Epoxyeicosanoids suppress osteoclastogenesis and prevent ovariectomy-induced bone loss

	Epoxyeicosanoids suppress osteoclastogenesis and prevent ovariectomy-induced bone loss
	Guan Hanfeng; Zhao Libo; Cao Huijuan; Chen, AM (Chen Anmin; Xiao Jun
刊名	FASEB JOURNAL
	2015
英文摘要	Epoxyeicosatrienoic acids (EETs) are products of arachidonic acid metabolism catalyzed by cytochrome P450 epoxygenases. These small molecules are autocrine and paracrine lipid mediators with important roles in inflammation, cardiovascular function, and angiogenesis. Recent evidence has highlighted EETs as potent promoters of organ regeneration and malignant metastasis. We speculated that EETs might impact osteoclastogenesis and bone loss. Using both in vitro and in vivo studies, we observed that EETs significantly attenuated bone loss and inhibited osteoclast formation and activity, which were associated with a decreased receptor activator of NF-kappa B ligand (RANKL): osteoprotegerin ratio and serum levels of TNF-alpha and IL-1 beta. At the molecular level, EETs abrogated RANKL-induced activation of NF-kappa B, activator protein-1 (AP-1), and MAPKs, including ERK and JNK, but not p38, during osteoclast formation. EETs also prevented the production of reactive oxygen species (ROS) following RANKL stimulation. As a result, EETs suppressed osteoclast-specific gene expression, including tartrate resistant acid phosphatase (TRAP), cathepsin K (CK), matrix metalloproteinase (MMP)-9, and receptor activator of NF-kappa B (RANK). In conclusion, our findings demonstrate that EETs inhibit osteoclastogenesis through modulation of multiple pathways both upstream and downstream of RANKL signaling. The administration or stabilized endogenous levels of EETs could represent a novel therapeutic strategy for osteoclast-related disorders, such as rheumatoid arthritis and postmenopausal osteoporosis
收录类别	SCI
原文出处	http://www.ncbi.nlm.nih.gov/pubmed/25466887
语种	英语
内容类型	期刊论文
源URL	[http://ir.siat.ac.cn:8080/handle/172644/7190]
专题	深圳先进技术研究院_医工所
作者单位	FASEB JOURNAL
推荐引用方式 GB/T 7714	Guan Hanfeng,Zhao Libo,Cao Huijuan,et al. Epoxyeicosanoids suppress osteoclastogenesis and prevent ovariectomy-induced bone loss[J]. FASEB JOURNAL,2015.
APA	Guan Hanfeng,Zhao Libo,Cao Huijuan,Chen, AM ,&Xiao Jun.(2015).Epoxyeicosanoids suppress osteoclastogenesis and prevent ovariectomy-induced bone loss.FASEB JOURNAL.
MLA	Guan Hanfeng,et al."Epoxyeicosanoids suppress osteoclastogenesis and prevent ovariectomy-induced bone loss".FASEB JOURNAL (2015).