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

Autor:	Miao Y; College of Food Science and Technology, Yunnan Agricultural University, Kunming, Yunnan, China.; Medicinal Plants Research Institute, Yunnan Academy of Agricultural Sciences, Kunming, Yunnan, China., Zhao L; College of Science, Yunnan Agricultural University, Kunming, China., Lei S; College of Food Science and Technology, Yunnan Agricultural University, Kunming, Yunnan, China., Zhao C; College of Food Science and Technology, Yunnan Agricultural University, Kunming, Yunnan, China., Wang Q; College of Food Science and Technology, Yunnan Agricultural University, Kunming, Yunnan, China., Tan C; College of Food Science and Technology, Yunnan Agricultural University, Kunming, Yunnan, China., Peng C; College of Horticulture and Landscape, Yunnan Agricultural University, Kunming, China., Gong J; College of Food Science and Technology, Yunnan Agricultural University, Kunming, Yunnan, China.; Agro-Products Processing Research Institute, Yunnan Academy of Agricultural Sciences, Kunming, China.
Jazyk:	angličtina
Zdroj:	Frontiers in pharmacology [Front Pharmacol] 2024 Jun 13; Vol. 15, pp. 1405173. Date of Electronic Publication: 2024 Jun 13 (Print Publication: 2024).
DOI:	10.3389/fphar.2024.1405173
Abstrakt:	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. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2024 Miao, Zhao, Lei, Zhao, Wang, Tan, Peng and Gong.)
Databáze:	MEDLINE
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