R848, a toll-like receptor 7 agonist, inhibits osteoclast differentiation but not survival or bone-resorbing function of mature osteoclasts
- Authors
- Miyamoto, Arei; Takami, Masamichi; Matsumoto, Akifumi; Mochizuki, Ayako; Yamada, Takako; Tachi, Keita; Shibuya, Isao; Nakamachi, Tomoya; Shioda, Seiji; Baba, Kazuyoshi; Inoue, Tomio; Miyamoto, Yoichi; Yim, Mijung; Kamijo, Ryutaro
- Issue Date
- May-2012
- Publisher
- SPRINGER
- Keywords
- R848; Resiquimod; Osteoclasts; Toll-like receptor; Cellular differentiation; Bone
- Citation
- CYTOTECHNOLOGY, v.64, no.3, pp 331 - 339
- Pages
- 9
- Journal Title
- CYTOTECHNOLOGY
- Volume
- 64
- Number
- 3
- Start Page
- 331
- End Page
- 339
- URI
- https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/11924
- DOI
- 10.1007/s10616-012-9442-5
- ISSN
- 0920-9069
1573-0778
- Abstract
- 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.
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