Distinct Concentration-Dependent Molecular Pathways Regulate Bone Cell Responses to Cobalt and Chromium Exposure from Joint Replacement Prostheses

Systemic cobalt (Co) and chromium (Cr) concentrations may be elevated in patients with metal joint replacement prostheses. Several studies have highlighted the detrimental effects of this exposure on bone cells vitro, but underlying mechanisms remain unclear. In study, we use whole-genome microarrays to comprehensively assess gene expression primary human osteoblasts, osteoclast precursors mature resorbing osteoclasts following clinically relevant circulating versus local periprosthetic tissue Co2+ Cr3+ ions CoCr nanoparticles. We also describe response osteoblasts routinely used prosthesis surfaces presence exposure. Our results suggest that systemic levels no effect primarily inhibit differentiation function via altering focal adhesion extracellular matrix interaction pathways. contrast, both osteoblast activity by HIF-1? signaling endocytic/cytoskeletal genes respectively, as well increasing inflammatory mechanistic implications for adverse reactions debris. Furthermore, identify clusters KEGG pathways which correlates Co2+:Cr3+ concentrations, has potential serve early markers toxicity. Finally, our study provides a molecular basis improved clinical outcomes hydroxyapatite-coated prostheses elicit pro-survival osteogenic signature compared grit-blasted plasma-sprayed titanium-coated