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

Cited 10 time in Web of Science Cited 11 time in Scopus
Authors
Yang, Jihyun; Park, Ok Jin; Lee, Yeon Ju; Jung, Hong-Moon; Choi, Youngnim; Woo, Kyung Mi
Issue Date
2008-06
Publisher
WILEY-V C H VERLAG GMBH
Citation
EUROPEAN JOURNAL OF IMMUNOLOGY, Vol.38, No.6, pp.1598-1609
Keywords
4-1BB/CD137osteoclastogenesis4-1BBLbi-directional signaling
Abstract
The 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.
ISSN
0014-2980
Language
English
URI
http://hdl.handle.net/10371/80370
DOI
https://doi.org/10.1002/eji.200737650
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College of Dentistry/School of Dentistry (치과대학/치의학대학원)Dept. of Dentistry (치의학과)Journal Papers (저널논문_치의학과)
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