R848, a toll-like receptor 7 agonist, inhibits osteoclast differentiation but not survival or bone-resorbing function of mature osteoclasts.

Cytotechnology
Arei MiyamotoRyutaro Kamijo

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-κB 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)-γ, and inducible nitric oxide synthase in mouse BMMs expressing TLR7. IFN-β was consistently expressed in the BMMs and addition of neutralizing antibodies against IFN-β 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.

References

Nov 1, 1988·Endocrinology·N TakahashiT Suda
Mar 19, 1999·Biochemical and Biophysical Research Communications·N TakahashiT Suda
Feb 15, 2000·The Journal of Biological Chemistry·Y AzumaA Kudo
Apr 6, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·N J HorwoodM T Gillespie
Apr 19, 2002·Nature·Hiroshi TakayanagiTadatsugu Taniguchi
Jul 23, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Masamichi TakamiYongwon Choi
Jul 22, 2004·Experimental Cell Research·Seung Ku LeeHong-Hee Kim
Jun 16, 2005·American Journal of Physiology. Endocrinology and Metabolism·Charles A O'BrienStavros C Manolagas
Feb 25, 2006·Cell·Shizuo AkiraOsamu Takeuchi
Sep 20, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ayako MochizukiRyutaro Kamijo
Dec 28, 2006·Journal of Biochemistry·Taro Kawai, Shizuo Akira
Jan 16, 2010·Science·Akiko Iwasaki, Ruslan Medzhitov
Mar 10, 2011·Nature Reviews. Rheumatology·James R Edwards, Gregory R Mundy

❮ Previous
Next ❯

Citations

Sep 25, 2015·Biochemical and Biophysical Research Communications·Hiroaki SuzukiRyutaro Kamijo
Jul 12, 2018·Journal of Cellular and Molecular Medicine·Anita FischerGünter Steiner
May 18, 2020·Cellular & Molecular Immunology·Sadiq UmarShiva Shahrara
May 16, 2019·Journal of Biochemistry·Kyoung-Woon KimSang-Heon Lee
Dec 19, 2016·Autoimmunity Reviews·Hatem A ElshabrawyShiva Shahrara
May 4, 2021·Arthroscopy : the Journal of Arthroscopic & Related Surgery : Official Publication of the Arthroscopy Association of North America and the International Arthroscopy Association·Adam W AnzKhay-Yong Saw
Nov 7, 2020·Frontiers in Immunology·Anett B HegewaldMeike J Saul

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.