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Titanium Dioxide Particle Size Influences Macrophage Signal Switch Towards Osteogenesis In Vitro

Year: 2026
Type: article
Abstract: Objective The aim of this study was to investigate the impact of titanium dioxide microparticles (TiO 2 MPs) and titanium dioxide nanoparticles (TiO 2 NPs) on macrophage internalisation and their downstream influence on regulating osteogenesis in vitro. Design The viability of THP-1–derived macrophages exposed to TiO 2 MPs and TiO 2 NPs was evaluated using XTT assays. Conditioned medium (CM) from macrophages treated with TiO 2 MPs and NPs was collected and applied to human osteoblast (HOB) cells, with their functionality analysed at gene and protein expression levels, receptor activator of nuclear factor kappa-B ligand/osteoprotegerin (RANKL/OPG) ratio, and matrix mineralisation. Results Both TiO 2 MPs and NPs were nontoxic even at 100 µg/mL. Exposure of HOB to MP and NP CM induced significant proinflammatory responses, including increased IL-1β and IL-8 expression, alongside elevated TNF-α cytokine and MMP8 release. The TiO 2 MP CM group elicited stronger inflammatory responses, whereas the TiO 2 NP CM group demonstrated enhanced osteogenic activity, evidenced by upregulation of RUNX2, increased alkaline phosphatase activity, collagen type I secretion, and extracellular matrix mineralisation, generating a lower RANKL/OPG ratio in HOB cells. Western blotting revealed elevated osteocalcin and BMP-7 levels in NP CM-treated cells. Conclusion Titanium dioxide particle sizes are able to “switch” macrophage signalling toward either bone formation (nano) or bone resorption (micro) and may play a crucial role in osteo-immunomodulation.
Language: English
Open Access status: gold
Estimated APC paid: $2,550
Award: G286549553
OpenAlex ID: W7161601586
FWCI:
Cites: 19
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