期刊
AMINO ACIDS
卷 46, 期 11, 页码 2605-2614出版社
SPRINGER WIEN
DOI: 10.1007/s00726-014-1797-9
关键词
Polyamines; Preosteoclast; Fusion; Migration; NFATc1; PYK2; Calcium
资金
- Korea Research Institute of Chemical Technology project's grant [SI-1304]
- Inter-ER Cooperation Projects of Korea Institute for Advancement of Technology - Korea Ministry of Knowledge Economy [R0002019]
- National Research Council of Science & Technology (NST), Republic of Korea [SI-1304] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Natural polyamines have numerous biological activities. Several studies have reported their beneficial role in bone metabolism, but their mode of action is not fully understood. Bone diseases such as osteoporosis, which is characterized by impaired bone structure and low bone mass, are caused by an increased number of osteoclasts and/or overactivation of osteoclastogenesis. Osteoclast differentiation is a multi-complex procedure involving the following sequential steps: differentiation-migrationfusion- resorption. In this study, we found that putrescine, spermidine or spermine inhibited the RANKL-mediated migration of preosteoclasts. Furthermore, the RANKL-mediated activation of the Src-PYK2 signaling axis and of transcription factors such as NF-kappa B and NFATc1 was prevented by each polyamine. Anti-osteoclastogenic and anti-migration activities of polyamines were confirmed by evaluating their potential to downregulate the mRNA expression levels of osteoclastogenesis-related genes such as OSCAR, TRAP, cathepsin K and c-Src, and genes related to fusion and/or migration of preosteoclasts. Moreover, ATP-mediated elevation of cytosolic free Ca2+ concentration ([Ca2+](i)) was strongly inhibited by each polyamine, indicating the involvement of [Ca2+](i) in the anti-fusion activities of polyamines. In conclusion, polyamines could exhibit anti-osteoclastogenic activity by inhibiting the migration of preosteoclasts via the Ca2+-PYK2-Src-NFATc1 signaling axis.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据