Skipjack tuna bone derived biocalcium ameliorates C2C12 myotube atrophy through microRNA29b regulation

We investigated the protective effects of skipjack tuna (Katsuwonus pelamis) bone-derived biocalcium (Bio) against dexamethasone-induced atrophy in C2C12 myotubes. Bio rescued atrophic morphology, increasing myotube diameter dose-dependently. It mitigated inflammation by suppressing nitric oxide production and the expression and concentration of proinflammatory cytokines (IL-6, TNF-α, IL-1β) significantly and dose-dependently. Bio restored protein turnover balance by downregulating MuRF1 and atrogin-1 while upregulating MTOR. At 5-20 µg/mL, Bio downregulated total NF-κB p65, p38 mitogen-activated protein kinase (MAPK), and FoxO3a and upregulated Akt expression. Crucially, Bio dose-dependently downregulated primary-, precursor-, and mature-microRNA-29b. In Bio-treated, dexamethasone-treated C2C12 myotubes, microRNA-29b inhibitor co-transfection significantly increased myogenin and MyoD expression, whereas microRNA-29b mimic co-transfection suppressed these myogenic markers, confirming the inhibitory role of microRNA-29b. Molecular docking simulations confirmed strong binding affinities between microRNA-29b and myogenin/MyoD. These results demonstrate that Bio exerts anti-atrophy effects by disrupting the microRNA-29b-mediated block on myogenesis and modulating inflammatory responses, protein turnover, and key signaling pathways. Collectively, skipjack tuna-derived Bio shows promise as a functional food supplement for sarcopenia prevention and management.