Particulate wear debris activates protein tyrosine kinases and nuclear factor kappaB, 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 alpha1[I] and procollagen alpha1[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 kappaB (NF-kappaB) binding activity before the phagocytosis of particles. Protein tyrosine kinase (PTK) inhibitors such as genistein and the NF-kappaB inhibitor pyrrolidine dithiocarbamate (PDTC) significantly reduced the suppressive effect of titanium on collagen gene expression suggesting particles suppress collagen gene expression through the NF-kappaB signaling pathway. These results provide a mechanism by which particulate wear debris can antagonize the transcription of the procollagen alpha1[I] gene in osteoblasts, which may contribute to reduced bone formation and progressive periprosthetic osteolysis.

• Authors: C Vermes, K A Roebuck, R Chandrasekaran, J G Dobai, J J Jacobs, T T Glant
• Journal: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research (J Bone Miner Res) Vol. 15 Issue 9 Pg. 1756-65 (Sep 2000) ISSN: 0884-0431 [Print] United States
• PMID: 10976995 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Cytokines
• Metals
• NF-kappa B
• Polymers
• Procollagen
• RNA, Messenger
• Collagen
• DNA
• Protein-Tyrosine Kinases

Topics

• Cell Survival (drug effects)
• Collagen (biosynthesis, genetics)
• Cytokines (metabolism, pharmacology)
• DNA (genetics, metabolism)
• Down-Regulation (drug effects)
• Enzyme Activation (drug effects)
• Humans
• Metals (metabolism, pharmacology)
• NF-kappa B (antagonists & inhibitors, metabolism)
• Osteoblasts (cytology, drug effects, enzymology, metabolism)
• Particle Size
• Phagocytosis
• Phosphorylation (drug effects)
• Polymers (metabolism, pharmacology)
• Procollagen (biosynthesis, genetics, metabolism)
• Prostheses and Implants (adverse effects)
• Protein-Tyrosine Kinases (antagonists & inhibitors, metabolism)
• RNA, Messenger (genetics, metabolism)
• Signal Transduction (drug effects)
• Tumor Cells, Cultured