Deletion of EP4 in S100a4-lineage cells reduces scar tissue formation during early but not later stages of tendon healing

Abstract Tendon injuries heal via scar tissue rather than regeneration. This healing response forms adhesions between the flexor tendons in the hand and surrounding tissues, resulting in impaired range of motion and hand function. Mechanistically, inflammation has been strongly linked to adhesion fo...

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Autores principales:	Jessica E. Ackerman, Katherine T. Best, Regis J. O’Keefe, Alayna E. Loiselle
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/930aa5bc24584e0e8f7273072e04ab6d
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spelling	oai:doaj.org-article:930aa5bc24584e0e8f7273072e04ab6d2021-12-02T11:40:58ZDeletion of EP4 in S100a4-lineage cells reduces scar tissue formation during early but not later stages of tendon healing10.1038/s41598-017-09407-72045-2322https://doaj.org/article/930aa5bc24584e0e8f7273072e04ab6d2017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-09407-7https://doaj.org/toc/2045-2322Abstract Tendon injuries heal via scar tissue rather than regeneration. This healing response forms adhesions between the flexor tendons in the hand and surrounding tissues, resulting in impaired range of motion and hand function. Mechanistically, inflammation has been strongly linked to adhesion formation, and Prostaglandin E2 (PGE2) is associated with both adhesion formation and tendinopathy. In the present study we tested the hypothesis that deletion of the PGE2 receptor EP4 in S100a4-lineage cells would decrease adhesion formation. S100a4-Cre; EP4 flox/flox (EP4cKOS100a4) repairs healed with improved gliding function at day 14, followed by impaired gliding at day 28, relative to wild type. Interestingly, EP4cKOS100a4 resulted in only transient deletion of EP4, suggesting up-regulation of EP4 in an alternative cell population in these mice. Loss of EP4 in Scleraxis-lineage cells did not alter gliding function, suggesting that Scx-lineage cells are not the predominant EP4 expressing population. In contrast, a dramatic increase in α-SMA+, EP4+ double-positive cells were observed in EP4cKOS100a4 suggesting that EP4cKOS100a4 repairs heal with increased infiltration of EP4 expressing α-SMA myofibroblasts, identifying a potential mechanism of late up-regulation of EP4 and impaired gliding function in EP4cKOS100a4 tendon repairs.Jessica E. AckermanKatherine T. BestRegis J. O’KeefeAlayna E. LoiselleNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jessica E. Ackerman Katherine T. Best Regis J. O’Keefe Alayna E. Loiselle Deletion of EP4 in S100a4-lineage cells reduces scar tissue formation during early but not later stages of tendon healing
description	Abstract Tendon injuries heal via scar tissue rather than regeneration. This healing response forms adhesions between the flexor tendons in the hand and surrounding tissues, resulting in impaired range of motion and hand function. Mechanistically, inflammation has been strongly linked to adhesion formation, and Prostaglandin E2 (PGE2) is associated with both adhesion formation and tendinopathy. In the present study we tested the hypothesis that deletion of the PGE2 receptor EP4 in S100a4-lineage cells would decrease adhesion formation. S100a4-Cre; EP4 flox/flox (EP4cKOS100a4) repairs healed with improved gliding function at day 14, followed by impaired gliding at day 28, relative to wild type. Interestingly, EP4cKOS100a4 resulted in only transient deletion of EP4, suggesting up-regulation of EP4 in an alternative cell population in these mice. Loss of EP4 in Scleraxis-lineage cells did not alter gliding function, suggesting that Scx-lineage cells are not the predominant EP4 expressing population. In contrast, a dramatic increase in α-SMA+, EP4+ double-positive cells were observed in EP4cKOS100a4 suggesting that EP4cKOS100a4 repairs heal with increased infiltration of EP4 expressing α-SMA myofibroblasts, identifying a potential mechanism of late up-regulation of EP4 and impaired gliding function in EP4cKOS100a4 tendon repairs.
format	article
author	Jessica E. Ackerman Katherine T. Best Regis J. O’Keefe Alayna E. Loiselle
author_facet	Jessica E. Ackerman Katherine T. Best Regis J. O’Keefe Alayna E. Loiselle
author_sort	Jessica E. Ackerman
title	Deletion of EP4 in S100a4-lineage cells reduces scar tissue formation during early but not later stages of tendon healing
title_short	Deletion of EP4 in S100a4-lineage cells reduces scar tissue formation during early but not later stages of tendon healing
title_full	Deletion of EP4 in S100a4-lineage cells reduces scar tissue formation during early but not later stages of tendon healing
title_fullStr	Deletion of EP4 in S100a4-lineage cells reduces scar tissue formation during early but not later stages of tendon healing
title_full_unstemmed	Deletion of EP4 in S100a4-lineage cells reduces scar tissue formation during early but not later stages of tendon healing
title_sort	deletion of ep4 in s100a4-lineage cells reduces scar tissue formation during early but not later stages of tendon healing
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/930aa5bc24584e0e8f7273072e04ab6d
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Deletion of EP4 in S100a4-lineage cells reduces scar tissue formation during early but not later stages of tendon healing

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