Browse

Antioxidant -lipoic acid inhibits osteoclast differentiation by reducing nuclear factor-kappa B DNA binding and prevents in vivo bone resorption induced by RANKL and TNF-alpha.

Cited 104 time in Web of Science Cited 108 time in Scopus
Authors
Kim, Hyon Jong; Chang, Eun-Ju; Kim, Hyun-Man; Lee, Seung Bok; Kim, Hyun-Duck; Kim, Ghi Su; Kim, Hong-Hee
Issue Date
2006-05
Publisher
Elsevier
Citation
Free Radic Biol Med. 40(9):1483-1493
Keywords
AntioxidantLipoic acidOsteoclast differentiationCytokinesα-Nuclear factor kappa BBone resorptionFree radical
Abstract
The relationship between oxidative stress and bone mineral density or osteoporosis has recently been reported. As bone loss occurring in osteoporosis and inflammatory diseases is primarily due to increases in osteoclast number, reactive oxygen species (ROS) may be relevant to osteoclast differentiation, which requires receptor activator of nuclear factor-κB ligand (RANKL). Tumor necrosis factor-α (TNF-α) frequently present in inflammatory conditions has a profound synergy with RANKL in osteoclastogenesis. In this study, we investigated the effects of α-lipoic acid (α-LA), a strong antioxidant clinically used for some time, on osteoclast differentiation and bone resorption. At concentrations showing no growth inhibition, α-LA potently suppressed osteoclastogenesis from bone marrow-derived precursor cells driven either by a high-dose RANKL alone or by a low-dose RANKL plus TNF-α (RANKL/TNF-α). α-LA abolished ROS elevation by RANKL or RANKL/TNF-α and inhibited NF-κB activation in osteoclast precursor cells. Specifically, α-LA reduced DNA binding of NF-κB but did not inhibit IKK activation. Furthermore, α-LA greatly suppressed in vivo bone loss induced by RANKL or TNF-α in a calvarial remodeling model. Therefore, our data provide evidence that ROS plays an important role in osteoclast differentiation through NF-κB regulation and the antioxidant α-lipoic acid has a therapeutic potential for bone erosive diseases.
ISSN
0891-5849
Language
English
URI
https://hdl.handle.net/10371/69608
DOI
https://doi.org/10.1016/j.freeradbiomed.2005.10.066
Files in This Item:
There are no files associated with this item.
Appears in Collections:
College of Dentistry/School of Dentistry (치과대학/치의학대학원)Dept. of Dentistry (치의학과)Journal Papers (저널논문_치의학과)
  • mendeley

Items in S-Space are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse