Morin attenuates osteoclast formation and function by suppressing the NF-κB, MAPK and calcium signalling pathways.
Yifeng ShiLin YeShiwei ShenTianchen QianYoujin PanYuhan JiangJinghao LinChen LiuYaosen WuXiangyang WangJiake XuHaiming JinPublished in: Phytotherapy research : PTR (2021)
Morin is a natural compound isolated from moraceae family members and has been reported to possess a range of pharmacological activities. However, the effects of morin on bone-associated disorders and the potential mechanism remain unknown. In this study, we investigated the anti-osteoclastogenic effect of morin in vitro and the potential therapeutic effects on ovariectomy (OVX)-induced osteoporosis in vivo. In vitro, by using a bone marrow macrophage-derived osteoclast culture system, we determined that morin attenuated receptor activator of nuclear factor (NF)-κB ligand (RANKL)-induced osteoclast formation via the inhibition of the mitogen-activated protein kinase (MAPK), NF-κB and calcium pathways. In addition, the subsequent expression of nuclear factor of activated T cells c1 (NFATc1) and c-fos was significantly suppressed by morin. In addition, NFATc1 downregulation led to the reduced expression of osteoclastogenesis-related marker genes, such as V-ATPase-d2 and Integrin β3. In vivo, results provided that morin could effectively attenuate OVX-induced bone loss in C57BL/6 mice. In conclusion, our results demonstrated that morin suppressed RANKL-induced osteoclastogenesis via the NF-κB, MAPK and calcium pathways, in addition, its function of preventing OVX-induced bone loss in vivo, which suggested that morin may be a potential therapeutic agent for postmenopausal osteoporosis treatment.
Keyphrases
- bone loss
- nuclear factor
- signaling pathway
- toll like receptor
- high glucose
- diabetic rats
- oxidative stress
- bone marrow
- pi k akt
- lps induced
- drug induced
- poor prognosis
- bone mineral density
- postmenopausal women
- high resolution
- adipose tissue
- cell proliferation
- immune response
- gene expression
- long non coding rna
- tyrosine kinase
- metabolic syndrome
- endothelial cells
- mass spectrometry
- body composition
- protein kinase
- insulin resistance
- high fat diet induced
- bioinformatics analysis