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KMID : 0363720080410040265
Korean Journal of Anatomy
2008 Volume.41 No. 4 p.265 ~ p.270
Effect of Jak2 Inhibitor AG490 on Osteoclast Differentiation
Lee Chang-Hoon

Choi Min-Kyu
Kim Jeong-Joong
Lee Myeong-Soo
Cho Hae-Joong
Kim Hun-Soo
Kim Jeong-Woo
Oh Jae-Min
Abstract
Osteoclasts are cells of hemopoietic origin that play an critical role in bone resorption and responsible for bone diseases, including osteoporosis, periodontal disease, and rheumatoid arthritis. In this study, we examined the effect of AG490, a Jak2-specific inhibitor on osteoclast differentiation. AG490 significantly inhibited receptor activator of NF-¥êB ligand (RANKL)-mediated osteoclast differentiation in a dose-dependent manner. RANKL stimulated the phosphorylation of p38, ERK, and JNK and promoted I-¥êB degradation. However, AG490 suppressed the phosphorylation of p38 induced by RANKL treatment. AG490 suppressed the mRNA expression of TRAP, c-Fos, NFATc1, and OSCAR in bone marrow-derived macrophages (BMMs) treated with RANKL. Also, AG490 significantly inhibited the protein expression of c-Fos and NFATc1 in response to RANKL. These results suggest that AG490 inhibited osteoclast differentiation by suppressing the expression of c-Fos and NFATc1.
KEYWORD
Bone, Osteoclast, AG490, RANKL
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