Zhejiang Hospital of Integrated Traditional Chinese and Western Medicine, Hangzhou, China.
The Third Clinical College of Zhejiang Chinese Medical University, Hangzhou, China.
Front Endocrinol (Lausanne). 2022 Dec 19;13:963237. doi: 10.3389/fendo.2022.963237. eCollection 2022.
Osteoporosis is a common metabolic bone disease with a rapidly increasing prevalence, characterized by massive bone loss because of excessive osteoclast formation. Gallic acid (GA), a phenolic acid isolated from , has anti-inflammatory and anti-oxidant effects, but its effect on osteoclast formation has not been confirmed. In our study, we demonstrated that GA significantly inhibited RANKL-induced osteoclast formation and function of osteoclast in bone marrow monocytes (BMMs) and RAW264.7 cells in a dose-dependent manner without cytotoxicity. For molecular mechanisms, GA repressed osteoclastogenesis by blocking Akt, ERK, and JNK pathways, and suppressed osteoclastogenesis-related marker expression, including nuclear factor of the activated T-cell cytoplasmic 1 (NFATc1), c-Fos, and cathepsin K (CTSK). In addition, we further assessed the effect of GA in an ovariectomized mouse model, which indicated that GA has a notable effect on preventing bone loss. In conclusion, GA exerts notable effects in inhibiting osteoclastogenesis and preventing ovariectomy-induced bone loss, suggesting that GA is a potential agent in osteoporosis treatment.
骨质疏松症是一种常见的代谢性骨病，其患病率迅速增加，其特征是由于破骨细胞形成过多而导致大量骨质流失。没食子酸（GA）是一种从 中分离出的酚酸，具有抗炎和抗氧化作用，但尚未证实其对破骨细胞形成的影响。在我们的研究中，我们证明 GA 可显著抑制 RANKL 诱导的破骨细胞形成，并在不具有细胞毒性的情况下剂量依赖性地抑制破骨细胞在骨髓单核细胞（BMM）和 RAW264.7 细胞中的功能。对于分子机制，GA 通过阻断 Akt、ERK 和 JNK 途径来抑制破骨细胞生成，并抑制破骨细胞生成相关标志物的表达，包括激活 T 细胞胞浆核因子 1（NFATc1）、c-Fos 和组织蛋白酶 K（CTSK）。此外，我们进一步评估了 GA 在去卵巢小鼠模型中的作用，结果表明 GA 对预防骨丢失有显著作用。总之，GA 可显著抑制破骨细胞生成并预防去卵巢引起的骨丢失，表明 GA 是骨质疏松症治疗的一种潜在药物。
