Publication: Induction of high temperature requirement A1, a serine protease, by TGF-beta1 in articular chondrocytes of mouse models of OA
Authors
Xu, Lin ; Golshirazian, Imanoel ; Asbury, Brian J. ; Li, Yefu
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Publisher
F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología
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DOI
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info:eu-repo/semantics/article
Description
Abstract
The goal of this study is to determine
whether transforming growth factor beta 1 (Tgf-ß1)
induces the high temperature requirement A1 (HtrA1) in
articular chondrocytes of two mouse models of
osteoarthritis (OA). Early onset articular cartilage
degeneration in the mouse models was characterized by
histology. Expression profiles of Tgf-ß1, p-Smad1, pSmad2/3
and HtrA1 in knee joints of the mouse models
were examined by immunofluorescene. By in vitro and
ex vivo experiments, human primary chondrocytes and
articular cartilages from femoral condyles of mice were
treated with recombinant human TGF-ß1 and an ALK5
chemical inhibitor, SB431542. The level of HTRA1
mRNA in human and mouse articular chondrocytes was
examined by real-time PCR. Chondrocyte clusters were
present in the articular cartilage of knee joints in the
mouse models. Increased expressions of Tgf-ß1, pSmad2/3
and HtrA1 were detected in the articular
chondrocyte of knee joints in the mouse models. The
increased expressions of p-Smad2/3 and HtrA1 were colocalized
in the articular chondrocyte of the knee joints.
The expression of p-Smad1 was hardly detectable in the
mouse models and their corresponding wild-type
littermates. The level of HTRA1 mRNA was increased
in human and mouse articular chondrocytes treated with
TGF-ß1, compared with that in chondrocytes without the
treatment of TGF-ß1. The TGF-ß1-induced expression
of HTRA1 in human and mouse articular chondrocytes
was inhibited by SB431542. These results suggest that
the Tgf-ß1 canonical signaling was activated to induce
HtrA1 in the articular chondrocytes of the mouse models
of OA.
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Citation
Histology and Histopathology, vol. 29, nº 5, (2014)
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