| Title | RANKL downregulates cell surface CXCR6 expression through JAK2/STAT3 signaling pathway during osteoclastogenesis |
| Authors | Li, Changhong Zhao, Jinxia Sun, Lin Yao, Zhongqiang Liu, Rui Huang, Jiansheng Liu, Xiangyuan |
| Affiliation | Peking Univ, Dept Rheumatol & Immunol, Hosp 3, Beijing 100191, Peoples R China. Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA. |
| Keywords | RANKL Osteoclastogenesis CXCR6 CXCL16 JAK2/STAT3 RECEPTOR ACTIVATOR NUCLEAR-FACTOR IN-VITRO KEY ROLE CHEMOKINE LIGAND DIFFERENTIATION CANCER METASTASIS MODULATION |
| Issue Date | 2012 |
| Publisher | 生物化学与生物物理学研究通讯 |
| Citation | BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS.2012,429,(3-4),156-162. |
| Abstract | The receptor activator of nuclear factor-kappa B ligand (RANKL), as a member of the tumor necrosis factor (TNF) family, plays an essential role in osteoclast differentiation and function. Chemokines and their receptors have recently been shown to play critical roles in osteoclastogenesis, however, whether CXCL16-CXCR6 plays role in RANKL-mediated osteoclastogenesis is unknown. In this study, we first reported that RANKL decreased CXCR6 in a dose-dependent manner, which may be through deactivation of Akt and STAT3 signaling induced by CXCL16. Interestingly, RANKL-mediated CXCR6 reduction may be associated to the activation of STAT3 by phosphorylation. When STAT3 activation was blocked by JAK2/STAT3 inhibitor AG490, RANKL failed to shut down CXCR6 expression during osteoclastogenesis. However, CXCL16 alone did not augment RANKL-mediated osteoclast differentiation and did not alter RANKL-receptor RANK mRNA expression. These results demonstrate that reduction of CXCL16-CXCR6 is critical in RANKL-mediated osteoclastogenesis, which is mainly through the activation of JAK2/STAT3 signaling. CXCL16-CXCR6 axis may become a novel target for the therapeutic intervention of bone resorbing diseases such as rheumatoid arthritis and osteoporosis. (C) 2012 Elsevier Inc. All rights reserved. |
| URI | http://hdl.handle.net/20.500.11897/190718 |
| ISSN | 0006-291X |
| DOI | 10.1016/j.bbrc.2012.10.122 |
| Indexed | SCI(E) PubMed |
| Appears in Collections: | 第三医院 |
