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c-FOS / NFATc1 신호 및 ROS 생성 억제를 통한 RANKL 유도 파골 세포 분화를 감소시키는 CK 베리 추출물의 효과
The Effects of CK berry’s Extract in Reducing RANKL-Induced Osteoclastic Differentiation by Inhibiting c-FOS/NFATc1 Signaling and ROS Generation
Background : This study aimed to determine the anti-osteoclastogenic effects of extracts from CK berry’s and identify the underlying mechanisms in vitro.
Methods and Results : Reactive oxygen species (ROS) are signal mediators in osteoclast differentiation. AM extracts inhibited ROS production in RAW264.7 cells in a dose-dependent manner and exhibited strong radical scavenging activity. The extracts also attenuated the number of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated osteoclasts. To attain molecular insights, the effect of the extracts on the signaling pathways induced by receptor activator of nuclear factor kappa B ligand (RANKL) were also investigated. RANKL triggers many transcription factors through the activation of mitogen-activated protein kinase (MAPK) and ROS, leading to the induction of osteoclast-specific genes. The extracts significantly suppressed RANKL-induced activation of MAPKs, such as extracellular signal-regulated kinase (ERK), c-Jun-N-terminal kinase (JNK), and p38, and consequently led to the downregulation of c-Fos and nuclear factor of activated T cells 1 (NFATc1) protein expression which ultimately suppress the activation of the osteoclast-specific genes, cathepsin K, TRAP, calcitonin receptor, and integrin β3.
Conclusion : In conclusion, our findings suggest that AM extracts inhibited RANKL-induced osteoclast differentiation by downregulating ROS generation and inactivating JNK/ERK/p38, nuclear factor kappa B (NF-κB)-mediated c-Fos and NFATc1 signaling pathway.
