PDF(Pubmed)
Abstract：
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 μg/mL caffeine inhibited RANKL-mediated osteoclastogenesis in RAW 264.7 cells through the MAPK and NF-κB pathways, accompanied by the inactivation of nuclear translocation of nuclear factor NFATc1. Similarly, 3.125 and 12.5 μg/mL of caffeine modulated MC3T3-E1 osteogenesis via the AKT, MAPK, and NF-κB pathways. However, 50 μg/mL of caffeine promoted the phosphorylation of IκBα, 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.
摘要：
背景：虽然咖啡因通常对人类健康有益，其对骨代谢的影响尚不清楚。目的和方法：本研究旨在系统评价咖啡因给药对破骨细胞的长期影响。成骨细胞，和卵巢切除术引起的绝经后骨质疏松症（OP）。结果：我们的体外研究结果表明，3.125和12.5μg/mL咖啡因通过MAPK和NF-κB途径抑制RAW264.7细胞中RANKL介导的破骨细胞生成。伴有核因子NFATc1的核易位失活。同样，3.125和12.5μg/mL咖啡因通过AKT调节MC3T3-E1成骨，MAPK,和NF-κB通路。然而,50μg/mL咖啡因促进IκBα磷酸化,P65,JNK,P38和AKT,随后是NFATc1的激活和Runx2和Osterix的失活，最终破坏成骨细胞生成和破骨细胞生成之间的平衡。体内研究表明，用55.44mg/kg咖啡因灌胃抑制破骨细胞生成，促进成骨，并改善了去卵巢小鼠的骨丢失。结论：相反，长期摄入高剂量咖啡因（110.88mg/kg）会破坏成骨活性并促进破骨细胞生成，从而扰乱骨骼稳态。总的来说，这些发现表明，适量的咖啡因摄入（人类约400毫克）可以通过影响破骨细胞和成骨细胞来调节骨稳态。然而,长期高剂量咖啡因摄入(人体约800毫克)可能对骨骼系统产生不利影响.
