Details

Autor(en) / Beteiligte

• Wei, Wei
• Peng, Chenjian
• Gu, Renjun
• Yan, Xiwu
• Ye, Jiapeng
• Xu, Zhuicheng
• Sheng, Xianjie
• Huang, Guicheng
• Guo, Yang

Titel

Urolithin A attenuates RANKL-induced osteoclastogenesis by co-regulating the p38 MAPK and Nrf2 signaling pathway

Ist Teil von

• European journal of pharmacology, 2022-04, Vol.921, p.174865-174865, Article 174865

Ort / Verlag

Netherlands: Elsevier B.V

Erscheinungsjahr

2022

Quelle

ScienceDirect

Beschreibungen/Notizen

• As a critical regulator of bone resorption. osteoclastogenesis is closely associated with osteoporosis (OP) and commonly induced by receptor activator of nuclear factor-κB ligand (RANKL), suggesting that suppression of inflammation may improve OP. Urolithin A (UroA), an active metabolite of ellagic acid, is known to exert anti-inflammatory 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 LPS-challenged RAW264.7 cells by decreasing the phosphorylation of NF-κB 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.