Fucoxanthin restores mitochondrial bioenergetics and attenuates dexamethasone-induced osteoblast Dysfunction: Implications for glucocorticoid-associated bone disorders

Dexamethasone (DEX), a widely used anti-inflammatory glucocorticoid, is associated with bone-related adverse effects. This study investigated the protective role of fucoxanthin (FX), a bioactive carotenoid, against DEX-induced bioenergetic disruption in human osteoblasts. DEX reduced osteoblast viability (48 h EC₅₀ = 20 μM), which FX (10–20 μM) counteracted. DEX (2–20 μM) impaired osteoblast function, marked by decreased secretion of procollagen type I, osteocalcin, and alkaline phosphatase, alongside reduced ATP levels, mitochondrial membrane potential (MMP), and oxygen consumption (OC). DEX also elevated lactate production, suppressed mitochondrial complexes I and III activities, and downregulated mitochondrial gene expressions (ND1, ND5, cytochrome b, cytochrome c oxidase, ATP synthase subunits 6/8). Additionally, DEX increased mitochondrial membrane fluidity, swelling, and H⁺/K⁺ permeability. FX attenuated these effects dose-dependently, restoring viability, secretory function, and bioenergetic parameters (ATP, MMP, OC) while mitigating mitochondrial structural and ionic disturbances. These findings highlight FX's potential to alleviate DEX-induced osteoblast dysfunction by preserving mitochondrial integrity and bioenergetics, suggesting its therapeutic utility in managing glucocorticoid-associated bone disorders.