ArticleBiological trace element research2026
Copper Promotes Myogenic Differentiation of Bovine Skeletal Muscle-Derived Cells by Activating the HIF-1α/β-catenin Signaling Axis.
Article in Biological trace element research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Copper is an essential trace element for beef cattle, yet its muscle developmental regulatory mechanism remains unclear. This study investigated the effects of copper sulfate (CuSO₄) on myogenic differentiation of bovine skeletal muscle-derived cells (BSMC) and the underlying molecular mechanisms. BSMC were isolated from the longissimus thoracis muscle of three 30-month-old crossbred steers, with each steer defined as an independent experimental unit corresponding to a separate biological replicate (n = 3). Based on cell viability, CuSO₄ was used at 0, 0.1, 1, and 10 µM. All cell samples were harvested at differentiation day 6 (D6). The 0.1 µM CuSO₄ treatment during cell growth significantly promoted D6 myotube formation (P = 0.049), and upregulated mRNA and protein expression of myogenic differentiation 1 (MyoD) (P = 0.044, P = 0.030), as well as protein expression of hypoxia-inducible factor-1α (HIF-1α) (P = 0.037) and β-catenin (P = 0.050). During differentiation, 1 µM CuSO₄ significantly facilitated D6 myotube formation (P = 0.0004), increased myogenic factor 5(Myf5) mRNA and protein expression (P = 0.030, P = 0.006), and elevated HIF-1α (P = 0.025) and β-catenin (P = 0.004) protein levels, whereas Wnt10b protein expression remained unaltered (P = 0.930). Single or combined pharmacological inhibition of HIF-1α and β-catenin markedly reversed copper's pro-myogenic effect on BSMC. In conclusion, copper modulates BSMC myogenic differentiation via the HIF-1α/β-catenin axis by enhancing β-catenin protein stability independent of Wnt10b transcription. HIF-1α acts upstream to drive β-catenin, and a reciprocal regulatory relationship may exist in which β-catenin in turn helps sustain HIF-1α abundance, thereby supporting cascade signaling and downstream myogenic transcription. This study elucidates copper's molecular mechanism governing muscle development and provides theoretical support for precise copper supplementation to improve beef production performance.
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