Downregulation of aquaporin 9 decreases catabolic factor expression through nuclear factor‑κB signaling ins chondrocytes

  • Authors:
    • Kazuhiro Takeuchi
    • Shinya Hayashi
    • Tomoyuki Matumoto
    • Shingo Hashimoto
    • Koji Takayama
    • Nobuaki Chinzei
    • Shinsuke Kihara
    • Masahiko Haneda
    • Shinsuke Kirizuki
    • Yuichi Kuroda
    • Masanori Tsubosaka
    • Kotaro Nishida
    • Ryosuke Kuroda
  • View Affiliations

  • Published online on: June 13, 2018     https://doi.org/10.3892/ijmm.2018.3729
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Abstract

Aquaporins (AQPs) are small integral membrane proteins that are essential for water transport across membranes. AQP9, one of the 13 mammalian AQPs (including AQP0 to 12), has been reported to be highly expressed in hydrarthrosis and synovitis patients. Given that several studies have identified signal transduction as an additional function of AQPs, it is hypothesized that AQP9 may modulate inflammatory signal transduction in chondrocytes. Therefore, the present study used a model of interleukin (IL)‑1β‑induced inflammation to determine the mechanisms associated with AQP9 functions in chondrocytes. Osteoarthritis (OA) and normal cartilage samples were subjected to immunohistological analysis. In addition, matrix metalloproteinase (MMP)3, MMP13 and a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS‑5) mRNA and protein analysis was conducted in normal human articular chondrocytes from the knee (NHAC‑Kn) stimulated with IL‑1β by reverse transcription‑polymerase chain reaction (RT‑qPCR) and western blotting, respectively. AQP9 knockdown was also performed by transfection of AQP9‑specific small interfering RNA using Lipofectamine. AQP1, 3, 7, 9 and 11 mRNA expression levels were detected in OA human chondrocytes and in IL‑1β‑treated normal human chondrocytes. The levels of AQP9, MMP‑3, MMP‑13 and ADAMTS‑5 mRNA were increased by treatment with 10 ng/ml IL‑1β in a time‑dependent manner, while knockdown of AQP9 expression significantly decreased the mRNA levels of the MMP3, MMP13 and ADAMTS‑5 genes, as well as the phosphorylation of IκB kinase (IKK). Treatment with a specific IKK inhibitor also significantly decreased the expression levels of MMP‑3, MMP‑13 and ADAMTS‑5 in response to IL‑1β stimulation. Furthermore, immunohistochemical analysis demonstrated that AQP9 and inflammatory markers were highly expressed in OA cartilage. In addition, the downregulation of AQP9 in cultured chondrocytes decreased the catabolic gene expression in response to IL‑1β stimulation through nuclear factor‑κB signaling. Therefore, AQP9 may be a promising target for the treatment of OA.

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APA
Takeuchi, K., Hayashi, S., Matumoto, T., Hashimoto, S., Takayama, K., Chinzei, N. ... Kuroda, R. (1899). Downregulation of aquaporin 9 decreases catabolic factor expression through nuclear factor‑κB signaling ins chondrocytes. International Journal of Molecular Medicine, 0, 0-0. https://doi.org/10.3892/ijmm.2018.3729
MLA
Takeuchi, K., Hayashi, S., Matumoto, T., Hashimoto, S., Takayama, K., Chinzei, N., Kihara, S., Haneda, M., Kirizuki, S., Kuroda, Y., Tsubosaka, M., Nishida, K., Kuroda, R."Downregulation of aquaporin 9 decreases catabolic factor expression through nuclear factor‑κB signaling ins chondrocytes". International Journal of Molecular Medicine 0.0 (1899): 0-0.
Chicago
Takeuchi, K., Hayashi, S., Matumoto, T., Hashimoto, S., Takayama, K., Chinzei, N., Kihara, S., Haneda, M., Kirizuki, S., Kuroda, Y., Tsubosaka, M., Nishida, K., Kuroda, R."Downregulation of aquaporin 9 decreases catabolic factor expression through nuclear factor‑κB signaling ins chondrocytes". International Journal of Molecular Medicine 0, no. 0 (1899): 0-0. https://doi.org/10.3892/ijmm.2018.3729