TGFβ1-Induced Transglutaminase-2 Triggers Catabolic Response in Osteoarthritic Chondrocytes by Modulating MMP-13

Abstract

Background:

Transforming growth factor beta 1 (TGFβ1) plays an essential role in maintaining cartilage homeostasis. TGFβ1 is known to upregulate anabolic processes in articular cartilage, but the role of TGFβ1 in chondrocyte catabolism remains unclear. Thus, we examined whether TGFβ1 increases catabolic processes in the osteoarthritic joint via transglutaminase 2 (TG2). In this study, we investigated whether interplay between TGFβ1 and TG2 mediates chondrocyte catabolism and cartilage degeneration in osteoarthritis.

Methods:

To investigate the role of TGFβ1 and TG2 in osteoarthritis, we performed immunostaining to measure the levels of TGFβ1 and TG2 in 6 human non-osteoarthritic and 16 osteoarthritic joints. We conducted quantitative reverse transcription polymerase chain reaction and western blot analysis to investigate the relationship between TGFβ1 and TG2 in chondrocytes and determined whether TG2 regulates the expressions of matrix metalloproteinase (MMP)-13, type II, and type X collagen. We also examined the extent of cartilage degradation after performing anterior cruciate ligament transection (ACLT) and destabilization of the medial meniscus (DMM) surgery in TG2 knock-out mice.

Results:

We confirmed the overexpression of TGFβ1 and TG2 in human osteoarthritic cartilage compared with non-osteoarthritic cartilage. TGFβ1 treatment significantly increased the expression of TG2 via p38 and ERK activation. TGFβ1-induced TG2 also elevated the level of MMP-13 and type X collagen via NF-κB activation in chondrocytes. Cartilage damage after ACLT and DMM surgery was less severe in TG2 knock-out mice compared with wild-type mice.

Conclusion:

TGFβ1 modulated catabolic processes in chondrocytes in a TG2-dependent manner. TGFβ1-induced TG2 might be the therapeutic target for treating cartilage degeneration and osteoarthritis.

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Acknowledgements

The authors would like to thank Professor In-Gyu Kim for his helpful comments and discussions and for also providing TG2 KO mice. This study was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Science (NRF-2015R1D1A1A01059785).

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Correspondence to Hyuk-Soo Han.

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This research has been approved by the IRB of Seoul National University Hospital. (IRB No. 1510-077-711).

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Park, JY., Bae, H.C., Pyo, S.H. et al. TGFβ1-Induced Transglutaminase-2 Triggers Catabolic Response in Osteoarthritic Chondrocytes by Modulating MMP-13. Tissue Eng Regen Med (2021). https://doi.org/10.1007/s13770-021-00342-3

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Keywords

  • TGF-β
  • Transglutaminase-2
  • Articular chondrocyte
  • Cartilage
  • Catabolism