Da Wacili, Tao Lin, Wen Kaicheng, Tao Zhengbo, Wang Shaojie, Zhu Yue
Department of Orthopedics, First Affiliated Hospital of China Medical University, Shenyang, China.
School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang, China.
Front Pharmacol. 2020 May 19;11:667. doi: 10.3389/fphar.2020.00667. eCollection 2020.
A negative correlation exists between the severity of osteoporosis and citrate levels in bone. Our previous research found that melatonin can significantly improve bone mass in mice with osteoporosis, but the underlying mechanism involving citrate remains unknown. Herein, we demonstrated that melatonin increased bone volume and citrate levels in ovariectomized osteoporosis mice. Melatonin increased citrate and mineralized nodules in osteoblasts induced from primary mouse bone marrow mesenchymal stem cells . ZIP-1 knockdown and overexpression confirmed that melatonin specifically upregulated ZIP-1 to rescue citrate levels and bone mass. In general, we verified that melatonin can improve bone mass by enhancing matrix mineralization, which is highly related to increased citrate secretion from osteoblasts, and that ZIP-1 is the target of melatonin. These findings reveal another role of melatonin in regulating bone remodeling and provide a research base for its possible application in the treatment of clinical osteoporosis in the future.
骨质疏松症的严重程度与骨中柠檬酸盐水平呈负相关。我们之前的研究发现，褪黑素可以显著改善骨质疏松症小鼠的骨量，但涉及柠檬酸盐的潜在机制尚不清楚。在此，我们证明褪黑素可增加去卵巢骨质疏松症小鼠的骨体积和柠檬酸盐水平。褪黑素增加了从小鼠原代骨髓间充质干细胞诱导的成骨细胞中的柠檬酸盐和矿化结节。ZIP-1基因敲低和过表达证实，褪黑素特异性上调ZIP-1以挽救柠檬酸盐水平和骨量。总体而言，我们证实褪黑素可通过增强基质矿化来改善骨量，这与成骨细胞柠檬酸盐分泌增加高度相关，并且ZIP-1是褪黑素的作用靶点。这些发现揭示了褪黑素在调节骨重塑中的另一个作用，并为其未来可能应用于临床骨质疏松症治疗提供了研究基础。
