title: Mizoribine may suppress bone erosion in patients with rheumatoid arthritis by inhibiting osteoclastogenesis.
abstract: Mizoribine is a disease-modifying anti-rheumatic drug (DMARD) that is used in the treatment of rheumatoid arthritis. However, clinical use of the drug is restricted to a few Asian countries due to a lack of comprehensive evidence on its effectiveness. The inhibitory effect of the drug on human osteoclastogenesis was investigated in the hopes of providing some clear evidence. Mizoribine was found to inhibit in vitro osteoclastogenesis in a dose-dependent manner. In addition, the size of the pit area was closely related to the number of osteoclasts in a bone resorption assay. However, mizoribine did not affect the phosphorylation of MAP kinase (p38, JNK, ERK), the degradation of IkappaBalpha, or receptor activator of NF-kappaB ligand (RANKL) expression in fibroblast-like synoviocytes stimulated with IL-1beta. These results suggested that mizoribine may partially suppress osteoclastogenesis, leading to progressive bone erosion by inhibiting the growth or the signaling pathway of precursor cells to form osteoclasts rather than fibroblast-like synoviocytes.
authors.affiliation: Dept of Internal Medicine, College of Medicine, Kyung Hee University, Dongdaemun-gu, Seoul, Republic of Korea.
authors.forename: Yeon-Ah
authors.initials: YA
authors.lastname: Lee
authors.forename: Hyung-In
authors.initials: HI
authors.lastname: Yang
authors.forename: Eun Kyung
authors.initials: EK
authors.lastname: Park
authors.forename: Jun Soo
authors.initials: JS
authors.lastname: Bang
authors.forename: Hyun Mi
authors.initials: HM
authors.lastname: Choi
authors.forename: Da Hee
authors.initials: DH
authors.lastname: Oh
authors.forename: Sang-Hoon
authors.initials: SH
authors.lastname: Lee
authors.forename: Seung-Jae
authors.initials: SJ
authors.lastname: Hong
authors.forename: Yoon-Je
authors.initials: YJ
authors.lastname: Jo
authors.forename: Myung Chul
authors.initials: MC
authors.lastname: Yoo
authors.forename: Kyoung Soo
authors.initials: KS
authors.lastname: Kim
mesh_terms: D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000503:physiopathology; D001862:Bone Resorption / Q000517:prevention & control; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D066298:In Vitro Techniques; D010010:Osteoclasts / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D012263:Ribonucleosides / Q000008:administration & dosage / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D007166:Immunosuppressive Agents; D012263:Ribonucleosides; C010052:mizoribine