Particulate wear debris activates protein tyrosine kinases and nuclear factor κB, which down-regulates type I collagen synthesis in human osteoblasts

C. Vermes, K. A. Roebuck, R. Chandrasekaran, J. G. Dobai, J. J. Jacobs, T. T. Glant

Research output: Contribution to journalArticle

92 Citations (Scopus)

Abstract

Particulate wear debris generated mechanically from prosthetic materials is phagocytosed by a variety of cell types within the periprosthetic space including osteoblasts, which cells with an altered function may contribute to periprosthetic osteolysis. Exposure of osteoblast-like osteosarcoma cells or bone marrow-derived primary osteoblasts to either metallic or polymeric particles of phagocytosable sizes resulted in a marked decrease in the steady-state messenger RNA (mRNA) levels of procollagen α1[I] and procollagen α1[III]. In contrast, no significant effect was observed for the osteoblast-specific genes, such as osteonectin and osteocalcin (OC). In kinetic studies, particles once phagocytosed, maintained a significant suppressive effect on collagen gene expression and type I collagen synthesis for up to five passages. Large particles of a size that cannot be phagocytosed also down-regulated collagen gene expression suggesting that an initial contact between cells and particles can generate gene responsive signals independently of the phagocytosis process. Concerning such signaling, titanium particles rapidly increased protein tyrosine phosphorylation and nuclear transcription factor κB (NF-κB) binding activity before the phagocytosis of particles. Protein tyrosine kinase (PTK) inhibitors such as genistein and the NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC) significantly reduced the suppressive effect of titanium on collagen gene expression suggesting particles suppress collagen gene expression through the NF-κB signaling pathway. These results provide a mechanism by which particulate wear debris can antagonize the transcription of the procollagen α1[I] gene in osteoblasts, which may contribute to reduced bone formation and progressive periprosthetic osteolysis.

Original languageEnglish
Pages (from-to)1756-1765
Number of pages10
JournalJournal of Bone and Mineral Research
Volume15
Issue number9
Publication statusPublished - 2000

Fingerprint

Collagen Type I
Osteoblasts
Phagocytosis
Protein-Tyrosine Kinases
Down-Regulation
Procollagen
Collagen
Gene Expression
Osteolysis
Transcription Factors
Titanium
Particle Size
Osteonectin
Genes
Genistein
Osteocalcin
Osteosarcoma
Protein Kinase Inhibitors
Osteogenesis
Bone Marrow Cells

Keywords

  • Nuclear factor κB
  • Osteoblast
  • Particulate
  • Phagocytosis
  • Procollagen α1[I] gene
  • Protein kinases

ASJC Scopus subject areas

  • Surgery

Cite this

Particulate wear debris activates protein tyrosine kinases and nuclear factor κB, which down-regulates type I collagen synthesis in human osteoblasts. / Vermes, C.; Roebuck, K. A.; Chandrasekaran, R.; Dobai, J. G.; Jacobs, J. J.; Glant, T. T.

In: Journal of Bone and Mineral Research, Vol. 15, No. 9, 2000, p. 1756-1765.

Research output: Contribution to journalArticle

Vermes, C. ; Roebuck, K. A. ; Chandrasekaran, R. ; Dobai, J. G. ; Jacobs, J. J. ; Glant, T. T. / Particulate wear debris activates protein tyrosine kinases and nuclear factor κB, which down-regulates type I collagen synthesis in human osteoblasts. In: Journal of Bone and Mineral Research. 2000 ; Vol. 15, No. 9. pp. 1756-1765.
@article{7b396ac6624340f0834d403d4c2eed39,
title = "Particulate wear debris activates protein tyrosine kinases and nuclear factor κB, which down-regulates type I collagen synthesis in human osteoblasts",
abstract = "Particulate wear debris generated mechanically from prosthetic materials is phagocytosed by a variety of cell types within the periprosthetic space including osteoblasts, which cells with an altered function may contribute to periprosthetic osteolysis. Exposure of osteoblast-like osteosarcoma cells or bone marrow-derived primary osteoblasts to either metallic or polymeric particles of phagocytosable sizes resulted in a marked decrease in the steady-state messenger RNA (mRNA) levels of procollagen α1[I] and procollagen α1[III]. In contrast, no significant effect was observed for the osteoblast-specific genes, such as osteonectin and osteocalcin (OC). In kinetic studies, particles once phagocytosed, maintained a significant suppressive effect on collagen gene expression and type I collagen synthesis for up to five passages. Large particles of a size that cannot be phagocytosed also down-regulated collagen gene expression suggesting that an initial contact between cells and particles can generate gene responsive signals independently of the phagocytosis process. Concerning such signaling, titanium particles rapidly increased protein tyrosine phosphorylation and nuclear transcription factor κB (NF-κB) binding activity before the phagocytosis of particles. Protein tyrosine kinase (PTK) inhibitors such as genistein and the NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC) significantly reduced the suppressive effect of titanium on collagen gene expression suggesting particles suppress collagen gene expression through the NF-κB signaling pathway. These results provide a mechanism by which particulate wear debris can antagonize the transcription of the procollagen α1[I] gene in osteoblasts, which may contribute to reduced bone formation and progressive periprosthetic osteolysis.",
keywords = "Nuclear factor κB, Osteoblast, Particulate, Phagocytosis, Procollagen α1[I] gene, Protein kinases",
author = "C. Vermes and Roebuck, {K. A.} and R. Chandrasekaran and Dobai, {J. G.} and Jacobs, {J. J.} and Glant, {T. T.}",
year = "2000",
language = "English",
volume = "15",
pages = "1756--1765",
journal = "Journal of Bone and Mineral Research",
issn = "0884-0431",
publisher = "Wiley-Blackwell",
number = "9",

}

TY - JOUR

T1 - Particulate wear debris activates protein tyrosine kinases and nuclear factor κB, which down-regulates type I collagen synthesis in human osteoblasts

AU - Vermes, C.

AU - Roebuck, K. A.

AU - Chandrasekaran, R.

AU - Dobai, J. G.

AU - Jacobs, J. J.

AU - Glant, T. T.

PY - 2000

Y1 - 2000

N2 - Particulate wear debris generated mechanically from prosthetic materials is phagocytosed by a variety of cell types within the periprosthetic space including osteoblasts, which cells with an altered function may contribute to periprosthetic osteolysis. Exposure of osteoblast-like osteosarcoma cells or bone marrow-derived primary osteoblasts to either metallic or polymeric particles of phagocytosable sizes resulted in a marked decrease in the steady-state messenger RNA (mRNA) levels of procollagen α1[I] and procollagen α1[III]. In contrast, no significant effect was observed for the osteoblast-specific genes, such as osteonectin and osteocalcin (OC). In kinetic studies, particles once phagocytosed, maintained a significant suppressive effect on collagen gene expression and type I collagen synthesis for up to five passages. Large particles of a size that cannot be phagocytosed also down-regulated collagen gene expression suggesting that an initial contact between cells and particles can generate gene responsive signals independently of the phagocytosis process. Concerning such signaling, titanium particles rapidly increased protein tyrosine phosphorylation and nuclear transcription factor κB (NF-κB) binding activity before the phagocytosis of particles. Protein tyrosine kinase (PTK) inhibitors such as genistein and the NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC) significantly reduced the suppressive effect of titanium on collagen gene expression suggesting particles suppress collagen gene expression through the NF-κB signaling pathway. These results provide a mechanism by which particulate wear debris can antagonize the transcription of the procollagen α1[I] gene in osteoblasts, which may contribute to reduced bone formation and progressive periprosthetic osteolysis.

AB - Particulate wear debris generated mechanically from prosthetic materials is phagocytosed by a variety of cell types within the periprosthetic space including osteoblasts, which cells with an altered function may contribute to periprosthetic osteolysis. Exposure of osteoblast-like osteosarcoma cells or bone marrow-derived primary osteoblasts to either metallic or polymeric particles of phagocytosable sizes resulted in a marked decrease in the steady-state messenger RNA (mRNA) levels of procollagen α1[I] and procollagen α1[III]. In contrast, no significant effect was observed for the osteoblast-specific genes, such as osteonectin and osteocalcin (OC). In kinetic studies, particles once phagocytosed, maintained a significant suppressive effect on collagen gene expression and type I collagen synthesis for up to five passages. Large particles of a size that cannot be phagocytosed also down-regulated collagen gene expression suggesting that an initial contact between cells and particles can generate gene responsive signals independently of the phagocytosis process. Concerning such signaling, titanium particles rapidly increased protein tyrosine phosphorylation and nuclear transcription factor κB (NF-κB) binding activity before the phagocytosis of particles. Protein tyrosine kinase (PTK) inhibitors such as genistein and the NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC) significantly reduced the suppressive effect of titanium on collagen gene expression suggesting particles suppress collagen gene expression through the NF-κB signaling pathway. These results provide a mechanism by which particulate wear debris can antagonize the transcription of the procollagen α1[I] gene in osteoblasts, which may contribute to reduced bone formation and progressive periprosthetic osteolysis.

KW - Nuclear factor κB

KW - Osteoblast

KW - Particulate

KW - Phagocytosis

KW - Procollagen α1[I] gene

KW - Protein kinases

UR - http://www.scopus.com/inward/record.url?scp=0033840505&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033840505&partnerID=8YFLogxK

M3 - Article

VL - 15

SP - 1756

EP - 1765

JO - Journal of Bone and Mineral Research

JF - Journal of Bone and Mineral Research

SN - 0884-0431

IS - 9

ER -