Effect of Jak2 Inhibitor AG490 on Osteoclast Differentiation.
- Author:
Chang Hoon LEE
1
;
Min Kyu CHOI
;
Jeong Joong KIM
;
Myeung Su LEE
;
Hae Joong CHO
;
Hun Soo KIM
;
Jeong Woo KIM
;
Jaemin OH
Author Information
1. Department of Anatomy, School of Medicine, Wonkwang University, Iksan, Jeonbuk 570-749, Korea. Jmoh@wonkwang.ac.kr
- Publication Type:Original Article
- Keywords:
Bone;
Osteoclast;
AG490;
RANKL
- MeSH:
Arthritis, Rheumatoid;
Bone Diseases;
Bone Resorption;
Macrophages;
Osteoclasts;
Osteoporosis;
Periodontal Diseases;
Phosphorylation;
Receptor Activator of Nuclear Factor-kappa B;
RNA, Messenger;
Tyrphostins
- From:Korean Journal of Anatomy
2008;41(4):265-270
- CountryRepublic of Korea
- Language:Korean
-
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.
