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- Title
Maslinic acid suppresses osteoclastogenesis and prevents ovariectomy-induced bone loss by regulating RANKL-mediated NF-κB and MAPK signaling pathways.
- Authors
Chenghai Li; Zhengfeng Yang; Zhenxi Li; Yu Ma; Lipeng Zhang; Chunbing Zheng; Wenwei Qiu; Xian Wu; Xiu Wang; Hui Li; Jie Tang; Min Qian; Dali Li; Ping Wang; Jian Luo; Mingyao Liu
- Abstract
Activation of NF-κB and MAPK/activator protein 1 (AP-1) signaling pathways by receptor activator NF-κB ligand (RANKL) is essential for osteoclast activity. Targeting NF-κB and MAPK/AP-1 signaling to modulate osteoclast activity has been a promising strategy for osteoclast-related diseases. In this study we examined the effects of maslinic acid (MA), a pentacyclic triterpene acid that is widely present in dietary plants, on RANKL-induced osteoclastogenesis, osteoclast function, and signaling pathways by in vitro and in vivo assay systems. In mouse bone marrow monocytes (BMMs) and RAW264.7 cells, MA inhibited RANKL-induced osteoclastogenesis in a dose-dependent manner within nongrowth inhibitory concentration, and MA decreased osteoclastogenesis-related marker gene expression, including TRACP, MMP9, c-Src, CTR, and cathepsin K. Specifically, MA suppressed osteoclastogenesis and actin ring formation at early stage. In ovariectomized mice, administration of MA prevented ovariectomy-induced bone loss by inhibiting osteoclast activity. At molecular levels, MA abrogated the phosphorylation of MAPKs and AP-1 activity, inhibited the IκBα phosphorylation and degradation, blocked NF-κB/p65 phosphorylation, nuclear translocation, and DNA-binding activity by downregulating RANK expression and blocking RANK interaction with TRAF6. Together our data demonstrate that MA suppresses RANKL-induced osteoclastogenesis through NF-κB and MAPK/AP-1 signaling pathways and that MA is a promising agent in the treatment of osteoclast-related diseases such as osteoporosis. © 2011 American Society for Bone and Mineral Research.
- Subjects
OSTEOCLASTS; PROTEIN research; LIGANDS (Biochemistry); MITOGEN-activated protein kinases; GENE expression; OSTEOPOROSIS
- Publication
Journal of Bone & Mineral Research, 2011, Vol 26, Issue 3, p644
- ISSN
0884-0431
- Publication type
Article
- DOI
10.1002/jbmr.242