Roles of Del-1 in effects of hyponatremia on muscle and bone in mice

Hyponatremia induces both osteoporosis and sarcopenia. Although interactions between muscle and bone have been extensively examined, the myokines affecting bone in the hyponatremic state remain unclear. Therefore, we herein investigated myokines linking muscle to bone in the hyponatremic state using mice treated with 1-desamino-8-D-arginine vasopressin (dDAVP) and furosemide for 8 weeks. An RNA-sequencing analysis showed that the expression of developmental endothelial locus-1 (Del-1), a humoral factor, was down-regulated by hyponatremia in the gastrocnemius muscles of mice. dDAVP and furosemide significantly reduced Del-1 expression in the gastrocnemius and soleus muscles as well as circulating Del-1 levels in mice. Low sodium concentrations also decreased Del-1 expression in mouse myoblasts and myotubes. Del-1 significantly suppressed osteoclast formation in mouse bone marrow cells. A simple regression analysis revealed that serum Del-1 levels and Del-1 mRNA levels in the gastrocnemius muscle were positively correlated with trabecular bone volume fraction and cortical bone mineral density in mice. In conclusion, we herein identified Del-1 as a myokine linking muscle to bone in hyponatremia. The present results suggest that decreased expression of Del-1 in skeletal muscles might contribute to hyponatremia-induced bone loss in mice.