Effects of benzotriazoles UV-328, UV-329, and UV-P on the self-renewal and adipo-osteogenic differentiation of human mesenchymal stem cells

Abstract

Benzotriazole ultraviolet stabilizers (BUVSs) are pervasive environmental contaminants that pose significant risks to human health. This study evaluated the effects of three typical BUVSs (UV-328, UV-329, and UV-P) on human mesenchymal stem cells (hMSCs), which play crucial roles in tissue maintenance and repair. hMSCs were exposed to BUVSs across a range of concentrations, and their maintenance and differentiation capacities were assessed. At concentrations below 50 μM, no significant cytotoxicity was observed. However, at non-cytotoxic doses, UV-P exhibited stronger effects on the differentiation of hMSCs compared to UV-328 and UV-329, significantly inhibiting adipogenesis and enhancing osteogenesis. Mechanistically, UV-P was found to significantly enrich the PPAR signaling pathway during both differentiation processes. Dual-luciferase reporter assays confirmed UV-P's interaction with PPARγ_LBD at an alternate binding site outside the canonical pocket. These findings raise concerns about the health impacts of BUVSs, particularly UV-P, and underscore the need for further investigation into their toxicological profiles.

Keywords

• Benzotriazole ultraviolet stabilizers
• Human mesenchymal stem cells
• Self-renewal
• Adipo-osteogenesis
• PPARγ