Open AccessWnt/β-catenin signaling suppresses expressions of Scx, Mkx, and Tnmd in tendon-derived cells
Author(s) -
Yasuzumi Kishimoto,
Bisei Ohkawara,
Tadahiro Sasajima,
Mikako Ito,
Akio Matsubara,
Naoki Ishiguro,
Chisa Shukunami,
Denitsa Docheva,
Kinji Ohno
Publication year - 2017
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0182051
Subject(s) - wnt signaling pathway , tendon , microbiology and biotechnology , signal transduction , downregulation and upregulation , catenin , beta catenin , biology , anatomy , gene , genetics
After tendon injuries, biomechanical properties of the injured tendon are not fully recovered in most cases. Modulation of signaling pathways, which are involved in tendon development and tendon repair, is one of attractive modalities to facilitate proper regeneration of the injured tendon. The roles of TGF-β signaling in tendon homeostasis and tendon development have been elucidated. In contrast, the roles of Wnt/β-catenin signaling in tendon remain mostly elusive. We found that the number of β-catenin-positive cells was increased at the injured site, suggesting involvement of Wnt/β-catenin signaling in tendon healing. Activation of Wnt/β-catenin signaling suppressed expressions of tenogenic genes of Scx , Mkx , and Tnmd in rat tendon-derived cells (TDCs) isolated from the Achilles tendons of 6-week old rats. Additionally, activation of Wnt/β-catenin reduced the amounts of Smad2 and Smad3, which are intracellular mediators for TGF-β signaling, and antagonized upregulation of Scx induced by TGF-β signaling in TDCs. We found that Wnt/β-catenin decreased Mkx and Tnmd expressions without suppressing Scx expression in Scx -programmed tendon progenitors. Our studies suggest that Wnt/β-catenin signaling is a repressor for tenogenic gene expressions.