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- Title
The 4-1BB ligand and 4-1BB expressed on osteoclast precursors enhance RANKL-induced osteoclastogenesis via bi-directional signaling.
- Authors
Yang, Jihyun; Park, Ok Jin; Lee, Yeon Ju; Jung, Hong-Moon; Woo, Kyung Mi; Choi, Youngnim
- Abstract
The 4-1BB is a costimulatory molecule similar to the receptor activator of NF-κB 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 4-1BBmice 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. Supporting Information for this article is available at www.wiley-vch.de/contents/jc_2040/2008/37650_s.pdf
- Publication
European Journal of Immunology, 2008, Vol 38, Issue 6, p1598
- ISSN
0014-2980
- Publication type
Article
- DOI
10.1002/eji.200737650