Caffeine regulates both osteoclast and osteoblast differentiation via the AKT, NF-κB, and MAPK pathways

文献类型： 外文期刊

第一作者： Miao, Yue

作者： Miao, Yue;Lei, Shuwen;Zhao, Chunyan;Wang, Qiuping;Tan, Chao;Gong, Jiashun;Miao, Yue;Zhao, Lei;Peng, Chunxiu;Gong, Jiashun

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关键词： caffeine; osteoclasts; osteoblasts; bone metabolism; ovariectomy

期刊名称：FRONTIERS IN PHARMACOLOGY （ 影响因子：4.4； 五年影响因子：5.0 ）

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年卷期： 2024 年 15 卷

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收录情况： SCI

摘要： Background: Although caffeine generally offers benefits to human health, its impact on bone metabolism remains unclear.Aim and Methods: This study aimed to systematically evaluate the long-term effects of caffeine administration on osteoclasts, osteoblasts, and ovariectomy-induced postmenopausal osteoporosis (OP).Results: Our in vitro findings revealed that 3.125 and 12.5 mu g/mL caffeine inhibited RANKL-mediated osteoclastogenesis in RAW 264.7 cells through the MAPK and NF-kappa B pathways, accompanied by the inactivation of nuclear translocation of nuclear factor NFATc1. Similarly, 3.125 and 12.5 mu g/mL of caffeine modulated MC3T3-E1 osteogenesis via the AKT, MAPK, and NF-kappa B pathways. However, 50 mu g/mL of caffeine promoted the phosphorylation of I kappa B alpha, P65, JNK, P38, and AKT, followed by the activation of NFATc1 and the inactivation of Runx2 and Osterix, ultimately disrupting the balance between osteoblastogenesis and osteoclastogenesis. In vivo studies showed that gavage with 55.44 mg/kg caffeine inhibited osteoclastogenesis, promoted osteogenesis, and ameliorated bone loss in ovariectomized mice.Conclusion: Conversely, long-term intake of high-dose caffeine (110.88 mg/kg) disrupted osteogenesis activity and promoted osteoclastogenesis, thereby disturbing bone homeostasis. Collectively, these findings suggest that a moderate caffeine intake (approximately 400 mg in humans) can regulate bone homeostasis by influencing both osteoclasts and osteoblasts. However, long-term high-dose caffeine consumption (approximately 800 mg in humans) could have detrimental effects on the skeletal system.

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