KMID : 1377020210180050831
|
|
Tissue Engineering and Regenerative Medicine 2021 Volume.18 No. 5 p.831 ~ p.840
|
|
TGF¥â1-Induced Transglutaminase-2 Triggers Catabolic Response in Osteoarthritic Chondrocytes by Modulating MMP-13
|
|
Park Jae-Young
Bae Hyun-Cheol Pyo Sung-Hee Lee Myung-Chul Han Hyuk-Soo
|
|
Abstract
|
|
|
Background: Transforming growth factor beta 1 (TGF¥â1) plays an essential role in maintaining cartilage homeostasis. TGF¥â1 is known to upregulate anabolic processes in articular cartilage, but the role of TGF¥â1 in chondrocyte catabolism remains unclear. Thus, we examined whether TGF¥â1 increases catabolic processes in the osteoarthritic joint via transglutaminase 2 (TG2). In this study, we investigated whether interplay between TGF¥â1 and TG2 mediates chondrocyte catabolism and cartilage degeneration in osteoarthritis.
Methods: To investigate the role of TGF¥â1 and TG2 in osteoarthritis, we performed immunostaining to measure the levels of TGF¥â1 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¥â1 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¥â1 and TG2 in human osteoarthritic cartilage compared with non-osteoarthritic cartilage. TGF¥â1 treatment significantly increased the expression of TG2 via p38 and ERK activation. TGF¥â1-induced TG2 also elevated the level of MMP-13 and type X collagen via NF-¥êB 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¥â1 modulated catabolic processes in chondrocytes in a TG2-dependent manner. TGF¥â1-induced TG2 might be the therapeutic target for treating cartilage degeneration and osteoarthritis.
|
|
KEYWORD
|
|
TGF-¥â, Transglutaminase-2, Articular chondrocyte, Cartilage, Catabolism
|
|
FullTexts / Linksout information
|
|
|
|
Listed journal information
|
|
|