Osteoclasts are capable of adhering the bone matrix, then secrete acid and lytic enzymes to resorb it. Reactive oxygen species (ROS), as a signaling messenger, plays an important role in the receptor activator nuclear factor κB ligand (RANKL) signal pathway during osteoclast differentiation. Glutathione (GSH) is known to be a powerful antioxidant which can scavenge intracellular ROS. This study aimed to investigate whether GSH can as a protective agent against the RANKL-stimulated osteoclastogenesis by suppressing intracellular ROS. Here, we showed that GSH markedly restricted RNAKL-induced differentiation of bone marrow-derived macrophages (BMMs) to form osteoclasts. GSH suppressed RANKL-induced ROS generation and subsequent ROS-induced NF-κB signaling pathways within BMMs during osteoclastogenesis. Further, GSH acted to significantly downregulate the osteoclastogenic genes expression of nuclear factor in activated T cells, cytoplasmic1 (NFATc1), C-fos, the tartrate-resistant acid phosphatase (TRAP), and osteoclast-associated immunoglobulin-like receptor (OSCAR). Our results suggested that GSH inhibits intracellular ROS-mediated NF-κB signal pathway involved in osteoclast differentiation. These findings might form the basis of a new strategy for treating bone disease associated with excessive bone resorption.

破骨细胞能够粘附骨基质，然后分泌酸和裂解酶使其吸收。活性氧（ROS）作为信号传递信使，在破骨细胞分化过程中的受体活化剂核因子κB配体（RANKL）信号途径中起重要作用。谷胱甘肽（GSH）是一种强大的抗氧化剂，可以清除细胞内ROS。这项研究旨在调查GSH是否可以通过抑制细胞内ROS作为抗RANKL刺激的破骨细胞生成的保护剂。在这里，我们表明GSH明显限制了RNAKL诱导的骨髓巨噬细胞（BMM）分化以形成破骨细胞。GSH抑制破骨细胞形成过程中BMM中RANKL诱导的ROS生成以及随后ROS诱导的NF-κB信号通路。进一步，GSH的作用是显着下调活化T细胞，胞质1（NFATc1），C-fos，抗酒石酸酸性磷酸酶（TRAP）和破骨细胞相关的免疫球蛋白样受体（OSCAR）中破骨细胞生成基因的核因子表达。我们的结果表明，GSH抑制破骨细胞分化中涉及的细胞内ROS介导的NF-κB信号通路。这些发现可能构成治疗与过度骨吸收有关的骨病新策略的基础。