期刊
EUROPEAN JOURNAL OF PHARMACOLOGY
卷 921, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.ejphar.2022.174865
关键词
Urolithin A; Osteoclastogenesis; Oxidative stress; MAPK; Nrf2
资金
- Funding Project of National Old Traditional Chinese Medicine Experts Academic Experience Inheritance Work in 2017 [29]
Urolithin A can attenuate RANKL-induced osteoclastogenesis by suppressing inflammation and activating the Nrf2 signaling pathway, thereby alleviating bone loss.
As a critical regulator of bone resorption. osteoclastogenesis is closely associated with osteoporosis (OP) and commonly induced by receptor activator of nuclear factor -kappa B ligand (RANKL), suggesting that suppression of inflammation may improve OP. Urolithin A (UroA), an active metabolite of ellagic acid, is known to exert antiinflammatory and antioxidative effects. However, whether UroA attenuates osteoclastogenesis remains unclear. Using a lipopolysaccharide (LPS)-induced bone loss model, we evaluated the effects of UroA on inflammatory osteoclastogenesis in mice and explored the potential mechanism from RANKL-related signaling pathway. UroA significantly improved LPS-induced bone loss and rescued the imbalance in bone microarchitecture parameters. Hematoxylin & eosin (H & E) and tartrate resistant acid phosphatase (TRAP) staining of femurs showed that UroA suppressed LPS-induced osteoclastogenesis accompanied by the activation of nuclear factor-erythroid 2-related factor 2 (Nrf2) signaling. In RANKL-triggered mouse bone marrow-derived macrophages (BMDMs), UroA inhibited the formation of osteoclasts and Fibrous actin rings (F-actin rings), and decreased TRAP activity. Moreover, UroA significantly decreased mRNA and protein expression of major inflammatory cytokines in LPSchallenged RAW264.7 cells by decreasing the phosphorylation of NF -kappa B p65, c-Jun N-terminal kinase (JNK), extracellular signal regulated kinase1/2 (Erk1/2), and p38. Furthermore, UroA may activate the Nrf2 signaling pathway by increasing mRNA and protein expression of antioxidant proteins. We conclude that UroA attenuated RANKL-induced osteoclastogenesis by suppressing the p38 mitogen-activated protein kinase (MAPK) pathway and inducing Nrf2 nuclear translocation. Thus, supplementation with UroA may help alleviate inflammation induced bone loss and bone resorption.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据