Gallotannin attenuates 2‑deoxy‑D‑glucose‑induced dedifferentiation and endoplasmic reticulum stress through inhibition of inositol‑requiring enzyme 1 downstream p38 kinase pathway in chondrocytes

  • Authors:
    • Su Min Kim
    • Yohan Han
    • Seon‑Mi Yu
    • Song Ja Kim
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  • Published online on: October 25, 2019     https://doi.org/10.3892/mmr.2019.10773
  • Pages: 5249-5256
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Abstract

Gallotannin (GT) is a class of polyphenols with antioxidant, anticancer, and antiviral activities. 2‑Deoxy‑D‑glucose (2DG), a glucose‑derived molecule, can inhibit glucose metabolism and induce endoplasmic reticulum (ER) stress. GT in primary‑cultured chondrocytes enhances expression of type II collagen, an indicator of differentiation, and cyclooxygenase‑2 (COX‑2), which mediates inflammatory reactions. In contrast, 2DG reduces type II collagen and COX‑2 expression while driving ER‑stress‑induced unglycosylation. In the present study, it was investigated whether GT could attenuate 2DG‑induced dedifferentiation and ER‑stress. Following treatment with GT and 2DG, chondrocytes were assessed using western blotting, RT‑PCR, immunofluorescence, and alcian blue staining. GT restored type II collagen expression that was reduced by 2DG, inhibited ER‑stress‑induced COX‑2 unglycosylation, and induced COX‑2 expression. The expression of a glucose‑regulated protein, GRP78, which is an indicator of reduced ER‑stress, was decreased. To link the GT signaling pathway with pathways that inhibit 2DG‑induced dedifferentiation and ER‑stress, inhibitors were treated in chondrocytes. The results revealed that, among the different signaling pathways triggered by ER‑stress, the p38 kinase pathway was involved in the inositol‑requiring enzyme 1 (IRE1) downstream signaling pathway. Following inhibition of the IRE1 pathway, type II collagen expression was increased and COX‑2 expression was decreased. In addition, after examining the splicing of X‑box binding protein 1 (XBP‑1) which is dependent on IRE1 activation induced by ER‑stress, it was revealed that GT inhibited the increase of XBP‑1s after splicing due to 2DG‑induced ER stress. GT in chondrocytes inhibited 2DG‑induced dedifferentiation and ER‑stress‑induced COX‑2 unglycosylation while regulating differentiation and inflammation via the ER‑stress‑induced p38 kinase pathway downstream from the IRE1 pathway.
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December-2019
Volume 20 Issue 6

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Kim SM, Han Y, Yu SM and Kim SJ: Gallotannin attenuates 2‑deoxy‑D‑glucose‑induced dedifferentiation and endoplasmic reticulum stress through inhibition of inositol‑requiring enzyme 1 downstream p38 kinase pathway in chondrocytes. Mol Med Rep 20: 5249-5256, 2019
APA
Kim, S.M., Han, Y., Yu, S., & Kim, S.J. (2019). Gallotannin attenuates 2‑deoxy‑D‑glucose‑induced dedifferentiation and endoplasmic reticulum stress through inhibition of inositol‑requiring enzyme 1 downstream p38 kinase pathway in chondrocytes. Molecular Medicine Reports, 20, 5249-5256. https://doi.org/10.3892/mmr.2019.10773
MLA
Kim, S. M., Han, Y., Yu, S., Kim, S. J."Gallotannin attenuates 2‑deoxy‑D‑glucose‑induced dedifferentiation and endoplasmic reticulum stress through inhibition of inositol‑requiring enzyme 1 downstream p38 kinase pathway in chondrocytes". Molecular Medicine Reports 20.6 (2019): 5249-5256.
Chicago
Kim, S. M., Han, Y., Yu, S., Kim, S. J."Gallotannin attenuates 2‑deoxy‑D‑glucose‑induced dedifferentiation and endoplasmic reticulum stress through inhibition of inositol‑requiring enzyme 1 downstream p38 kinase pathway in chondrocytes". Molecular Medicine Reports 20, no. 6 (2019): 5249-5256. https://doi.org/10.3892/mmr.2019.10773