Mizoribine may suppress bone erosion in patients with rheumatoid arthritis by inhibiting osteoclastogenesis.
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.
Lee
Yeon-Ah
YA
Dept of Internal Medicine, College of Medicine, Kyung Hee University, Dongdaemun-gu, Seoul, Republic of Korea.
Yang
Hyung-In
HI
Park
Eun Kyung
EK
Bang
Jun Soo
JS
Choi
Hyun Mi
HM
Oh
Da Hee
DH
Lee
Sang-Hoon
SH
Hong
Seung-Jae
SJ
Jo
Yoon-Je
YJ
Yoo
Myung Chul
MC
Kim
Kyoung Soo
KS
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
D007166:Immunosuppressive Agents; D012263:Ribonucleosides; C010052:mizoribine