Cell autonomous TGFβ signaling is essential for stem/progenitor cell recruitment into degenerative tendons.

Autor:	Tan GK; Research Division, Shriners Hospital for Children, Portland, OR 97239, USA; Department of Orthopaedics and Rehabilitation, School of Medicine, Oregon Health & Science University, Portland, OR 97239, USA. Electronic address: tagu@ohsu.edu., Pryce BA; Research Division, Shriners Hospital for Children, Portland, OR 97239, USA., Stabio A; Research Division, Shriners Hospital for Children, Portland, OR 97239, USA., Keene DR; Research Division, Shriners Hospital for Children, Portland, OR 97239, USA., Tufa SF; Research Division, Shriners Hospital for Children, Portland, OR 97239, USA., Schweitzer R; Research Division, Shriners Hospital for Children, Portland, OR 97239, USA; Department of Orthopaedics and Rehabilitation, School of Medicine, Oregon Health & Science University, Portland, OR 97239, USA. Electronic address: schweitz@ohsu.edu.
Jazyk:	angličtina
Zdroj:	Stem cell reports [Stem Cell Reports] 2021 Dec 14; Vol. 16 (12), pp. 2942-2957. Date of Electronic Publication: 2021 Nov 24.
DOI:	10.1016/j.stemcr.2021.10.018
Abstrakt:	Understanding cell recruitment in damaged tendons is critical for improvements in regenerative therapy. We recently reported that targeted disruption of transforming growth factor beta (TGFβ) type II receptor in the tendon cell lineage (Tgfbr2 ScxCre ) resulted in resident tenocyte dedifferentiation and tendon deterioration in postnatal stages. Here we extend the analysis and identify direct recruitment of stem/progenitor cells into the degenerative mutant tendons. Cre-mediated lineage tracing indicates that these cells are not derived from tendon-ensheathing tissues or from a Scleraxis-expressing lineage, and they turned on tendon markers only upon entering the mutant tendons. Through immunohistochemistry and inducible gene deletion, we further find that the recruited cells originated from a Sox9-expressing lineage and their recruitment was dependent on cell autonomous TGFβ signaling. The cells identified in this study thus differ from previous reports of cell recruitment into injured tendons and suggest a critical role for TGFβ signaling in cell recruitment, providing insights that may support improvements in tendon repair. (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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