Journal of the Korean Academy of Pediatric Dentistry 2008;35(4):597-606.
Published online November 30, 2008.
STUDY ON THE REGULATION OF OSTEOCLAST AND T CELL ACTIVATION VIA CELL MEMBRANE PROTEINS OF TNF FAMILY, CD137 LIGAND AND RANK LIGAND
Sung-Joon Hong1, Jae-Hong Park1, Hyeon-Woo Lee2, Keung-Ho Lee1
1Department of Pediatric Dentistry, School of Dentistry, Kyung Hee University
2Department of Phamacology and Institute of Oral Biology, School of Dentistry, Kyung Hee University 
TNF계 CD137L 및 RANKL의 파골세포와 T 세포에 대한 활성조절
홍성준1, 박재홍1, 이현우2, 이긍호1
1경희대학교 치과대학 소아치과학교실
2경희대학교 치과대학 치과약리학교실, 구강생물학 연구소
Correspondence:  Jae-Hong Park,  Tel: 02-958-9373, Email: pedopjh@khu.ac.kr
Received: 18 April 2008   • Accepted: 8 July 2008
Abstract
Resorption of alveolar bone in periodontitis is due to excessive differentiation and activation of osteoclasts. Bacterial antigens causing periodontitis activates CD4 T cells, which leads to expressing RANK ligand (RANKL) on CD4 T cells. RANKL binds RANK on preosteoclasts or osteoclasts, and enhances the differentiation preosteoclasts into osteoclasts and the activation of mature osteoclasts. CD137, one of TNF receptor (TNFR) family, expressed on activated T cells binds with CD137 ligand (CD137L) on antigen presenting cells. Cross-linking of CD137 by CD137L acts as T cell co-stimulatory signals and, therefore, enhances the activation of T cell. In this study, I elucidated the biological responses of CD137L on (pre)osteoclasts and RANKL on T cells in the context of in vivo interaction between T cells and osteoclasts. RAW264.7, murine monocytic cells, constitutively express CD137L. Ligation of CD137L with anti-CD137L mAb inhibited RANKL-induced osteoclast formation in a dosedependent manner. Bone marrow cells are expressed CD137L by the treatment with M-CSF. Cross-linking of CD137L abolished M-CSF/ RANKL-evoked the formation of multi-nucleated osteoclasts. Both mouse CD4 and CD8 T cells are expressed RANKL following their activation. Ligation of RANKL with OPG, the decoy receptor for RANKL, inhibited both CD4 and CD8 T cell proliferation. These effects were attributed to RANKL-induced apoptosis. These data indicate that CD137L and RANKL on osteoclasts and T cells, respectively provide them with inhibitory signal.
Key Words: RANKL, CD137L, Osteoclast, T lymphocyte
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