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Pepstatin A, an Aspartic Proteinase Inhibitor, Suppresses RANKL-Induced Osteoclast Differentiation.
- Source :
- Journal of Biochemistry; Mar2006, Vol. 139 Issue 3, p583-590, 8p
- Publication Year :
- 2006
-
Abstract
- 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-κB 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 IκB 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. [ABSTRACT FROM PUBLISHER]
- Subjects :
- ASPARTIC proteinases
PEPSIN
OSTEOCLASTS
CELLS
T cells
Subjects
Details
- Language :
- English
- ISSN :
- 0021924X
- Volume :
- 139
- Issue :
- 3
- Database :
- Complementary Index
- Journal :
- Journal of Biochemistry
- Publication Type :
- Academic Journal
- Accession number :
- 44566829
- Full Text :
- https://doi.org/10.1093/jb/mvj066