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KMID : 0438420100170010013
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Korean Journal of Bone Metabolism
2010 Volume.17 No. 1 p.13 ~ p.18
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Pyridone 6, a Pan-Janus-activated Kinase Inhibitor, Suppresses Osteoclast Formation and Bone Resorption in Inflammatory Bone Loss
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Kim Hun-Soo
Kwak Han-Bok
Oh Jae-Min
Yeun Jung-Tae
Choi Shik-Won
Lee Myeung-Su
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Abstract
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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.
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KEYWORD
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Janus kinases, Pyridone 6, Osteoclasts, RANK ligand
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