Recombinant Human KAI1/CD82 Attenuates Glucocorticoid-Induced Muscle Atrophy by Promoting Myogenic Differentiation

Sarcopenia and glucocorticoid-induced myopathy are significant forms of muscle atrophy that pose considerable public health challenges. In this regard, preventing muscle atrophy is crucial for enhancing quality of life and increasing life expectancy. In this study, we investigated the effect of recombinant human KAI1 (<i>rh</i>KAI1) on myogenic differentiation and its protective effect against dexamethasone-induced muscle atrophy. <i>rh</i>KAI1 enhanced myogenic differentiation in both murine C2C12 myoblasts and primary human endometrial stromal cells, as evidenced by upregulation of myogenic regulatory factors and increased myotube formation. These effects were accompanied by increased phosphorylation of Akt and AMPK. In a dexamethasone (Dex)-induced atrophy model, <i>rh</i>KAI1 increased myotube diameter, restored MyHC expression, and reduced the expression of the E3 ligase atrogin-1, accompanied by increased phosphorylation of Akt and AMPK. In addition, <i>rh</i>KAI1 administration improved Dex-induced functional impairment in mice, as reflected by increased grip strength and improved rotarod performance. Molecular analyses further showed that <i>rh</i>KAI1 modulated Dex-induced fiber-type-related gene expression by restoring MYH7 (type I) and reducing MYH4 (type IIb) expression. Collectively, our findings demonstrate that <i>rh</i>KAI1 promotes myogenic differentiation and alleviates several functional and molecular features associated with glucocorticoid-induced muscle deterioration. These results support the potential of <i>rh</i>KAI1 as a candidate molecule for further investigation in steroid-induced muscle dysfunction.