title: [Disease modifying antirheumatic drugs with inhibitory effect on osteoclastogenesis].
abstract: Suppression of bone destruction is a requirement for effective therapeutic strategies for autoimmune arthritis. Although numerous antirheumatic drugs are in clinical use, little is known about whether they ameliorate bone destruction by acting on activated T cells or other cell types, such as bone-resorbing osteoclasts. Leflunomide has a direct inhibitory effect on RANKL-mediated osteoclast differentiation by inhibiting the induction of NFATc1, the master switch regulator for osteoclast differentiation. We show that the direct inhibitory action of leflunomide on osteoclast differentiation constitutes an important aspect to ameliorate bone destruction, and that RANKL dependent NFATc1 induction pathway is an auspicious target for pharmacological intervention into arthritic bone destruction.
authors.affiliation: Department of Orthopaedic Surgery, Juntendo University School of Medicine.
authors.forename: Makoto
authors.initials: M
authors.lastname: Urushibara
mesh_terms: D018501:Antirheumatic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D002454:Cell Differentiation; D006801:Humans; D007555:Isoxazoles / Q000494:pharmacology / Q000627:therapeutic use*; D000077339:Leflunomide; D010010:Osteoclasts / Q000187:drug effects / Q000502:physiology
chemical_list: D018501:Antirheumatic Agents; D007555:Isoxazoles; D000077339:Leflunomide