Tomatidine suppresses osteoclastogenesis and mitigates estrogen deficiency-induced bone mass loss by modulating TRAF6-mediated signaling
| Autor: | Chenhe Zhou, Zhi-Min Ying, Shigui Yan, Sihao Li, Yute Yang, Jiahong Meng, Fengfeng Wu, Bin Hu, Han-Xiao Zhu, Guangyao Jiang, Xiang Zhao, Zhongli Shi, Haobo Wu, Xun-Zi Cai, Xuewu Sun |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
p38 mitogen-activated protein kinases Ovariectomy Osteoclasts Biochemistry Bone resorption 03 medical and health sciences Tomatine 0302 clinical medicine Osteoclast Osteogenesis Genetics medicine Animals Humans Bone Resorption Receptor Molecular Biology Protein kinase B Cells Cultured TNF Receptor-Associated Factor 6 Chemistry Kinase Activator (genetics) NF-kappa B Cell Differentiation Estrogens Cell biology Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure Gene Expression Regulation Phosphorylation Female 030217 neurology & neurosurgery Biotechnology Signal Transduction |
| Zdroj: | FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 33(2) |
| ISSN: | 1530-6860 |
| Popis: | Postmenopausal osteoporosis is initiated by estrogen withdrawal and is characterized mainly by overactivated osteoclastic bone resorption. Targeting TNF receptor-associated factor 6 (TRAF6) or its downstream signaling pathways to modulate osteoclast formation and function is an appealing strategy for osteoclast-related disorders. In the present study, we determined the effect of tomatidine, a steroidal alkaloid derived from Solanaceae, on the formation and function of receptor activator of NF-κB (RANK) ligand-induced osteoclasts and the underlying mechanism. Tomatidine inhibited osteoclast formation in a dose-dependent manner and decreased the expression of osteoclast marker genes. Actin ring formation and osteoclastic bone resorption were attenuated in the presence of tomatidine in vitro. Eight weeks after ovariectomy, tomatidine prevented estrogen deficiency-induced bone loss and restored the mechanical properties of the femur. At the molecular level, tomatidine abrogated phosphorylation of c-Jun N-terminal kinase (JNK)/p38, NF-κB, and protein kinase B (Akt) pathway proteins by suppressing RANK expression, inhibiting the binding of TRAF6 to RANK, and downregulating the osteoclastogenesis marker-related protein expression. In summary, these data demonstrated that tomatidine attenuated osteoclast formation and function by modulating multiple TRAF6-mediated pathways. Therefore, tomatidine could be a novel candidate for the treatment of osteoclast-related disorders, including osteoporosis.-Hu, B., Sun, X., Yang, Y., Ying, Z., Meng, J., Zhou, C., Jiang, G., Li, S., Wu, F., Zhao, X., Zhu, H., Wu, H., Cai, X., Shi, Z., Yan, S. Tomatidine suppresses osteoclastogenesis and mitigates estrogen deficiency-induced bone mass loss by modulating TRAF6-mediated signaling. |
| Databáze: | OpenAIRE |
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