Cytisine attenuates bone loss of ovariectomy mouse by preventing RANKL‐induced osteoclastogenesis
| Autor: | Jun Qian, Ying Zhou, Dejian Li, Baoqing Yu, Fangxue Zhang, Zhanrong Kang, Zeyuan Zhong, Zhi Qian, Shuo Ni |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty SC79 Ovariectomy cytisine Osteoclasts Bone resorption 03 medical and health sciences Cytisine chemistry.chemical_compound Mice Phosphatidylinositol 3-Kinases 0302 clinical medicine Alkaloids Osteoclast Osteogenesis Internal medicine Cathepsin K medicine Animals Bone Resorption Protein kinase B osteoclastogenesis biology NF‐κB RANK Ligand AKT‐NFATc1 NF-kappa B Cell Biology Original Articles MAPK Azocines Mice Inbred C57BL IκBα 030104 developmental biology Endocrinology medicine.anatomical_structure RAW 264.7 Cells chemistry RANKL 030220 oncology & carcinogenesis Ovariectomized rat biology.protein Molecular Medicine Original Article Female Proto-Oncogene Proteins c-akt Quinolizines Signal Transduction |
| Zdroj: | Journal of Cellular and Molecular Medicine |
| ISSN: | 1582-4934 1582-1838 |
| Popis: | Postmenopausal Osteoporosis (PMOP) is oestrogen withdrawal characterized of much production and activation by osteoclast in the elderly female. Cytisine is a quinolizidine alkaloid that comes from seeds or other plants of the Leguminosae (Fabaceae) family. Cytisine has been shown several potential pharmacological functions. However, its effects on PMOP remain unknown. This study designed to explore whether Cytisine is able to suppress RANKL‐induced osteoclastogenesis and prevent the bone loss induced by oestrogen deficiency in ovariectomized (OVX) mice. In this study, we investigated the effect of Cytisine on RAW 264.7 cells and bone marrow monocytes (BMMs) derived osteoclast culture system in vitro and observed the effect of Cytisine on ovariectomized (OVX) mice model to imitate postmenopausal osteoporosis in vivo. We found that Cytisine inhibited F‐actin ring formation and tartrate‐resistant acid phosphatase (TRAP) staining in dose‐dependent ways, as well as bone resorption by pit formation assays. For molecular mechanism, Cytisine suppressed RANK‐related trigger RANKL by phosphorylation JNK/ERK/p38‐MAPK, IκBα/p65‐NF‐κB, and PI3K/AKT axis and significantly inhibited these signalling pathways. However, the suppression of PI3K‐AKT‐NFATc1 axis was rescued by AKT activator SC79. Meanwhile, Cytisine inhibited RANKL‐induced RANK‐TRAF6 association and RANKL‐related gene and protein markers such as NFATc1, Cathepsin K, MMP‐9 and TRAP. Our study indicated that Cytisine could suppress bone loss in OVX mouse through inhibited osteoclastogenesis. All data provide the evidence that Cytisine may be a promising agent in the treatment of osteoclast‐related diseases such as osteoporosis. |
| Databáze: | OpenAIRE |
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