The active metabolite of leflunomide, A771726, inhibits both the generation of and the bone-resorbing activity of osteoclasts by acting directly on cells of the osteoclast lineage.

Journal of Bone and Mineral Metabolism
Yukinao KobayashiYoshiyuki Hakeda

Abstract

Leflunomide is a disease-modifying antirheumatic drug that inhibits paw swelling and joint destruction in type II collagen-induced arthritis in mice and it also delays disease progression in patients with rheumatoid arthritis (RA), through inhibiting proliferation and cytokine production of T cells, via the blocking of de-novo pyrimidine biosynthesis by its active metabolite, A771726. However, the direct action of leflunomide on cells of osteoclast lineage responsible for bone destruction in RA remains to be clarified. In this study, we examined the effect of A771726 on osteoclast formation and bone-resorbing activity in vitro, using cultures of bone marrow-derived osteoclast progenitors and purified functionally mature osteoclasts, and then we elucidated the molecular mechanism of action of the effect of A771726 on osteoclasts. A771726 inhibited osteoclast formation from macrophage colony-stimulating factor (M-CSF)-dependent osteoclast progenitors in the presence of receptor activator of nuclear factor kappa B (NF-kappaB) ligand (RANKL), without any other types of cells present, in a dose-related manner, similar to the inhibition in cultures of unfractionated bone marrow cells. In addition, A771726 suppressed bone resorption b...Continue Reading

Citations

Jun 19, 2013·Osteoporosis International : a Journal Established As Result of Cooperation Between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA·M VisW F Lems
May 18, 2005·Annals of the Rheumatic Diseases·J K Franz, G-R Burmester
May 19, 2005·Arthritis Research & Therapy·Bernhard M KirschMarcus D Säemann
Sep 21, 2013·Future Medicinal Chemistry·Qian-Qian HanPi-Shan Yang
Mar 25, 2015·Expert Opinion on Drug Metabolism & Toxicology·Anna Klukovits, Peter Krajcsi
Jun 14, 2005·Journal of Clinical Pharmacology·Tanya Doan, Elena Massarotti
Sep 30, 2008·Arthritis and Rheumatism·Georg SchettBernhard Manger
Jan 28, 2015·Expert Opinion on Pharmacotherapy·Jos N HoesWillem F Lems
May 12, 2016·Clinical Reviews in Allergy & Immunology·Sofia Carvalho Barreira, João Eurico Fonseca
Apr 20, 2006·Journal of Bone and Mineral Metabolism·Chie WadaToshihiko Nagata
Jan 1, 2006·Expert Review of Clinical Immunology·Gary Kunkel, Grant W Cannon
Jan 5, 2012·Nihon Rinshō Men'eki Gakkai kaishi = Japanese journal of clinical immunology·Yuki NankeShigeru Kotake
Jan 11, 2020·Journal of Cellular and Molecular Medicine·Md Abdullah Al MamunMd Abdul Alim Al-Bari
Apr 14, 2021·Journal of Pharmaceutical Sciences·Mariam ZewailNabila Boraie
May 1, 2021·Journal of Clinical Medicine·Meletios RozisDimitrios Stergios Evangelopoulos

❮ 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.