Kawao Naoyuki, Nishikawa Akihito, Matsumura Daichi, Yamada Ayaka, Ohira Takashi, Mizukami Yuya, Kaji Hiroshi
Department of Physiology and Regenerative Medicine, Faculty of Medicine, Kindai University, 377-2 Ohnohigashi, Osakasayama, Osaka, 589-8511, Japan.
Department of Orthopaedic Surgery, Faculty of Medicine, Kindai University, Osakasayama, Japan.
Calcif Tissue Int. 2025 Apr 14;116(1):61. doi: 10.1007/s00223-025-01369-7.
Hyponatremia is associated with sarcopenia and osteoporosis in elderly individuals. Skeletal muscle releases myokines, which affect distant organs, including bone. However, the detailed mechanisms by which hyponatremia influences muscle and bone remain unclear. We herein investigated the effects of hyponatremia on muscle, bone, and myokines linking muscle to bone in mice treated with 1-desamino-8-D-arginine vasopressin (dDAVP) or furosemide, which induce hyponatremia. Muscle mass and bone mineral density (BMD) were analyzed 8 weeks after the administration of dDAVP or furosemide. dDAVP significantly reduced grip strength, but did not affect tissue weights of gastrocnemius or soleus muscles of mice. Furosemide significantly decreased muscle mass, tissue weights of gastrocnemius and soleus muscles, and grip strength in mice. dDAVP and furosemide decreased trabecular BMD, trabecular bone volume, and cortical BMD at the femurs. Among myokines linking muscle to bone, hyponatremia reduced expression of insulin-like growth factor (IGF)-1 in gastrocnemius and soleus muscles and serum IGF-1 levels in mice. In simple regression analyses, serum IGF-1 levels were positively related to muscle IGF-1 expression, trabecular bone volume, and cortical BMD in mice. The administration of sodium chloride solution to mice ameliorated the decreases in grip strength, muscle mass, trabecular bone volume, cortical BMD, and the levels of muscle and circulating IGF-1 in furosemide-treated mice. The present study demonstrated that hyponatremia induces muscle and bone loss as well as a decrease in muscle IGF-1 expression in mice. The present findings suggest that IGF-1 might be related to muscle wasting and bone loss induced by hyponatremia in mice.
低钠血症与老年个体的肌肉减少症和骨质疏松症相关。骨骼肌释放肌动蛋白，其会影响包括骨骼在内的远处器官。然而，低钠血症影响肌肉和骨骼的详细机制仍不清楚。我们在此研究了低钠血症对用1-去氨基-8-D-精氨酸血管加压素（dDAVP）或速尿处理的小鼠的肌肉、骨骼以及连接肌肉与骨骼的肌动蛋白的影响，dDAVP或速尿会诱发低钠血症。在给予dDAVP或速尿8周后分析肌肉质量和骨矿物质密度（BMD）。dDAVP显著降低握力，但不影响小鼠腓肠肌或比目鱼肌的组织重量。速尿显著降低小鼠的肌肉质量、腓肠肌和比目鱼肌的组织重量以及握力。dDAVP和速尿降低了股骨的小梁BMD、小梁骨体积和皮质BMD。在连接肌肉与骨骼的肌动蛋白中，低钠血症降低了小鼠腓肠肌和比目鱼肌中胰岛素样生长因子（IGF）-1的表达以及血清IGF-1水平。在简单回归分析中，血清IGF-1水平与小鼠肌肉IGF-1表达、小梁骨体积和皮质BMD呈正相关。给小鼠注射氯化钠溶液可改善速尿处理小鼠的握力、肌肉质量、小梁骨体积、皮质BMD以及肌肉和循环IGF-1水平的下降。本研究表明，低钠血症会导致小鼠肌肉和骨质流失以及肌肉IGF-1表达降低。本研究结果表明，IGF-1可能与小鼠低钠血症诱导的肌肉萎缩和骨质流失有关。
