Tags

Type your tag names separated by a space and hit enter

Caffeic acid 3,4-dihydroxy-phenethyl ester suppresses receptor activator of NF-κB ligand–induced osteoclastogenesis and prevents ovariectomy-induced bone loss through inhibition of mitogen-activated protein kinase/activator protein 1 and Ca2+–nuclear factor of activated T-cells cytoplasmic 1 signaling pathways.
J Bone Miner Res. 2012 Jun; 27(6):1298-1308.JB

Abstract

Receptor activator of NF-κB ligand (RANKL) stimulation leads to the activation of mitogen-activated protein kinase (MAPK)/AP-1 and Ca2+–nuclear factor of activated T-cells cytoplasmic 1 (NFATc1) signaling pathways in osteoclastogenesis. Targeting these pathways has been an encouraging strategy for bone-related diseases, such as postmenopausal osteoporosis. In this study, we examined the effects of caffeic acid 3,4-dihydroxy-phenethyl ester (CADPE) on osteoclastogenesis. In mouse bone marrow monocytes (BMMs) and RAW264.7 cells, CADPE suppressed RANKL-induced osteoclast differentiation and actin-ring formation in a dose-dependent manner within non–growth inhibitory concentrations at the early stage, while CADPE had no effect on macrophage colony-stimulating factor (M-CSF)-induced proliferation and differentiation. At the molecular level, CADPE inhibited RANKL-induced phosphorylation of MAPKs, including extracellular signal-regulated kinases 1/2 (ERK1/2), p38, and c-Jun N-terminal kinase (JNK), without significantly affecting the NF-κB signaling pathway. CADPE abrogated RANKL-induced activator protein 1 (AP-1)/FBJ murine osteosarcoma viral oncogene homolog (c-Fos) nuclear translocation and activation. Overexpression of c-Fos prevented the inhibition by CADPE of osteoclast differentiation. Furthermore, CADPE suppressed RANKL-induced the tumor necrosis factor receptor associated factor 6 (TRAF6) interaction with c-src tyrosine kinase (c-Src), blocked RANKL-induced the phosphorylation of protein kinase B (AKT), and inhibited RANKL-induced Ca2+ oscillation. As a result, CADPE decreased osteoclastogenesis-related marker gene expression, including NFATc1, TRAP, cathepsin K, and c-Src. To test the effects of CADPE on osteoclast activity in vivo, we showed that CADPE prevented ovariectomy-induced bone loss by inhibiting osteoclast activity. Together, our data demonstrate that CADPE suppresses osteoclastogenesis and bone loss through inhibiting RANKL-induced MAPKs and Ca2+-NFATc1 signaling pathways. CADPE is a novel agent in the treatment of osteoclast-related diseases, such as osteoporosis.

Authors+Show Affiliations

Shanghai Key Laboratory of Regulatory Biology, 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 available

Pub Type(s)

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

Language

eng

PubMed ID

22337253

Citation

Wu, Xian, et al. "Caffeic Acid 3,4-dihydroxy-phenethyl Ester Suppresses Receptor Activator of NF-κB Ligand–induced Osteoclastogenesis and Prevents Ovariectomy-induced Bone Loss Through Inhibition of Mitogen-activated Protein Kinase/activator Protein 1 and Ca2+–nuclear Factor of Activated T-cells Cytoplasmic 1 Signaling Pathways." Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research, vol. 27, no. 6, 2012, pp. 1298-1308.
Wu X, Li Z, Yang Z, et al. Caffeic acid 3,4-dihydroxy-phenethyl ester suppresses receptor activator of NF-κB ligand–induced osteoclastogenesis and prevents ovariectomy-induced bone loss through inhibition of mitogen-activated protein kinase/activator protein 1 and Ca2+–nuclear factor of activated T-cells cytoplasmic 1 signaling pathways. J Bone Miner Res. 2012;27(6):1298-1308.
Wu, X., Li, Z., Yang, Z., Zheng, C., Jing, J., Chen, Y., Ye, X., Lian, X., Qiu, W., Yang, F., Tang, J., Xiao, J., Liu, M., & Luo, J. (2012). Caffeic acid 3,4-dihydroxy-phenethyl ester suppresses receptor activator of NF-κB ligand–induced osteoclastogenesis and prevents ovariectomy-induced bone loss through inhibition of mitogen-activated protein kinase/activator protein 1 and Ca2+–nuclear factor of activated T-cells cytoplasmic 1 signaling pathways. Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research, 27(6), 1298-1308. https://doi.org/10.1002/jbmr.1576
Wu X, et al. Caffeic Acid 3,4-dihydroxy-phenethyl Ester Suppresses Receptor Activator of NF-κB Ligand–induced Osteoclastogenesis and Prevents Ovariectomy-induced Bone Loss Through Inhibition of Mitogen-activated Protein Kinase/activator Protein 1 and Ca2+–nuclear Factor of Activated T-cells Cytoplasmic 1 Signaling Pathways. J Bone Miner Res. 2012;27(6):1298-1308. PubMed PMID: 22337253.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Caffeic acid 3,4-dihydroxy-phenethyl ester suppresses receptor activator of NF-κB ligand–induced osteoclastogenesis and prevents ovariectomy-induced bone loss through inhibition of mitogen-activated protein kinase/activator protein 1 and Ca2+–nuclear factor of activated T-cells cytoplasmic 1 signaling pathways. AU - Wu,Xian, AU - Li,Zhenxi, AU - Yang,Zhengfang, AU - Zheng,Chunbing, AU - Jing,Ji, AU - Chen,Yihua, AU - Ye,Xiyun, AU - Lian,Xiaoyuan, AU - Qiu,Wenwei, AU - Yang,Fan, AU - Tang,Jie, AU - Xiao,Jianru, AU - Liu,Mingyao, AU - Luo,Jian, PY - 2012/2/17/entrez PY - 2012/2/18/pubmed PY - 2012/9/14/medline SP - 1298 EP - 1308 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 - 27 IS - 6 N2 - Receptor activator of NF-κB ligand (RANKL) stimulation leads to the activation of mitogen-activated protein kinase (MAPK)/AP-1 and Ca2+–nuclear factor of activated T-cells cytoplasmic 1 (NFATc1) signaling pathways in osteoclastogenesis. Targeting these pathways has been an encouraging strategy for bone-related diseases, such as postmenopausal osteoporosis. In this study, we examined the effects of caffeic acid 3,4-dihydroxy-phenethyl ester (CADPE) on osteoclastogenesis. In mouse bone marrow monocytes (BMMs) and RAW264.7 cells, CADPE suppressed RANKL-induced osteoclast differentiation and actin-ring formation in a dose-dependent manner within non–growth inhibitory concentrations at the early stage, while CADPE had no effect on macrophage colony-stimulating factor (M-CSF)-induced proliferation and differentiation. At the molecular level, CADPE inhibited RANKL-induced phosphorylation of MAPKs, including extracellular signal-regulated kinases 1/2 (ERK1/2), p38, and c-Jun N-terminal kinase (JNK), without significantly affecting the NF-κB signaling pathway. CADPE abrogated RANKL-induced activator protein 1 (AP-1)/FBJ murine osteosarcoma viral oncogene homolog (c-Fos) nuclear translocation and activation. Overexpression of c-Fos prevented the inhibition by CADPE of osteoclast differentiation. Furthermore, CADPE suppressed RANKL-induced the tumor necrosis factor receptor associated factor 6 (TRAF6) interaction with c-src tyrosine kinase (c-Src), blocked RANKL-induced the phosphorylation of protein kinase B (AKT), and inhibited RANKL-induced Ca2+ oscillation. As a result, CADPE decreased osteoclastogenesis-related marker gene expression, including NFATc1, TRAP, cathepsin K, and c-Src. To test the effects of CADPE on osteoclast activity in vivo, we showed that CADPE prevented ovariectomy-induced bone loss by inhibiting osteoclast activity. Together, our data demonstrate that CADPE suppresses osteoclastogenesis and bone loss through inhibiting RANKL-induced MAPKs and Ca2+-NFATc1 signaling pathways. CADPE is a novel agent in the treatment of osteoclast-related diseases, such as osteoporosis. SN - 1523-4681 UR - https://www.unboundmedicine.com/medline/citation/22337253/Caffeic_acid_34_dihydroxy_phenethyl_ester_suppresses_receptor_activator_of_NF_κB_ligand–induced_osteoclastogenesis_and_prevents_ovariectomy_induced_bone_loss_through_inhibition_of_mitogen_activated_protein_kinase/activator_protein_1_and_Ca2+–nuclear_factor_of_activated_T_cells_cytoplasmic_1_signaling_pathways_ L2 - https://doi.org/10.1002/jbmr.1576 DB - PRIME DP - Unbound Medicine ER -