Dencichine prevents ovariectomy-induced bone loss and inhibits osteoclastogenesis by inhibiting RANKL-associated NF-κB and MAPK signaling pathways
| Autor: | Ya Wu, Xiaofei Shen, Feng Li, Biao Ji, Chi Yang, Guoyou Zou, Dingwei Cang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
MAPK/ERK pathway Osteoclastogenesis MAP Kinase Signaling System Ovariectomy p38 mitogen-activated protein kinases RM1-950 Bone resorption NF-κB Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Western blot Osteogenesis Cathepsin K medicine Animals Humans Osteoporosis Postmenopausal Pharmacology biology medicine.diagnostic_test Signaling pathway RANK Ligand NF-kappa B Amino Acids Diamino Dencichine MAPK Cell biology Mice Inbred C57BL RAW 264.7 Cells 030104 developmental biology chemistry RANKL biology.protein Molecular Medicine Female Therapeutics. Pharmacology Signal transduction 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | Journal of Pharmacological Sciences, Vol 146, Iss 4, Pp 206-215 (2021) |
| ISSN: | 1347-8613 |
| Popis: | Aims To investigate the effect of dencichine on osteoclastogenesis in vivo and in vitro. Methods RANKL-induced osteoclastogenesis were treated with different concentrations of dencichine. Pit forming assays were applied to evaluate the degree of bone resorption. Osteoclastogenic markers were detected by real-time quantitative PCR (RT-qPCR) and Western blot. Micro CT was conducted to investigate the effects of dencichine on osteoclastogenesis in ovariectomized (OVX) mice. Results Dencichine suppressed osteoclastogenesis through the inhibition of phosphorylation of p65, p50 (NF-κB pathway), p38, ERK and JNK (MAPKs pathway) in vitro. Furthermore, dencichine inhibited the function of osteoclasts in a dose-dependent manner. In addition, the expression levels of the nuclear factor of activated T cells 1 (NFATc1) and osteoclastogenesis markers were decreased by dencichine, including MMP-9, Cathepsin K (CTSK), Tartrate-Resistant Acid Phosphatase (TRAP), C-FOS, dendritic cell specific transmembrane protein (DC-STAMP). In vivo data proved that dencichine alleviated ovariectomy-induced bone loss and osteoclastogenesis in mice. Conclusion Our results demonstrate that dencichine alleviates OVX-induced bone loss in mice and inhibits RANKL-mediated osteoclastogenesis via inhibition of NF-κB and MAPK pathways in vitro, suggesting that dencichine might serve as a promising candidate for treatment of bone loss diseases, including PMOP and rheumatoid arthritis. |
| Databáze: | OpenAIRE |
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