prostaglandin E (PGE)-2, macrophage colony-stimulating factor (M-CSF), receptor activator of NFkB ligand (RANKL), etc.) [36,37]. These factors act in an autocrine and paracrine way [38] to induce a series of biological events such as recruitment of more macrophages and osteoclast precursors, their differentiation [39] and further release of cytokines, some of which have chemotactic properties (chemokines) [40].…”

Section: Interfering With Ongoing Migration Ofmentioning

confidence: 99%

Novel biological strategies for treatment of wear particle-induced periprosthetic osteolysis of orthopaedic implants for joint replacement

Goodman

Gibon

Pajarinen

et al. 2014

J. R. Soc. Interface.

120

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ReviewCite this article: Goodman SB et al. 2014 Novel biological strategies for treatment of wear particle-induced periprosthetic osteolysis of orthopaedic implants for joint replacement. J. R. Soc. Wear particles and by-products from joint replacements and other orthopaedic implants may result in a local chronic inflammatory and foreign body reaction. This may lead to persistent synovitis resulting in joint pain and swelling, periprosthetic osteolysis, implant loosening and pathologic fracture. Strategies to modulate the adverse effects of wear debris may improve the function and longevity of joint replacements and other orthopaedic implants, potentially delaying or avoiding complex revision surgical procedures. Three novel biological strategies to mitigate the chronic inflammatory reaction to orthopaedic wear particles are reported. These include (i) interference with systemic macrophage trafficking to the local implant site, (ii) modulation of macrophages from an M1 ( pro-inflammatory) to an M2 (anti-inflammatory, pro-tissue healing) phenotype in the periprosthetic tissues, and (iii) local inhibition of the transcription factor nuclear factor kappa B (NF-kB) by delivery of an NF-kB decoy oligodeoxynucleotide, thereby interfering with the production of pro-inflammatory mediators. These three approaches have been shown to be viable strategies for mitigating the undesirable effects of wear particles in preclinical studies. Targeted local delivery of specific biologics may potentially extend the lifetime of orthopaedic implants.

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UHMWPE wear debris upregulates mononuclear cell proinflammatory gene expression in a novel murine model of intramedullary particle disease

Cited by 26 publications

References 44 publications

Influence of mouse genetic background on wear particle-induced in vivo inflammatory osteolysis

Influence of mouse genetic background on wear particle-induced in vivo inflammatory osteolysis

Selective inhibition of the MCP‐1‐CCR2 ligand‐receptor axis decreases systemic trafficking of macrophages in the presence of UHMWPE particles

Novel biological strategies for treatment of wear particle-induced periprosthetic osteolysis of orthopaedic implants for joint replacement

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