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Infection and Immunity, May 2009, p. 2000-2009, Vol. 77, No. 5
0019-9567/09/$08.00+0     doi:10.1128/IAI.01070-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Involvement of SOCS3 in Regulation of CD11c+ Dendritic Cell-Derived Osteoclastogenesis and Severe Alveolar Bone Loss {triangledown}

Xiaoxia Zhang,1 Mawadda Alnaeeli,1,3 Bhagirath Singh,2 and Yen-Tung A. Teng1,3*

Laboratory of Molecular Microbial Immunity, Division of Periodontology, The Eastman Department of Dentistry, and Department of Microbiology and Immunology, School of Medicine and Dentistry, University of Rochester, Rochester, New York 14620,1 Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, Ontario N6A 5C1, Canada,2 Center for Osteoimmunology and Biotechnology Research, College of Dental Medicine, Kaohsiung Medical University and University Hospital, Kaohsiung, Taiwan3

Received 27 August 2008/ Returned for modification 16 October 2008/ Accepted 20 February 2009

To investigate the role of suppressor of cytokine signaling (SOCS) molecules in periodontal immunity and RANKL-mediated dendritic cell (DC)-associated osteoclastogenesis, we analyzed SOCS expression profiles in CD4+ T cells and the effect of SOCS3 expression in CD11c+ DCs during periodontal inflammation-induced osteoclastogenesis and bone loss in nonobese diabetic (NOD) versus humanized NOD/SCID mice. Our results of ex vivo and in vitro analyses showed that (i) there is significantly higher SOCS3 expression associated with RANKL+ T-cell-mediated bone loss in correlation with increased CD11c+ DC-mediated osteoclastogenesis; (ii) the transfection of CD11c+ DC using an adenoviral vector carrying a dominant negative SOCS3 gene significantly abrogates TRAP and bone-resorptive activity; and (iii) inflammation-induced TRAP expression, bone resorption, and SOCS3 activity are not associated with any detectable change in the expression levels of TRAF6 and mitogen-activated protein kinase signaling adaptors (i.e., Erk, Jnk, p38, and Akt) in RANKL+ T cells. We conclude that SOCS3 plays a critical role in modulating cytokine signaling involved in RANKL-mediated DC-derived osteoclastogenesis during immune interactions with T cells and diabetes-associated severe inflammation-induced alveolar bone loss. Therefore, the development of SOCS3 inhibitors may have therapeutic potential as the target to halt inflammation-induced bone loss under pathological conditions in vivo.

* Corresponding author. Mailing address: The Eastman Dental Center, University of Rochester Medical Center, Box 683, 625 Elmwood Ave., Rochester, NY 14620. Phone: (585) 275-7309. Fax: (585) 473-5254. E-mail: andy_teng{at}urmc.rochester.edu

{triangledown} Published ahead of print on 2 March 2009.

Editor: F. C. Fang

Infection and Immunity, May 2009, p. 2000-2009, Vol. 77, No. 5
0019-9567/09/$08.00+0     doi:10.1128/IAI.01070-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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