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PAMM: a redox regulatory protein that modulates osteoclast differentiation
Odgren Lab
  • Yan Xu, Harvard Medical School
  • Leslie R. Morse, Harvard University School of Medicine
  • Raquel Assed Bezerra da Silva, University of Sao Paulo
  • Paul R. Odgren, University of Massachusetts Medical School
  • Hajime Sasaki, The Forsyth Institute
  • Philip Stashenko, The Forsyth Institute
  • Ricardo A. Battaglino, The Forsyth Institute
UMMS Affiliation
Department of Cell Biology
Date
7-1-2010
Document Type
Article
Medical Subject Headings
Reactive Oxygen Species; Oxidation-Reduction; Osteoclasts; Cell Differentiation
Disciplines
Abstract

The central role of reactive oxygen species (ROS) in osteoclast differentiation and in bone homeostasis prompted us to characterize the redox regulatory system of osteoclasts. In this report, we describe the expression and functional characterization of PAMM, a CXXC motif-containing peroxiredoxin 2-like protein expressed in bone marrow monocytes on stimulation with M-CSF and RANKL. Expression of wild-type (but not C to G mutants of the CXXC domain) PAMM in HEK293 cells results in an increased GSH/GSSG ratio, indicating a shift toward a more reduced environment. Expression of PAMM in RAW264.7 monocytes protected cells from hydrogen peroxide-induced oxidative stress, indicating that PAMM regulates cellular redox status. RANKL stimulation of RAW 264.7 cells caused a decrease in the GSH/GSSG ratio (reflecting a complementary increase in ROS). In addition, RANKL-induced osteoclast formation requires phosphorylation and translocation of NF-kappaB and c-Jun. In stably transfected RAW 264.7 cells, PAMM overexpression prevented the reduction of GSH/GSSG induced by RANKL. Concurrently, PAMM expression completely abolished RANKL-induced p100 NF-kappaB and c-Jun activation, as well as osteoclast formation. We conclude that PAMM is a redox regulatory protein that modulates osteoclast differentiation in vitro. PAMM expression may affect bone resorption in vivo and help to maintain bone mass.

Rights and Permissions
Citation: Yan Xu, Leslie R. Morse, Raquel Assed Bezerra da Silva, Paul R. Odgren, Hajime Sasaki, Philip Stashenko, Ricardo A. Battaglino. Antioxidants & Redox Signaling. July 1, 2010, 13(1): 27-37. doi:10.1089/ars.2009.2886. Link to article on publisher's site
Related Resources
Link to Article in PubMed
PubMed ID
19951071
Citation Information
Yan Xu, Leslie R. Morse, Raquel Assed Bezerra da Silva, Paul R. Odgren, et al.. "PAMM: a redox regulatory protein that modulates osteoclast differentiation" Vol. 13 Iss. 1 (2010) ISSN: 1523-0864 (Linking)
Available at: http://works.bepress.com/paul_odgren/10/