Abstract
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.
Highlights
Tendon injuries, due to degeneration with aging or overuse, are frequently observed in clinical settings and remain a challenge in orthopedic trauma [1]
To evaluate the effects of Wnt/β-catenin signaling in tendon cells, tendon-derived cells (TDCs) were isolated from the Achilles tendon of 6-week-old male Sprague Dawley (SD) rats, and were treated with Wnt3a, BIO, and/or IWR
To investigate the effects of Wnt/β-catenin signaling and TGF-β1 signaling on tenogenic gene expressions in hMSC-Scx cells, we treated hMSC-Scx cells with activators and/or inhibitors used for TDCs (Figs 2 and 3)
Summary
Due to degeneration with aging or overuse, are frequently observed in clinical settings and remain a challenge in orthopedic trauma [1]. At the repairing site of injured tendon in dog, extracellular growth factors including transforming growth factor-beta (TGF-β), epithelial growth factor (EGF), platelet-derived growth factor (PDGF), insulin growth factor (IGF), basic fibroblast growth factor-2 (FGF2), and vascular endothelial growth factor (VEGF) are detected by immunohistochemical analysis [14] These growth factors are detected in injured tendons at the mRNA and protein levels in chick [15] and at the mRNA level in rabbit [16]. In primary cells isolated from adult rat tendon, activation of Wnt/β-catenin signaling reduces gene expressions of Scx, Mkx, and Tnmd. We propose that activation of Wnt/β-catenin signaling attenuates differentiation of tendon cells by suppressing gene expressions of Scx, Mkx, and Tnmd
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