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.

Links

Publisher Full Text

Authors+Show Affiliations

Wu X
Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
Li Z
No affiliation info available
Yang Z
No affiliation info available
Zheng C
No affiliation info available
Jing J
No affiliation info available
Chen Y
No affiliation info available
Ye X
No affiliation info available
Lian X
No affiliation info available
Qiu W
No affiliation info available
Yang F
No affiliation info available
Tang J
No affiliation info available
Xiao J
No affiliation info available
Liu M
No affiliation info available
Luo J
No affiliation info available

MeSH

ActinsAnimalsBiomarkersBone Marrow CellsBone ResorptionCaffeic AcidsCalciumCalcium SignalingCell DifferentiationCell LineCell ProliferationFemaleGene Expression RegulationMacrophage Colony-Stimulating FactorMacrophagesMiceMitogen-Activated Protein KinasesNF-kappa BNFATC Transcription FactorsOsteoblastsOsteoclastsOsteogenesisOvariectomyRANK LigandTranscription Factor AP-1

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 -