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Title 

Genipin inhibits RANKL-induced osteoclast differentiation through proteasome-mediated degradation of c-Fos protein and suppression of NF-κB activation

Authors 

C H LeeS C KwakJ Y KimHyun-Mee OhMun Chual RhoK H YoonW H YooM S LeeJ Oh

Publisher 

Japanese Pharmacological Society

Issue Date 

2014

Citation 

Journal of Pharmacological Sciences, vol. 124, no. 3, pp. 344-353

Keywords 

c-FosDifferentiationGenipinNFATc1Osteoclast

Abstract 

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. We aimed to evaluate the effects of genipin on RANKL-induced osteoclast differentiation and its mechanism of action. Genipin dose-dependently inhibited early stage RANKL-induced osteoclast differentiation in bone marrow macrophages (BMMs) during culture. Genipin inhibited RANKL-induced IkB 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. 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.

ISSN 

1347-8613

Link 

http://dx.doi.org/10.1254/jphs.13174FP

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2017-04-19


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