Details

Autor(en) / Beteiligte

• Kwak, Sung Chul
• Baek, Jong Min
• Lee, Chang Hoon
• Yoon, Kwon-Ha
• Lee, Myeung Su
• Kim, Ju-Young

Titel

Umbelliferone Prevents Lipopolysaccharide-Induced Bone Loss and Suppresses RANKL-Induced Osteoclastogenesis by Attenuating Akt-c-Fos-NFATc1 Signaling

Ist Teil von

• International journal of biological sciences, 2019-01, Vol.15 (11), p.2427-2437

Ort / Verlag

Australia: Ivyspring International Publisher Pty Ltd

Erscheinungsjahr

2019

Quelle

MEDLINE

Beschreibungen/Notizen

• Excessive bone resorption plays a central role in the development of inflammatory bone diseases, including osteoporosis and rheumatoid arthritis. Thus, identification of agents that can effectively suppress excessive osteoclast formation and function is crucial for the prevention and treatment of inflammatory bone loss. Umbelliferone (Umb), a derivative of coumarin, is a natural bioactive compound with anti-inflammatory and antioxidant properties. However, the effect of Umb on metabolic bone diseases is unknown. In this study, we found that Umb exhibited a strong inhibitory effect on lipopolysaccharide (LPS)-induced inflammatory bone loss . Histological analysis confirmed that Umb prevented trabecular bone matrix degradation and osteoclast formation in bone tissue. In addition, Umb suppressed RANKL-induced osteoclast differentiation and abrogated bone resorption. We found that the anti-osteoclastic and anti-resorptive activities of Umb are mediated suppression of the RANKL-induced Akt-c-Fos-NFATc1 signaling pathway and the attenuation of osteoclast-specific genes, such as , , , and . In particular, Umb downregulated the stability of c-Fos and NFATc1 proteins, but did not suppress the expression of their mRNAs. These results indicate that Umb may be a potential therapeutic agent for inflammatory bone diseases associated with abnormal osteoclast formation and function.