Journal
TISSUE ENGINEERING AND REGENERATIVE MEDICINE
Volume 18, Issue 5, Pages 831-840Publisher
KOREAN TISSUE ENGINEERING REGENERATIVE MEDICINE SOC
DOI: 10.1007/s13770-021-00342-3
Keywords
TGF-β Transglutaminase-2; Articular chondrocyte; Cartilage; Catabolism
Categories
Funding
- Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Science [NRF-2015R1D1A1A01059785]
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By investigating the interplay between TGF beta 1 and TG2 in chondrocytes, it was found that TGF beta 1 can promote chondrocyte catabolism in osteoarthritis through TG2 mediation, leading to cartilage degeneration.
Background: Transforming growth factor beta 1 (TGF beta 1) plays an essential role in maintaining cartilage homeostasis. TGF beta 1 is known to upregulate anabolic processes in articular cartilage, but the role of TGF beta 1 in chondrocyte catabolism remains unclear. Thus, we examined whether TGF beta 1 increases catabolic processes in the osteoarthritic joint via transglutaminase 2 (TG2). In this study, we investigated whether interplay between TGF beta 1 and TG2 mediates chondrocyte catabolism and cartilage degeneration in osteoarthritis. Methods: To investigate the role of TGF beta 1 and TG2 in osteoarthritis, we performed immunostaining to measure the levels of TGF beta 1 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 TGF beta 1 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 TGF beta 1 and TG2 in human osteoarthritic cartilage compared with non-osteoarthritic cartilage. TGF beta 1 treatment significantly increased the expression of TG2 via p38 and ERK activation. TGF beta 1-induced TG2 also elevated the level of MMP-13 and type X collagen via NF-kappa B activation in chondrocytes. Cartilage damage after ACLT and DMM surgery was less severe in TG2 knock-out mice compared with wild-type mice. Conclusion: TGF beta 1 modulated catabolic processes in chondrocytes in a TG2-dependent manner. TGF beta 1-induced TG2 might be the therapeutic target for treating cartilage degeneration and osteoarthritis.
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