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AB0094 Genipin Inhibits Rankl-Induced Osteoclast Differentiation Through
  1. C.-H. Lee1,
  2. J.-Y. Kim2,
  3. J.-M. Oh2,
  4. W.-H. Yoo3,
  5. S.-H. Beak4,
  6. J.-J. Choi5,
  7. W.-S. Lee3,
  8. M.-S. Lee1
  1. 1Internal medicine, Wonkwang University Hospital
  2. 2Anatomy, Wonkwang University, Iksan
  3. 3Internal medicine, Chonbuk National University Medical School and Research Institute of Clinical Medicine, Jeonju
  4. 4Internal medicine, Ilsin Christian Hospital, Busan
  5. 5Internal medicine, CHA Hospital, Pochon CHA University, Seungnam, Korea, Republic Of

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

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