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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2021-05-20

AUTHORS

Jae-Young Park, Hyun Cheol Bae, Sung Hee Pyo, Myung Chul Lee, Hyuk-Soo Han

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. More... »

PAGES

831-840

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s13770-021-00342-3

DOI

http://dx.doi.org/10.1007/s13770-021-00342-3

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https://app.dimensions.ai/details/publication/pub.1138209365

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/34014552


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