Pyridone 6, A Pan-Janus-Activated Kinase Inhibitor, Suppresses Osteoclast Formation and Bone Resorption through Down-Regulation of Receptor Activator of Nuclear Factor-.KAPPA.B (NF-.KAPPA.B) Ligand (RANKL)-Induced c-Fos and Nuclear Factor of Activated T Cells (NFAT) c1 Expression
-
- Kwak Han Bok
- Department of Anatomy, Wonkwang University
-
- Kim Hun Soo
- Department of Pathology, Wonkwang University
-
- Lee Myeung Su
- Department of Rheumatology, Wonkwang University
-
- Kim Kwang-Jin
- Department of Anatomy, Wonkwang University
-
- Choi Eun-Yong
- Department of Anatomy, Wonkwang University
-
- Choi Min-Kyu
- Department of Anatomy, Wonkwang University
-
- Kim Jeong-Joong
- Department of Anatomy, Wonkwang University
-
- Cho Hae Joong
- Department of Obstetrics and Gynecology, Wonkwang University
-
- Kim Jeong Woo
- Department of Orthopaedic Surgery, Wonkwang University
-
- Bae Ji-Myung
- Department of Dental Biomaterials, School of Dentistry, Wonkwang University
-
- Kim Yun-Kyung
- Department of Oriental Pharmacy, School of Pharmacy, Wonkwang University
-
- Park Byoung Hyun
- Department of Endocrinology, School of Medicine, Wonkwang University
-
- Ha Hyunil
- Department of Anatomy, Wonkwang University
-
- Chun Churl Hong
- Department of Orthopaedic Surgery, Wonkwang University
-
- Oh Jaemin
- Department of Anatomy, Wonkwang University
Bibliographic Information
- Other Title
-
- Pyridone 6, A pan-Janus-activated kinase inhibitor, suppresses osteoclast formation and bone resorption through down-regulation of receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL) induced c-Fos and nuclear factor of activated T cells (NFAT) c1 expression
- Pyridone 6 A pan Janus activated kinase inhibitor suppresses osteoclast formation and bone resorption through down regulation of receptor activator of nuclear factor kB NF kB ligand RANKL induced c Fos and nuclear factor of activated T cells NFAT c1 expression
Search this article
Abstract
It has been reported that Janus tyrosine kinase (JAK)-dependent signaling pathways play a critical role in the pathogenesis of numerous malignancies and immune reactions, and inhibition of JAK has been implicated in cell growth inhibition. The role which JAK has on osteoclast differentiation and anti-bone resorptive activity is not well understood. In this study, we investigated the effects of a pan-JAK inhibitor, pyridone 6, on osteoclast differentiation and bone-resorption in vitro and ex vivo. Pyridone 6 inhibited osteoclast differentiation in mouse bone marrow macrophage (BMM) cultures stimulated by the receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL) and co-cultures of bone marrow cells and osteoblasts. Pyridone 6 suppressed the expression of c-Fos and nuclear factor of activated T cells (NFAT) c1 in BMMs. It also inhibited the bone resorptive activity of mature osteoclasts that was accompanied by disruption of actin rings. Pyridone 6 also suppressed I-κB degradation and extracellular signal-regulated kinase (ERK) in mature osteoclasts, suggesting that these are the key molecules that pyridone 6 targets in the inhibition of osteoclast function. These results demonstrate inhibition of JAK may be useful for the treatment of bone-resorptive diseases, such as osteoporosis.
Journal
-
- Biological and Pharmaceutical Bulletin
-
Biological and Pharmaceutical Bulletin 32 (1), 45-50, 2009
The Pharmaceutical Society of Japan
- Tweet
Keywords
Details 詳細情報について
-
- CRID
- 1390282679602080128
-
- NII Article ID
- 110007021740
-
- NII Book ID
- AA10885497
-
- ISSN
- 13475215
- 09186158
-
- NDL BIB ID
- 9749519
-
- Text Lang
- en
-
- Data Source
-
- JaLC
- NDL
- Crossref
- CiNii Articles
-
- Abstract License Flag
- Disallowed