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Arctiin abrogates osteoclastogenesis and bone resorption via suppressing RANKL-induced ROS and NFATc1 activation.
Pharmacol Res. 2020 09; 159:104944.PR

Abstract

Osteoporosis, characterized by disrupted bone resorption and formation, is viewed as a global health challenge. Arctiin (ARC) is a main component of Arctium lappa L, which exerts chemopreventive effects against various tumor cells. However, the role of ARC in bone remodeling is still unclear. Here, we first demonstrated that ARC inhibits osteoclast formation and bone resorption function induced by the receptor activator of nuclear factor-κB ligand (RANKL) in a dose- and time-dependent manner without exerting cytotoxic effects. Mechanistic analysis revealed that ARC not only suppresses RANKL-induced mitogen-activated protein kinase (MAPK) and calcium signaling pathways, but also enhances the expression of cytoprotective enzymes that are involved in scavenging reactive oxygen species (ROS). Further, ARC inhibits the activation of the major transcription factor nuclear factor of activated T cells 1 (NFATc1) during RANKL-induced osteoclast formation. Preclinical studies showed that ARC protects bone loss in an ovariectomy (OVX) mouse model. Conclusively, our data confirmed that ARC could potentially inhibit osteoclastogenesis by abrogating RANKL-induced MAPK, calcium, and NFATc1 signaling pathway, as well as by promoting the expression of ROS scavenging enzymes in Nrf2/Keap1/ARE signaling pathway, thereby2 preventing OVX-induced bone loss. Thus, ARC may serve as a novel therapeutic agent for the treatment of osteoporosis.

Authors+Show Affiliations

Department of Orthopaedic Surgery, Clifford Hospital, Jinan University, Guangzhou 510006, China; School of Biomedical Sciences, University of Western Australia, Perth, Western Australia 6009, Australia.The First Affiliated Hospital, Wenzhou Medical University, Wenzhou 325000, China.School of Biomedical Sciences, University of Western Australia, Perth, Western Australia 6009, Australia.School of Biomedical Sciences, University of Western Australia, Perth, Western Australia 6009, Australia; Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310000, China.Department of Orthopaedic Surgery, First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou 510405, China.School of Biomedical Sciences, University of Western Australia, Perth, Western Australia 6009, Australia.School of Biomedical Sciences, University of Western Australia, Perth, Western Australia 6009, Australia.School of Biomedical Sciences, University of Western Australia, Perth, Western Australia 6009, Australia.School of Biomedical Sciences, University of Western Australia, Perth, Western Australia 6009, Australia.School of Biomedical Sciences, University of Western Australia, Perth, Western Australia 6009, Australia.The MOE Key Laboratory for Standardization of Chinese Medicines and the SHTCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.School of Biomedical Sciences, University of Western Australia, Perth, Western Australia 6009, Australia; Guangzhou University of Chinese Medicine, Guangzhou 510405, China.School of Biomedical Sciences, University of Western Australia, Perth, Western Australia 6009, Australia; Department of Spine Osteopathy Surgery, First Affiliated Hospital, Guangxi Medical University, Nanning 530021, China.School of Biomedical Sciences, University of Western Australia, Perth, Western Australia 6009, Australia; Guangzhou University of Chinese Medicine, Guangzhou 510405, China.Guangzhou University of Chinese Medicine, Guangzhou 510405, China.Guangzhou University of Chinese Medicine, Guangzhou 510405, China.School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.Department of Orthopaedic Surgery, First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou 510405, China. Electronic address: docchen777@gmail.com.School of Biomedical Sciences, University of Western Australia, Perth, Western Australia 6009, Australia. Electronic address: jiake.xu@uwa.edu.au.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32454224

Citation

Chen, Delong, et al. "Arctiin Abrogates Osteoclastogenesis and Bone Resorption Via Suppressing RANKL-induced ROS and NFATc1 Activation." Pharmacological Research, vol. 159, 2020, p. 104944.
Chen D, Ye Z, Wang C, et al. Arctiin abrogates osteoclastogenesis and bone resorption via suppressing RANKL-induced ROS and NFATc1 activation. Pharmacol Res. 2020;159:104944.
Chen, D., Ye, Z., Wang, C., Wang, Q., Wang, H., Kuek, V., Wang, Z., Qiu, H., Yuan, J., Kenny, J., Yang, F., He, J., Liu, Y., Wang, G., Zhang, M., Zhang, G., Wang, J., Chen, P., & Xu, J. (2020). Arctiin abrogates osteoclastogenesis and bone resorption via suppressing RANKL-induced ROS and NFATc1 activation. Pharmacological Research, 159, 104944. https://doi.org/10.1016/j.phrs.2020.104944
Chen D, et al. Arctiin Abrogates Osteoclastogenesis and Bone Resorption Via Suppressing RANKL-induced ROS and NFATc1 Activation. Pharmacol Res. 2020;159:104944. PubMed PMID: 32454224.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Arctiin abrogates osteoclastogenesis and bone resorption via suppressing RANKL-induced ROS and NFATc1 activation. AU - Chen,Delong, AU - Ye,Zhen, AU - Wang,Chao, AU - Wang,Qingqing, AU - Wang,Haibin, AU - Kuek,Vincent, AU - Wang,Ziyi, AU - Qiu,Heng, AU - Yuan,Jinbo, AU - Kenny,Jacob, AU - Yang,Fan, AU - He,Jianbo, AU - Liu,Yun, AU - Wang,Gang, AU - Zhang,Meng, AU - Zhang,Gangyu, AU - Wang,Junjian, AU - Chen,Peng, AU - Xu,Jiake, Y1 - 2020/05/23/ PY - 2020/03/26/received PY - 2020/05/10/revised PY - 2020/05/15/accepted PY - 2020/5/27/pubmed PY - 2021/7/7/medline PY - 2020/5/27/entrez KW - Arctiin KW - Bone resorption KW - Osteoclast KW - RANKL-induced NFATc1 activation KW - ROS SP - 104944 EP - 104944 JF - Pharmacological research JO - Pharmacol Res VL - 159 N2 - Osteoporosis, characterized by disrupted bone resorption and formation, is viewed as a global health challenge. Arctiin (ARC) is a main component of Arctium lappa L, which exerts chemopreventive effects against various tumor cells. However, the role of ARC in bone remodeling is still unclear. Here, we first demonstrated that ARC inhibits osteoclast formation and bone resorption function induced by the receptor activator of nuclear factor-κB ligand (RANKL) in a dose- and time-dependent manner without exerting cytotoxic effects. Mechanistic analysis revealed that ARC not only suppresses RANKL-induced mitogen-activated protein kinase (MAPK) and calcium signaling pathways, but also enhances the expression of cytoprotective enzymes that are involved in scavenging reactive oxygen species (ROS). Further, ARC inhibits the activation of the major transcription factor nuclear factor of activated T cells 1 (NFATc1) during RANKL-induced osteoclast formation. Preclinical studies showed that ARC protects bone loss in an ovariectomy (OVX) mouse model. Conclusively, our data confirmed that ARC could potentially inhibit osteoclastogenesis by abrogating RANKL-induced MAPK, calcium, and NFATc1 signaling pathway, as well as by promoting the expression of ROS scavenging enzymes in Nrf2/Keap1/ARE signaling pathway, thereby2 preventing OVX-induced bone loss. Thus, ARC may serve as a novel therapeutic agent for the treatment of osteoporosis. SN - 1096-1186 UR - https://www.unboundmedicine.com/medline/citation/32454224/Arctiin_abrogates_osteoclastogenesis_and_bone_resorption_via_suppressing_RANKL_induced_ROS_and_NFATc1_activation_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1043-6618(20)31252-4 DB - PRIME DP - Unbound Medicine ER -