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

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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
Author(s)
C H Lee; S C Kwak; J Y Kim; Hyun-Mee Oh; Mun Chual Rho; K H Yoon; W H Yoo; M S Lee; J Oh
Bibliographic Citation
Journal of Pharmacological Sciences, vol. 124, no. 3, pp. 344-353
Publication Year
2014
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.
Keyword
c-FosDifferentiationGenipinNFATc1Osteoclast
ISSN
1347-8613
Publisher
Japanese Pharmacological Soc
DOI
http://dx.doi.org/10.1254/jphs.13174FP
Type
Article
Appears in Collections:
Jeonbuk Branch Institute > Immunoregulatory materials Research Center > 1. Journal Articles
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