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The 4-1BB ligand and 4-1BB expressed on osteoclast precursors enhance RANKL-induced osteoclastogenesis via bi-directional signaling

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dc.contributor.authorYang, Jihyun-
dc.contributor.authorPark, Ok Jin-
dc.contributor.authorLee, Yeon Ju-
dc.contributor.authorJung, Hong-Moon-
dc.contributor.authorChoi, Youngnim-
dc.contributor.authorWoo, Kyung Mi-
dc.date.accessioned2013-01-14T05:52:39Z-
dc.date.available2013-01-14T05:52:39Z-
dc.date.issued2008-06-
dc.identifier.citationEUROPEAN JOURNAL OF IMMUNOLOGY, Vol.38, No.6, pp.1598-1609ko_KR
dc.identifier.issn0014-2980-
dc.identifier.urihttp://hdl.handle.net/10371/80370-
dc.description.abstractThe 4-1BB is a costimulatory molecule similar to the receptor activator of NF-kappa B ligand (RANKL), both of which are key factors for the differentiation of osteoclasts and are expressed mainly by activated T cells. The 4-1BB shares common signaling pathways with RANK, suggesting a potential role in osteoclastogenesis. In this study, the role of 4-1BB and 4-1BB ligand (4-1BBL) in osteoclastogenesis was investigated using 4-1BB(-/-) and 4-1BB(+/+) mice. osteoclast precursors normally express 4-1BB and 4-1BBL after exposure to RANKL, which was confirmed by semi-quantitative RT-PCR and flow cytometry. The 4-1BB(-/-) mice had a slightly increased bone mass accompanied by a reduced osteoclastogenic ability of 4-1BB(-/-) bone marrow-derived macrophages (BMM) ex vivo. In addition, 4-1BB(-/-) BMM demonstrated hypophosphorylation of JNK and p38 and decreased induction of c-Fos in response to RANKL stimulation. Retroviral transduction of wild-type as well as partial-length 4-1BB, which lacks TNF receptor-associated factor 2-binding sites for signaling, restored the osteoclastogenic ability of 4-1BB(-/-) BMM. Furthermore, both recombinant 4-1BB and 4-1BBL enhanced RANKL-induced osteoclastogenesis by 4-1BB(+/+) BMM and the induction of c-Fos and NFATc1.Together, these results indicate that 4-1BBL and 4-1BB expressed on osteoclast precursors enhance RANKL-induced osteoclastogenesis via bi-directional signaling, findings that may delineate the complex nature of the 4-1BBL and 4-1BB interaction.ko_KR
dc.description.sponsorshipThis study was supported by BK21 CLS to School of
Dentistry, Seoul National University and grants E00255 and E00292 to Dr. Youngnim Choi from the Korea Research Foundation.
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dc.language.isoenko_KR
dc.publisherWILEY-V C H VERLAG GMBHko_KR
dc.subject4-1BB/CD137ko_KR
dc.subjectosteoclastogenesisko_KR
dc.subject4-1BBLko_KR
dc.subjectbi-directional signalingko_KR
dc.titleThe 4-1BB ligand and 4-1BB expressed on osteoclast precursors enhance RANKL-induced osteoclastogenesis via bi-directional signalingko_KR
dc.typeArticleko_KR
dc.contributor.AlternativeAuthor양지현-
dc.contributor.AlternativeAuthor박옥진-
dc.contributor.AlternativeAuthor이연주-
dc.contributor.AlternativeAuthor정홍문-
dc.contributor.AlternativeAuthor최영님-
dc.contributor.AlternativeAuthor우경미-
dc.identifier.doi10.1002/eji.200737650-
dc.citation.journaltitleEUROPEAN JOURNAL OF IMMUNOLOGY-
dc.description.tc5-
Appears in Collections:
College of Dentistry/School of Dentistry (치과대학/치의학대학원)Dept. of Dentistry (치의학과)Journal Papers (저널논문_치의학과)
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