R848, a toll-like receptor 7 agonist, inhibits osteoclast differentiation but not survival or bone-resorbing function of mature osteoclasts
  • Miyamoto, Arei
  • Takami, Masamichi
  • Matsumoto, Akifumi
  • Mochizuki, Ayako
  • Yamada, Takako
  • ... Yim, Mijung
  • 외 8명
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초록

R848, also known as resiquimod, acts as a ligand for toll-like receptor 7 (TLR7) and activates immune cells. In this study, we examined the effects of R848 on differentiation, survival, and bone-resorbing function of osteoclasts. R848 inhibited osteoclast differentiation of mouse bone marrow-derived macrophages (BMMs) and human peripheral blood-derived monocytes induced by receptor activator of NF-kappa B ligand in a dose-dependent manner. In addition, it inhibited mouse osteoclast differentiation induced in cocultures of bone marrow cells and osteoblasts in the presence of dihydroxyvitamin D-3 [1,25(OH)(2)D-3]. However, R848 did not affect the survival or bone-resorbing activity of mouse mature osteoclasts. R848 also upregulated the mRNA expression levels of interleukin (IL)-6, IL-12, interferon (IFN)-gamma, and inducible nitric oxide synthase in mouse BMMs expressing TLR7. IFN-beta was consistently expressed in the BMMs and addition of neutralizing antibodies against IFN-beta to the cultures partially recovered osteoclast differentiation inhibited by R848. These results suggest that R848 targets osteoclast precursors and inhibits their differentiation into osteoclasts via TLR7.

키워드

R848ResiquimodOsteoclastsToll-like receptorCellular differentiationBoneNF-KAPPA-BPATTERN-RECOGNITION RECEPTORSOSTEOBLASTIC CELLSINTERFERON-BETAINNATE IMMUNITYRANKLSTIMULATIONEXPRESSIONRESORPTIONLIGAND
제목
R848, a toll-like receptor 7 agonist, inhibits osteoclast differentiation but not survival or bone-resorbing function of mature osteoclasts
저자
Miyamoto, AreiTakami, MasamichiMatsumoto, AkifumiMochizuki, AyakoYamada, TakakoTachi, KeitaShibuya, IsaoNakamachi, TomoyaShioda, SeijiBaba, KazuyoshiInoue, TomioMiyamoto, YoichiYim, MijungKamijo, Ryutaro
DOI
10.1007/s10616-012-9442-5
발행일
2012-05
유형
Article; Proceedings Paper
저널명
Cytotechnology
64
3
페이지
331 ~ 339