Received: 16 December 2017 | Accepted: 17 July 2018 DOI: 10.1002/jcp.27195 ORIGINAL RESEARCH ARTICLE Asiaticoside, a component of Centella asiatica attenuates RANKL‐induced osteoclastogenesis via NFATc1 and NF‐κB signaling pathways Lilei He 1,2 * | Guoju Hong 3,4,5 * | Lin Zhou 6 | Jianguo Zhang 2 | Jian Fang 2 | Wei He 3 | Jennifer Tickner 4 | Xiaorui Han 7 | Lilian Zhao 2 | Jiake Xu 3,4 1 Department of Orthopaedics, Affiliated Foshan Hospital, Guangzhou University of Traditional Chinese Medicine, Guangzhou, Guangdong, China 2 The Third Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, Guangzhou, Guangdong, China 3 National Key Discipline and Orthopedic Laboratory, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China 4 School of Biomedical Sciences, The University of Western Australia, Perth, Western Australia, Australia 5 Orthopedic Department, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China 6 Department of Rheumatology, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China 7 Department of Radiography, Guangzhou First People's Hospital, The Second Affiliated Hospital of South China University of Technology, Guangzhou, Guangdong, China Correspondence Dr. Xiaorui Han, Department of Radiography, Guangzhou First People's Hospital, The Second Affiliated Hospital of South China University of Technology, Guangzhou, Guangdong, China. Email: sxllhxr@yahoo.com Prof. Lilian Zhao, Department of Orthopaedics, Affiliated Foshan Hospital, Guangzhou University of Traditional Chinese Medicine, 6 Qinren Road, Foshan, Guangdong, China. Email: zhaolilian@163.com Prof. Jiake Xu, School of Biomedical Sciences, The University of Western Australia M508, 35 Stirling Hwy, Perth, WA 6009, Australia. Email: jiake.xu@uwa.edu.au Funding information Guangdong Medical Science and Technology Research Foundation, Grant/Award Number: A2016580; Australian Health and Medical Research Council, Grant/Award Numbers: APP1127396, APP1107828, APP1127156; National Natural Science Foundation of China, Grant/Award Numbers: 81573996, 81473697 Identification of natural compounds that inhibit osteoclastogenesis will facilitate the development of antiresorptive treatment of osteolytic bone diseases. Asiaticoside is a triterpenoid derivative isolated from Centella asiatica, which exhibits varying biological effects like angiogenesis, anti‐inflammation, wound healing, and osteogenic differentiation. However, its role in osteoclastogenesis remains unknown. Here, we show that Asiaticoside can suppress RANKL‐induced osteoclast formation and bone resorption in a dose‐dependent manner. Asiaticoside attenuated the expression of osteoclast marker genes including Ctsk, Atp6v0d2, Nfatc1, Acp5, and Dc-stamp. Furthermore, Asiaticoside inhibited RANKL‐mediated NF‐κB and NFATc1 activities, and RANKL‐induced calcium oscillation. Collectively, this study demonstrates that Asiaticoside inhibited osteoclast formation and function through attenuating RANKL‐ induced key signaling pathways, which may indicate that Asiaticoside is a potential antiresorptive agent against osteoclast‐related osteolytic bone diseases. KEYWORDS asiaticoside, NF‐κB, NFAT pathway, osteoclast, RANKL 1 | INTRODUCTION Bone homeostasis is a balanced process involving the coupling of bone formation by osteoblasts and bone resorption by osteoclasts (Katsimbri, 2017; Sims & Ng, 2014; Zhu et al., 2017). Disruption of coupling processes due to the over activation of osteoclasts can lead to osteolytic bone conditions like osteoporosis and osteonecrosis (Chen et al., 2017; Kelleher & O’Sullivan, 2017; Kerachian, Seguin, & Harvey, 2009), resulting in skeletal weakness and low impact fractures (Gerdhem, 2013). Existing treatments for suppressing osteoclast formation and enhancing osteoblast differentiation are still limited (Tella & Gallagher, 2014; Weinstein, 2012) with various unwanted side effects (Ishtiaq, Fogelman, & Hampson, 2015; Thirunavukarasu, Pinto, & Seymour, 2015), so the exploration and J Cell Physiol. 2018;1–10. wileyonlinelibrary.com/journal/jcp © 2018 Wiley Periodicals, Inc. | 1 *Lilei He and Guoju Hong contributed equally to this work.