A Novel Rhein Derivative Modulates Bone Formation and Resorption and Ameliorates Estrogen-Dependent Bone Loss

doi:10.1002/jbmr.3604

	A Novel Rhein Derivative Modulates Bone Formation and Resorption and Ameliorates Estrogen-Dependent Bone Loss
	Jiang, Min 2; Wang, Tianqi 2; Yan, Xueming 2; Liu, Zhuochao 2; Yan, Yufei 2; Yang, Kai 2; Qi, Jin 2; Zhou, Hanbing 2; Qian, Niandong 2; Zhou, Qi 2
刊名	Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
	2018-10-15
ISSN号	1523-4681
DOI	10.1002/jbmr.3604
文献子类	Article
英文摘要	Osteoporosis, an osteolytic disease that affects millions of people worldwide, features a bone remodeling imbalance between bone resorption by osteoclasts and bone formation by osteoblasts. Identifying dual target-directed agents that inhibit excessive bone resorption and increase bone formation is considered an efficient strategy for developing new osteoporosis treatments. Rhein, a natural anthraquinone, can be isolated from various Asian herbal medicines. Rhein and its derivatives have been reported to have various beneficial pharmacological effects, especially their bone-targeting ability and anti-osteoclastogenesis activity. Moreover, hydrogen sulfide (H S) was reported to prevent ovariectomy- (OVX-) induced bone loss by enhancing bone formation, and sulfur replacement therapy has been considered a novel and plausible therapeutic option. Based on this information, we synthesized a rhein-derived thioamide (RT) and investigated its effects on bone resorption and bone formation in vitro and in vivo. It has been found that the RT-inhibited receptor activator of the nuclear factor-κB (NF-κB) ligand- (RANKL-) induced osteoclastogenesis and bone resorption in a dose-dependent manner. The expression of osteoclast marker genes was also suppressed by RT treatment. Furthermore, exploration of signal transduction pathways indicated that RT markedly blocked RANKL-induced osteoclastogenesis by attenuating MAPK pathways. However, RT treatment in an osteoblastic cell line, MC3TE-E1, indicated that RT led to an increase in the deposition of minerals and the expression of osteoblast marker genes, as demonstrated by Alizarin Red staining and alkaline phosphatase activity. Importantly, an OVX mouse model showed that RT could attenuate the bone loss in estrogen deficiency-induced osteoporosis in vivo with a smart H S-releasing property and that there was a considerable improvement in the biomechanical properties of bone. Accordingly, our current work highlights the dual regulation of bone remodeling by the rhein-derived molecule RT. This may be a highly promising approach for a new type of anti-osteoporosis agent. © 2018 American Society for Bone and Mineral Research.
语种	英语
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/266320]
专题	药物化学研究室
作者单位	1.Department of Medicinal Chemistry, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China 2.Shanghai Key Laboratory for Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Shanghai Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China;
推荐引用方式 GB/T 7714	Jiang, Min,Wang, Tianqi,Yan, Xueming,et al. A Novel Rhein Derivative Modulates Bone Formation and Resorption and Ameliorates Estrogen-Dependent Bone Loss[J]. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research,2018.
APA	Jiang, Min.,Wang, Tianqi.,Yan, Xueming.,Liu, Zhuochao.,Yan, Yufei.,...&Deng, Lianfu.(2018).A Novel Rhein Derivative Modulates Bone Formation and Resorption and Ameliorates Estrogen-Dependent Bone Loss.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.
MLA	Jiang, Min,et al."A Novel Rhein Derivative Modulates Bone Formation and Resorption and Ameliorates Estrogen-Dependent Bone Loss".Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research (2018).