Chemokine IL-8 induction by particulate wear debris in osteoblasts is mediated by NF-κB

Abstract

Chemokines, or chemotactic cytokines, are major regulators of the inflammatory response and have been identified as pathogenic factors in the periprosthetic soft tissue. Particulate wear debris induced NF-KB activation, the major transcriptional regulator of IL-8 and MCP-1 pro-inflammatory genes and, indeed, both IL-8 and MCP-1 chemokine gene expressions were upregulated in titanium particulate-stimulated human osteoblasts. Here, we demonstrate that phagocytosed particles activate the IL-8 gene promQter via a NF-KB-mediated mechanism. Transfection of a dominant negative mutant IKBCX protein that cannot be serine phosphoryldted led to suppression of IL-8 promoter activity. The p651RelA NF-KB subunit activity was affected in both a time-and titanium particle concentration-dependent fashion. Titanium particles led to increased ERK, JNK, and p38 activation in MG-63 osteoblast cells, and IL-8 protein release was suppressed by specific inhibitors of the ERK and p38 MAPK pathways. Together, our results suggest that wear debris particles induce chemokine expression in osteoblasts via NF-KB-mediated transcriptional activation, which is controlled by the MAPK signal transduction pathway.

Dental implant surface treatments may modulate cytokine secretion in Porphyromonas gingivalis‐stimulated human gingival fibroblasts: A comparative study

“…31,32 Evidently, pro-inflammatory cytokines were highly expressed in human osteoblasts in response to Ti particles via the nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-jB) pathway. 33 This is also in accordance with our results where elevated levels of IL-6, IL-8, and MCP-1were produced from HGFs (2LPS or 1LPS) that were incubated in titaniumbased implants when compared to polystyrene controls. Together, these studies support the idea that Ti debris released from an implant surface may be responsible for modulating cytokine secretion.…”

“…Although TiO 2 is thought to be corrosion‐resistant 4 , previous findings unveiled that titanium (Ti) particles in the peri‐implant tissue can induce a pro‐inflammatory response in peri‐implant granulation tissue fibroblasts (PIGF) . Evidently, pro‐inflammatory cytokines were highly expressed in human osteoblasts in response to Ti particles via the nuclear factor kappa‐light‐chain‐enhancer of activated B‐cells (NF‐κB) pathway . This is also in accordance with our results where elevated levels of IL‐6, IL‐8, and MCP‐1were produced from HGFs (−LPS or +LPS) that were incubated in titanium‐based implants when compared to polystyrene controls.…”

Antigenic Phenotype and Phagocytic Capacity of MG‐63 Osteosarcoma Line

“…The human MG-63 osteosarcoma cell line is frequently used as an in vitro model to study the effects on human osteoblasts of different substances, including hormones, growth factors, or drugs, and to investigate the influence on osseointegration of their proliferation and adhesion to biomaterial surfaces, among other factors. [1][2][3][4][5] Osteoblasts have a similar antigenic profile to that of other cells with immunogenic capacity. They express CD10 and CD13 antigens, molecules with aminopeptidase activity associated with cells of myelomonocytic lineage.…”

“…The human MG‐63 osteosarcoma cell line is frequently used as an in vitro model to study the effects on human osteoblasts of different substances, including hormones, growth factors, or drugs, and to investigate the influence on osseointegration of their proliferation and adhesion to biomaterial surfaces, among other factors 1–5 …”

Differences in the surface composition of seemingly similar F75 cobalt–chromium micron-sized particulates can affect synovial fibroblast viability

“…Phagocytosable metal wear debris particulates (appropriate for engulfment by a cell) have been identified as contributing factors in the development of inflammatory metal sensitivity and aseptic osteolysis (bone loss) around prosthetic implants, resulting, in some cases, in the loosening of the components and failure of the replacement [4][5][6][7][8]. Once phagocytosed, these particulates are thought to invoke histochemical up or down regulation, as well as apoptotic and/or necrotic effects on a multitude of cells found in the bone and soft tissues that surround the prosthetic implant [4,[9][10][11].…”