期刊
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
卷 23, 期 1, 页码 380-394出版社
WILEY
DOI: 10.1111/jcmm.13942
关键词
MAPK; NFATc1; NF-kappa B; Osteoclast; OVX
资金
- Natural Science Foundation of Guangxi Province [2015GXNSFDA139019]
- National Natural Science Foundation of China [81572227]
- Australian Health and Medical Research Council [11027932, 1107828]
- Western Australia Medical & Health Research Infrastructure Fund
- Arthritis Australia Foundation
- University of Western Australia (UWA) Research Collaboration Awards
- National Health and Medical Research Council of Australia [1107828] Funding Source: NHMRC
Osteoporosis is the most common osteolytic disease characterized by excessive osteoclast formation and resultant bone loss, which afflicts millions of patients around the world. Madecassoside (MA), isolated from Centella asiatica, was reported to have anti-inflammatory and antioxidant activities, but its role in osteoporosis treatment has not yet been confirmed. In our study, MA was found to have an inhibitory effect on the RANKL-induced formation and function of OCs in a dose-dependent manner without cytotoxicity. These effects were attributed to its ability to suppress the activity of two transcription factors (NFATc1 and c-Fos) indispensable for osteoclast formation, followed by inhibition of the expression of bone resorption-related genes and proteins (Acp5/TRAcP, CTSK, ATP6V0D2/V-ATPase-d2, and integrin beta 3). Furthermore, we examined the underlying mechanisms and found that MA represses osteoclastogenesis by blocking Ca2+ oscillations and the NF-kappa B and MAPK pathways. In addition, the therapeutic effect of MA on preventing bone loss in vivo was further confirmed in an ovariectomized mouse model. Therefore, considering its ability to inhibit RANKL-mediated osteoclastogenesis and the underlying mechanisms, MA might be a potential candidate for treating osteolytic bone diseases.
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