MSK1 regulates RANKL-induced NFATc1 expression through CREB and c-Fos / 동물의과학연구지

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.

Effects of Symptom Severity and Symptom Interference on Sleep Disturbance in Cancer Patients

PURPOSE: The purpose of this study was conducted to identify the impact of Symptom Severity and Symptom Interference on Sleep Disturbance among cancer patients. METHODS: This study was conducted from October 8th to October 25th, 2012. One hundred eight cancer patients were recruited from S city in Korea. The instruments used in this study were the Symptom Severity, Symptom Interference and the Sleep Disturbance scales for patients with cancer. Data were analyzed using descriptive statistics, t-test, ANOVA, Pearson correlation coefficients and multiple regression with the SPSS/WIN 20.0 program. RESULTS: The Sleep Disturbance for cancer patients showed a significant relationship with Symptom Interference and cancer stage. The significant factors influencing Sleep Disturbance were Symptom Severity and Symptom Interference. They explained 40.5% of the variance in stage IV. CONCLUSION: Patients with cancer experienced Symptom Severity and Symptom Interference which led to a negative effect on Sleep Disturbance. The results suggest that intervention programs to reduce Symptom Severity, Symptom Interference could improve Sleep Disturbance for cancer patients.