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Interleukin-21 promotes osteoclastogenesis in RAW264.7 cells through the PI3K/AKT signaling pathway independently of RANKL

  • Authors:
    • Rui Xing
    • Yingjian Zhang
    • Changhong Li
    • Lin Sun
    • Lin Yang
    • Jinxia Zhao
    • Xiangyuan Liu
  • View Affiliations / Copyright

    Affiliations: Department of Rheumatology and Immunology, Peking University Third Hospital, Beijing 100191, P.R. China
    Copyright: © Xing et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1125-1134
    |
    Published online on: August 30, 2016
       https://doi.org/10.3892/ijmm.2016.2722
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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-κB 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.
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Copy and paste a formatted citation
Spandidos Publications style
Xing R, Zhang Y, Li C, Sun L, Yang L, Zhao J and Liu X: Interleukin-21 promotes osteoclastogenesis in RAW264.7 cells through the PI3K/AKT signaling pathway independently of RANKL. Int J Mol Med 38: 1125-1134, 2016.
APA
Xing, R., Zhang, Y., Li, C., Sun, L., Yang, L., Zhao, J., & Liu, X. (2016). Interleukin-21 promotes osteoclastogenesis in RAW264.7 cells through the PI3K/AKT signaling pathway independently of RANKL. International Journal of Molecular Medicine, 38, 1125-1134. https://doi.org/10.3892/ijmm.2016.2722
MLA
Xing, R., Zhang, Y., Li, C., Sun, L., Yang, L., Zhao, J., Liu, X."Interleukin-21 promotes osteoclastogenesis in RAW264.7 cells through the PI3K/AKT signaling pathway independently of RANKL". International Journal of Molecular Medicine 38.4 (2016): 1125-1134.
Chicago
Xing, R., Zhang, Y., Li, C., Sun, L., Yang, L., Zhao, J., Liu, X."Interleukin-21 promotes osteoclastogenesis in RAW264.7 cells through the PI3K/AKT signaling pathway independently of RANKL". International Journal of Molecular Medicine 38, no. 4 (2016): 1125-1134. https://doi.org/10.3892/ijmm.2016.2722
Copy and paste a formatted citation
x
Spandidos Publications style
Xing R, Zhang Y, Li C, Sun L, Yang L, Zhao J and Liu X: Interleukin-21 promotes osteoclastogenesis in RAW264.7 cells through the PI3K/AKT signaling pathway independently of RANKL. Int J Mol Med 38: 1125-1134, 2016.
APA
Xing, R., Zhang, Y., Li, C., Sun, L., Yang, L., Zhao, J., & Liu, X. (2016). Interleukin-21 promotes osteoclastogenesis in RAW264.7 cells through the PI3K/AKT signaling pathway independently of RANKL. International Journal of Molecular Medicine, 38, 1125-1134. https://doi.org/10.3892/ijmm.2016.2722
MLA
Xing, R., Zhang, Y., Li, C., Sun, L., Yang, L., Zhao, J., Liu, X."Interleukin-21 promotes osteoclastogenesis in RAW264.7 cells through the PI3K/AKT signaling pathway independently of RANKL". International Journal of Molecular Medicine 38.4 (2016): 1125-1134.
Chicago
Xing, R., Zhang, Y., Li, C., Sun, L., Yang, L., Zhao, J., Liu, X."Interleukin-21 promotes osteoclastogenesis in RAW264.7 cells through the PI3K/AKT signaling pathway independently of RANKL". International Journal of Molecular Medicine 38, no. 4 (2016): 1125-1134. https://doi.org/10.3892/ijmm.2016.2722
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