Korean J Bone Metab > Volume 17(1); 2010 > Article
Korean Journal of Bone Metabolism 2010;17(1):13-18.
Pyridone 6, a Pan-Janus-activated Kinase Inhibitor, Suppresses Osteoclast Formation and Bone Resorption in Inflammatory Bone Loss
염증성 골 소실 질환에서 범-Jak 억제제인 Pyridone 6의 골 흡수 억제 효과
김헌수,곽한복1,오재민1,연정태1,최식원1,이명수2
원광의대 병리과, 해부학교실1, 류마티스 내과2
Abstract
Objective
The role of JAK on osteoclast differentiation and anti-bone resorptive activity has been recently reported but the study in vivo is not well defined. In this study, we investigated the effects of a pan-JAK inhibitor, pyridone 6, on osteoclast differentiation and bone-resorption and inflammatory bone loss model in vivo.
Methods
Mature osteoclasts were obtained using a coculture system from bone marrow cells and calvarial osteoblasts with or without pyridone 6 in various concentrations. ICR mice were orally administered pyridone 6 or PBS 1 day before the injection of LPS and every other day for 8 days. The femurs were obtained and micro-CT images, and histologic sections were obtained with TRAP staining.
Results
Pyridone 6 inhibited osteoclast differentiation in co-cultures stimulated by LPS. Micro-CT and histologic analysis of the femurs showed that the bone loss caused by LPS treatment was significantly attenuated in mouse administered with pyridone 6.
Conclusion
These results demonstrate inhibition of JAK may be useful for the treatment of bone-resorptive diseases, such as osteoporosis. [Korean Journal of Bone Metabolism, 17(1): 13-18, 2010]
Key Words: Janus kinases, Pyridone 6, Osteoclasts, RANK ligand
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