Skip Navigation

Journal of Biochemistry 2006 139(3):583-590; doi:10.1093/jb/mvj066
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Request Permissions
Google Scholar
Right arrow Articles by Yoshida, H.
Right arrow Articles by Kato, Y.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Yoshida, H.
Right arrow Articles by Kato, Y.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 2006 The Japanese Biochemical Society.

Regular Paper

Pepstatin A, an Aspartic Proteinase Inhibitor, Suppresses RANKL-Induced Osteoclast Differentiation

Hajime Yoshida1,2, Kuniaki Okamoto2,*, Tsutomu Iwamoto1, Eiko Sakai2, Kazuhiro Kanaoka3, Jin-Ping Hu2, Mitsue Shibata2, Hitoshi Hotokezaka3, Kazuhisa Nishishita2, Akio Mizuno1 and Yuzo Kato2

Divisions of 1 Oral and Maxillofacial Surgery, 2 Oral Molecular Pharmacology, and 3 Orthodontics and Biomedical Engineering, Department of Development and Reconstructive Medicine, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8588

* To whom correspondence should be addressed. Tel: +81-95-849-7653, Fax: +81-95-849-7655, E-mail: k-oka{at}net.nagasaki-u.ac.jp

Pepstatin A is well known to be an inhibitor of aspartic proteinases such as pepsin, cathepsins D and E. Except for its role as a proteinase inhibitor, however, the pharmacological action of pepstatin A upon cells remain unclear. In this study, we found that pepstatin A suppressed receptor activator of NF-{kappa}B ligand (RANKL)–induced osteoclast differentiation. Pepstatin A suppressed the formation of multinuclear osteoclasts dose-dependently. This inhibition of the formation only affected osteoclast cells, i.e., not osteoblast-like cells. Furthermore, pepstatin A also suppressed differentiation from pre-osteoclast cells to mononuclear osteoclast cells dose-dependently. This inhibition seems to be independent of the activities of proteinases such as cathepsin D, because the formation of osteoclasts was not suppressed with the concentration that inhibited the activity of cathepsin D. Cell signaling analysis indicated that the phosphorylation of ERK was inhibited in pepstatin A-treated cells, while the phosphorylation of I{kappa}B and Akt showed almost no change. Furthermore, pepstatin A decreased the expression of nuclear factor of activated T cells c1 (NFATc1). These results suggest that pepstatin A suppresses the differentiation of osteoclasts through the blockade of ERK signaling and the inhibition of NFATc1 expression.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Acta Biochim Biophys SinHome page
K. Tveten, T. Ranheim, K. E. Berge, T. P. Leren, and M. A. Kulseth
The effect of bafilomycin A1 and protease inhibitors on the degradation and recycling of a Class 5-mutant LDLR
Acta Biochim Biophys Sin, March 1, 2009; 41(3): 246 - 255.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
Y. Zavros
The Adventures of Sonic Hedgehog in Development and Repair. IV. Sonic hedgehog processing, secretion, and function in the stomach
Am J Physiol Gastrointest Liver Physiol, May 1, 2008; 294(5): G1105 - G1108.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.