S-Space College of Dentistry/School of Dentistry (치과대학/치의학대학원) Dept. of Dentistry (치의학과) Journal Papers (저널논문_치의학과)
Interaction of Fas ligand (FasL) and Fas expressed on osteoclast precursors increases osteoclast differentiationogenesis.
- Park, hyewon; Jung, Youn-Kwan; Park, Ok-Jin; Lee, Yeon-Ju; Choi, Je-Yong; Choi, Young-Nim
- Issue Date
- American Association of Immunologists
- Journal of Immunology 175: 7193-7201
- We incidentally found that osteoclast precursors and mature osteoclasts express Fas ligand (FasL) as well as Fas, which was
confirmed by flow cytometry, immunofluorescent staining, and RT-PCR. The aim of this study was to determine the role of FasL
in differentiation and cell death of osteoclasts. To study the role of FasL in osteoclastogenesis, neutralizing anti-FasL mAb or rFasL
was added during receptor activator of NF- B ligand (RANKL)-induced osteoclastogenesis using bone marrow-derived macrophages.
Neutralization of endogenous FasL by anti-FasL mAb decreased osteoclastogenesis, whereas rFasL enhanced osteoclast
differentiation in a dose-dependent manner. In addition, rFasL up-regulated the secretion of osteoclastogenic cytokines, such as
IL-1 and TNF- , and the activation of NF- B. Functional blocking of IL-1 and TNF- using IL-1 receptor antagonist and
soluble TNFR confirmed that those cytokines mediated the effect of FasL on osteoclastogenesis. The osteoclast precursors were
relatively resistant to rFasL-induced apoptosis especially before RANKL treatment, resulting in minimal cell loss by rFasL
treatment during osteoclastogenesis. Although rFasL increased the cell death of mature osteoclasts, growth factor withdrawal
induced much more cell death. However, anti-FasL mAb did not affect the survival of mature osteoclasts, suggesting that the
endogenous FasL does not have a role in the apoptosis of osteoclasts. Finally, in contrast to the effect on apoptosis, rFasL-assisted
osteoclastogenesis was not mediated by caspases. In conclusion, FasL has a novel function in bone homeostasis by enhancing the
differentiation of osteoclasts, which was not considered previously.
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