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Maslinic acid suppresses osteoclastogenesis and prevents ovariectomy-induced bone loss by regulating RANKL-mediated NF-κB and MAPK signaling pathways.
J Bone Miner Res. 2011 Mar; 26(3):644-56.JB

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.

Authors+Show Affiliations

Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

20814972

Citation

Li, Chenghai, et al. "Maslinic Acid Suppresses Osteoclastogenesis and Prevents Ovariectomy-induced Bone Loss By Regulating RANKL-mediated NF-κB and MAPK Signaling Pathways." Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research, vol. 26, no. 3, 2011, pp. 644-56.
Li C, Yang Z, Li Z, et al. Maslinic acid suppresses osteoclastogenesis and prevents ovariectomy-induced bone loss by regulating RANKL-mediated NF-κB and MAPK signaling pathways. J Bone Miner Res. 2011;26(3):644-56.
Li, C., Yang, Z., Li, Z., Ma, Y., Zhang, L., Zheng, C., Qiu, W., Wu, X., Wang, X., Li, H., Tang, J., Qian, M., Li, D., Wang, P., Luo, J., & Liu, M. (2011). Maslinic acid suppresses osteoclastogenesis and prevents ovariectomy-induced bone loss by regulating RANKL-mediated NF-κB and MAPK signaling pathways. Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research, 26(3), 644-56. https://doi.org/10.1002/jbmr.242
Li C, et al. Maslinic Acid Suppresses Osteoclastogenesis and Prevents Ovariectomy-induced Bone Loss By Regulating RANKL-mediated NF-κB and MAPK Signaling Pathways. J Bone Miner Res. 2011;26(3):644-56. PubMed PMID: 20814972.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Maslinic acid suppresses osteoclastogenesis and prevents ovariectomy-induced bone loss by regulating RANKL-mediated NF-κB and MAPK signaling pathways. AU - Li,Chenghai, AU - Yang,Zhengfeng, AU - Li,Zhenxi, AU - Ma,Yu, AU - Zhang,Lipeng, AU - Zheng,Chunbing, AU - Qiu,Wenwei, AU - Wu,Xian, AU - Wang,Xiu, AU - Li,Hui, AU - Tang,Jie, AU - Qian,Min, AU - Li,Dali, AU - Wang,Ping, AU - Luo,Jian, AU - Liu,Mingyao, PY - 2010/9/4/entrez PY - 2010/9/4/pubmed PY - 2011/5/26/medline SP - 644 EP - 56 JF - Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research JO - J. Bone Miner. Res. VL - 26 IS - 3 N2 - 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. SN - 1523-4681 UR - https://www.unboundmedicine.com/medline/citation/20814972/Maslinic_acid_suppresses_osteoclastogenesis_and_prevents_ovariectomy_induced_bone_loss_by_regulating_RANKL_mediated_NF_κB_and_MAPK_signaling_pathways_ L2 - https://doi.org/10.1002/jbmr.242 DB - PRIME DP - Unbound Medicine ER -