Transcription Factor EGR1 Directs Tendon Differentiation and Promotes Tendon Repair

Overview

Journal J Clin Invest

Specialty General Medicine

Date 2013 Jul 19

PMID 23863709

Citations 121

Authors

Marie-Justine Guerquin

Benjamin Charvet

Geoffroy Nourissat

Emmanuelle Havis

Olivier Ronsin

Marie-Ange Bonnin

Mathilde Ruggiu

Isabel Olivera-Martinez

Nicolas Robert

Yinhui Lu

Karl E Kadler

Tristan Baumberger

Levon Doursounian

Francis Berenbaum

Delphine Duprez

Affiliations

Soon will be listed here.

Abstract

Tendon formation and repair rely on specific combinations of transcription factors, growth factors, and mechanical parameters that regulate the production and spatial organization of type I collagen. Here, we investigated the function of the zinc finger transcription factor EGR1 in tendon formation, healing, and repair using rodent animal models and mesenchymal stem cells (MSCs). Adult tendons of Egr1-/- mice displayed a deficiency in the expression of tendon genes, including Scx, Col1a1, and Col1a2, and were mechanically weaker compared with their WT littermates. EGR1 was recruited to the Col1a1 and Col2a1 promoters in postnatal mouse tendons in vivo. Egr1 was required for the normal gene response following tendon injury in a mouse model of Achilles tendon healing. Forced Egr1 expression programmed MSCs toward the tendon lineage and promoted the formation of in vitro-engineered tendons from MSCs. The application of EGR1-producing MSCs increased the formation of tendon-like tissues in a rat model of Achilles tendon injury. We provide evidence that the ability of EGR1 to promote tendon differentiation is partially mediated by TGF-β2. This study demonstrates EGR1 involvement in adult tendon formation, healing, and repair and identifies Egr1 as a putative target in tendon repair strategies.

Citing Articles

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