Cobalt ions are the main wear particles associated with orthopaedic implants, causing adverse complications due to cytotoxicity and inflammatory mediators. Recent studies have shown that sub-toxic levels of cobalt ions regulate matrix synthesis and inflammation, but the influence of cobalt ions on mechanotransduction remains unclear. Previously, we reported that sub-toxic levels of cobalt ions modulated primary cilia, which are crucial for mechanotransduction. This study therefore aimed to investigate the effect of cobalt ions on chondrocyte mechanosensation in response to cyclic tensile strain and the association with primary cilia. Sub-toxic levels of cobalt ions impaired chondrocyte mechanosensation and affected the gene expression of aggrecan, collagen II and MMP-13. Moreover, cobalt ions induced HDAC6-dependent primary cilia disassembly, which was associated with either cytoplasmic or ciliary alpha-tubulin deacetylation. Pharmaceutical HDAC6 inhibition with tubacin restored primary cilia length and mechanotransduction, whereas chemical depletion of primary cilia by chloral hydrate prevented mechanosignalling. Thus, sub-toxic levels of cobalt ions impaired chondrocyte mechanotransduction via HDAC6 activation, which was associated with tubulin deacetylation and primary cilia shortening. (C) 2021 Elsevier Inc. All rights reserved.