AB0094 Genipin Inhibits Rankl-Induced Osteoclast Differentiation Through. (10th June 2014)

• Record Type: Journal Article
• Authors: Lee, C.-H.; Kim, J.-Y.; Oh, J.-M.; Yoo, W.-H.; Beak, S.-H.; Choi, J.-J.; Lee, W.-S.; Lee, M.-S.
• Is Part Of: Annals of the rheumatic diseases. Volume 73:Supplement 2(2014)
• Page Start: 835
• Page End: 835
• Publication Date: 2014-06-10
• Subjects: Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2014-eular.2308
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : Background: People over the age of 50 are at risk of osteoporotic fracture, which may lead to increased morbidity and mortality. Osteoclasts are responsible for bone resorption in bone-related disorders. Genipin is a well-known geniposide aglycon derived from Gardenia jasminoides, which has long been used in oriental medicine for controlling diverse conditions such as inflammation and infection. Objectives: We aimed to evaluate the effects of genipin on RANKL-induced osteoclast differentiation and its mechanism of action. Results: Genipin dose-dependently inhibited early stage RANKL-induced osteoclast differentiation in bone marrow macrophages (BMMs) during culture. Genipin inhibited RANKL-induced IκB degradation and suppressed the mRNA expression of osteoclastic markers such as NFATc1, TRAP, and OSCAR in RANKL-treated BMMs, but did not affect c-Fos mRNA expression. Interestingly, genipin markedly inhibited c-Fos protein expression in BMMs, which was reversed in the presence of the proteosome inhibitor MG-132. Furthermore, genipin inhibited RANKL-mediated osteoclast differentiation, which was also rescued by overexpression of c-Fos and NFATc1 in BMMs. Conclusions: Taken together, our findings indicate that genipin down-regulated RANKL-induced osteoclast differentiation through inhibition of c-Fos protein proteolysis as well as inhibition of IκB degradation. Our findings indicate that genipin could be a useful drug candidate that lacks toxic side effects for the treatment of osteoporosis. Disclosure of Interest: None declared DOI: 10.1136/annrheumdis-2014-eular.2308