| Title | Interleukin-21 promotes osteoclastogenesis in RAW264.7 cells through the PI3K/AKT signaling pathway independently of RANKL |
| Authors | Xing, Rui Zhang, Yingjian Li, Changhong Sun, Lin Yang, Lin Zhao, Jinxia Liu, Xiangyuan |
| Affiliation | Peking Univ, Dept Rheumatol & Immunol, Hosp 3, 49 North Garden Rd, Beijing 100191, Peoples R China. |
| Keywords | rheumatoid arthritis interleukin-21 osteoclastogenesis AKT RAW264 7 cells RHEUMATOID-ARTHRITIS RECEPTOR IL-21 PROLIFERATION FIBROBLASTS DISEASE NK |
| Issue Date | 2016 |
| Publisher | INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE |
| Citation | INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE.2016,38(4),1125-1134. |
| Abstract | Cytokines play a key role in the bone destruction of rheumatoid arthritis (RA). Interleukin-21 (IL-21) promotes osteoclastogenesis in RA in a receptor activator of nuclear factor-B ligand (RANKL)-dependent way. Whether IL-21 is capable of promoting osteoclastogenesis directly in the absence of RANKL remains unknown. In the present study, we examined the osteoclastogenic activity of IL-21 in RAW264.7 cells in the absence of RANKL. We found that IL-21 enhanced osteoclastogenesis and this was demonstrated by increased numbers of tartrate-resistant acid phosphatase (TRAP)-positive stained, multinucleated cells compared with the negative control. Western blot analysis and immunocytochemistry showed the positive expression of calcitonin receptor (CTR) in the IL-21 group. RT-PCR and RT-qPCR also verified the increased mRNA expression of CTR and cathepsin K in the IL-21 group compared with the negative control. The scanning electronic microscope images showed a few resorption pits on the bone slices cultured with IL-21. The phosphoinositide 3-kinase (PI3K)/AKT pathway inhibitor LY294002 significantly suppressed IL-21-induced osteoclastogenesis. Taken together, these findings suggest that IL-21 has direct osteoclastogenic potential independently of RANKL. IL-21 may promote osteoclastogenesis through the PI3K/AKT signaling pathway. Therapy targeting IL-21 may be of value in preventing bone erosions in patients with RA. |
| URI | http://hdl.handle.net/20.500.11897/492988 |
| ISSN | 1107-3756 |
| DOI | 10.3892/ijmm.2016.2722 |
| Indexed | SCI(E) PubMed |
| Appears in Collections: | 第三医院 |
