Korean J Anat.
2008 Dec;41(4):265-270.
Effect of Jak2 Inhibitor AG490 on Osteoclast Differentiation
- Affiliations
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- 1Department of Anatomy, School of Medicine, Wonkwang University, Iksan, Jeonbuk 570-749, Korea. Jmoh@wonkwang.ac.kr
- 2Department of Rheumatology, School of Medicine, Wonkwang University, Iksan, Jeonbuk 570-749, Korea.
- 3Department of Obstetrics and Gynecology, School of Medicine, Wonkwang University, Iksan, Jeonbuk 570-749, Korea.
- 4Department of Pathology, School of Medicine, Wonkwang University, Iksan, Jeonbuk 570-749, Korea.
- 5Department of Orthopaedic Sugery, School of Medicine, Wonkwang University, Iksan, Jeonbuk 570-749, Korea.
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-kappaB ligand (RANKL)-mediated osteoclast differentiation in a dose-dependent manner. RANKL stimulated the phosphorylation of p38, ERK, and JNK and promoted I-kappaB 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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