Postnatal Tendon Growth and Remodeling Requires Platelet-Derived Growth Factor Receptor Signaling

Abstract

Platelet-derived growth factor receptor (PDGFR) signaling plays an important role in the fundamental biological activities of many cells that compose musculoskeletal tissues. However, little is known about the role of PDGFR signaling during tendon growth and remodeling in adult animals. Using the hindlimb synergist ablation model of tendon growth, our objectives were to determine the role of PDGFR signaling in the adaptation of tendons subjected to a mechanical growth stimulus, as well as to investigate the biological mechanisms behind this response. We demonstrate that both PDGFRs, PDGFRα and PDGFRβ, are expressed in tendon fibroblasts, and that the inhibition of PDGFR signaling suppresses the normal growth of tendon tissue in response to mechanical growth cues due to defects in fibroblast proliferation and migration. We also identify that membrane type-1 matrix metalloproteinase (MT1-MMP) as an essential proteinase for the migration of tendon fibroblasts through their extracellular matrix. Furthermore, we report that MT1-MMP translation is regulated by PI3K/Akt signaling , while ERK1/2 controls post-translational trafficking of MT1-MMP to the plasma membrane of tendon fibroblasts. Taken together, these findings demonstrate that PDGFR signaling is necessary for postnatal tendon growth and remodeling, and that MT1-MMP is a critical mediator of tendon fibroblast migration and a potential target for the treatment of tendon injuries and diseases. KEYWORDSMatrix metalloproteinase; extracellular matrix; fibroblast; plated-derived growth factor receptor; tenocyte.peer-reviewed)

The impact of loading, unloading, ageing and injury on the human tendon

“…; Sugg et al . ). In addition, insulin like growth factor‐I (IGF‐I) can also act as a link between mechanical load and collagen synthesis in tendon tissue (Hansson et al .…”

“…), and that the activation of ERK1/2 seems important for this MMP response (Sugg et al . ). Finally, an investigation of the breakdown products of collagen revealed a higher release of these in response to exercise and prolonged physical training (Langberg et al .…”