Chondrocyte Viability and Function is Impaired by E-Cigarette Liquid Flavor Additives.

INTRODUCTION: Environmental factors, such as inhaled chemical agents, may pose risks to cartilage tissue and embedded chondrocytes. Increasingly used among adolescents and young adults, electronic cigarettes (e-cigarettes) utilize aerosols rich in chemical flavoring agents that contact the respiratory epithelium and may adversely affect underlying airway structures, including chondrocyte-containing cartilage. This study evaluated the effect of common e-cigarette flavorings on chondrocyte viability and function using the ATDC5 cell line as a chondrocyte model. METHODS: ATDC5 cells were exposed to increasing concentrations of nicotine-free e-cigarette liquid flavor additives (ELFAs) introduced into the media, followed by assessment of cellular metabolism, cellular membrane integrity, functional activity, inflammatory response, and gene expression profiling. RESULTS: Significant cytotoxicity was observed in Cinnamon- and Menthol-treated groups, with near-complete loss of cell viability at concentrations ≥4%. These additives also induced dysregulation of chondrocyte matrix metabolism and increased expression of cyclo-oxygenase-2 activity, notably displaying significant upregulation of matrix metalloproteinase-13 (MMP-13) and prostaglandin E2, respectively. CONCLUSIONS: Our findings show that commonly used ELFAs may alter chondrocyte metabolism, function, gene expression, and inflammatory signaling in a flavor‑ and concentration‑dependent manner, underscoring the need for deeper investigation into how e‑cigarette flavor additives affect cellular and tissue health.