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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 저널정보
- 충북대학교 동물의학연구소 Journal of Biomedical and Translational Research Journal of Biomedical and Translational Research 제16권 제2호
- 발행연도
- 2015.1
- 수록면
- 35 - 39 (5page)
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Osteoclasts originated from hematopoietic stem cells are multi-nucleated cells that can resorb the bone matrix. Receptor activator of nuclear factor kappa-B (RANK)/RANK ligand (RANKL) signaling pathway is crucial for the differentiation and activation of osteoclasts. In this study, we investigated for the first time whether or not RANKL induced mitogen- and stress-activated kinase 1 (MSK1) phosphorylation at Ser 376. Activation of MSK1 was detected as soon as 5 min after RANKL stimulation and sparsely detected at 30 min after stimulation. RANKL-induced MSK1 phosphorylation occurred in a dose-dependent manner. MSK1 is known as a downstream signaling molecule of cAMP-dependent protein kinase (PKA). Treatment with the PKA inhibitor H89 significantly suppressed c-Fos and nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1) induction upon RANKL stimulation. In addition, cAMP response element-binding protein (CREB) phosphorylation was extremely inhibited by H89 treatment. Mitogen-activated protein kinases (MAPKs) have been investigated for induction of MSK1 phosphorylation. Specific signaling pathway inhibitors for p38 and extracellular signal-regulated kinases (ERKs) significantly blocked RANKL-induced MSK1 activation. Finally, as a downstream effector of the p38-MSK1 pathway, c-Fos transcriptional activity was determined. RANKL-mediated elevation of c-Fos transcriptional activity was significantly suppressed by p38 inhibitor. Moreover, a dominant negative form of CREB suppressed activation of NFATc1. In conclusion, RANKL-stimulated MSK1 phosphorylation could play a role in induction of NFATc1 through CREB and c-Fos activation as a downstream molecule of p38, ERK MAPKs, and PKA. Our results support basic information for the development of osteoclast specific inhibitors.
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참고문헌 (21)
참고문헌 신청
Boyle WJ / 2003 / Osteoclast differentiation and activation / Nature 423 : 337 ~ 342
Chang EJ / 2007 / Hyaluronan inhibits osteoclast differentiation via Toll-like receptor 4 / J Cell Sci 120 : 166 ~ 176
Chang EJ / 2008 / The JNK-dependent CaMK pathway restrains the reversion of committed cells during osteoclast differentiation / J Cell Sci 121 : 2555 ~ 2564
Corral DA / 1998 / Dissociation between bone resorption and bone formation in osteopenic transgenic mice / Proc Natl Acad Sci USA 95 : 13835 ~ 13840
Delghandi MP / 2005 / The cAMP signalling pathway activates CREB through PKA, p38 and MSK1 in NIH 3T3 cells / Cell Signal 17 : 1343 ~ 1351
Chang EJ / 2007 / Hyaluronan inhibits osteoclast differentiation via Toll-like receptor 4 / J Cell Sci 120 : 166 ~ 176
Chang EJ / 2008 / The JNK-dependent CaMK pathway restrains the reversion of committed cells during osteoclast differentiation / J Cell Sci 121 : 2555 ~ 2564
Corral DA / 1998 / Dissociation between bone resorption and bone formation in osteopenic transgenic mice / Proc Natl Acad Sci USA 95 : 13835 ~ 13840
Delghandi MP / 2005 / The cAMP signalling pathway activates CREB through PKA, p38 and MSK1 in NIH 3T3 cells / Cell Signal 17 : 1343 ~ 1351
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