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

Scientific Reports
Jessica E AckermanAlayna E Loiselle

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...Continue Reading

References

Oct 1, 1985·Pathology, Research and Practice·M KvistH Kvist
Apr 1, 1997·Scandinavian Journal of Medicine & Science in Sports·M JärvinenW Leadbetter
Oct 5, 2002·Hand Surgery : an International Journal Devoted to Hand and Upper Limb Surgery and Related Research : Journal of the Asia-Pacific Federation of Societies for Surgery of the Hand·Sheri B Feldscher, Lawrence H Schneider
Jan 9, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Etsushi Kuroda, Uki Yamashita
Dec 3, 2003·Annals of Biomedical Engineering·Pedro K BeredjiklianLouis J Soslowsky
Feb 24, 2004·The American Journal of Sports Medicine·Zhaozhu LiJames H C Wang
Jun 10, 2004·Clinical Orthopaedics and Related Research·James H-C WangMustafa Khan
Oct 21, 2004·The American Journal of Sports Medicine·Olena VirchenkoPer Aspenberg
Dec 25, 2004·American Journal of Respiratory and Critical Care Medicine·William E LawsonTimothy S Blackwell
Jan 18, 2005·Clinical Journal of Sport Medicine : Official Journal of the Canadian Academy of Sport Medicine·Mustafa H KhanJames H-C Wang
Apr 22, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Bethany B MooreMarc Peters-Golden
Aug 18, 2005·Kidney International·Yoshiharu NishitaniEric G Neilson
Oct 27, 2005·Investigative Ophthalmology & Visual Science·Motonobu UenoLeonard D Shultz
Sep 1, 2006·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·Michele FavataLouis J Soslowsky
Sep 28, 2006·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·Hiroshi KoshimaNaoki Ishiguro
Oct 6, 2007·American Journal of Respiratory and Critical Care Medicine·Steven K HuangMarc Peters-Golden
Jan 11, 2008·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·Sys HasslundHani A Awad
Dec 4, 2008·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·Alayna E LoiselleRegis J O'Keefe
Aug 19, 2009·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·Jianying Zhang, James H-C Wang
Dec 10, 2009·Journal of Tissue Viability·Bin Li, James H-C Wang
Nov 23, 2010·Arteriosclerosis, Thrombosis, and Vascular Biology·Eva H C TangPeter Libby
Dec 22, 2010·Proceedings of the National Academy of Sciences of the United States of America·Christoph H ÖsterreicherDavid A Brenner
May 10, 2012·PloS One·Utako YokoyamaYoshihiro Ishikawa
Dec 18, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Kirsty F MacKenzieJ Simon C Arthur
Aug 12, 2014·Journal of Hepatology·Lin ChenZhihai Qin
Feb 14, 2015·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·Leesa M GalatzScott A Rodeo
May 20, 2015·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·Andrea L LalleyJason T Shearn
Dec 9, 2015·Proceedings of the National Academy of Sciences of the United States of America·Bing LuanMarc Montminy
Dec 25, 2015·Proceedings. Biological Sciences·A Katharina SimonAndrew McMichael
Jan 24, 2016·Biochimica Et Biophysica Acta·Susanne Sattler, Nadia Rosenthal
Sep 30, 2016·Journal of Visualized Experiments : JoVE·Nathaniel A DymentDavid W Rowe
Sep 30, 2016·Journal of Visualized Experiments : JoVE·Jessica E Ackerman, Alayna E Loiselle

❮ Previous
Next ❯

Citations

Apr 6, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Katherine T Best, Alayna E Loiselle
Jun 25, 2019·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·Jessica E AckermanAlayna E Loiselle
Jul 10, 2019·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·Andrey ZuskovLouis J Soslowsky
Dec 16, 2019·British Medical Bulletin·Emanuele ChisariNicola Maffulli
Mar 13, 2020·British Medical Bulletin·Emanuele ChisariNicola Maffulli
Jun 3, 2020·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·Katherine T BestAlayna E Loiselle
May 28, 2019·ELife·Jessica E AckermanAlayna E Loiselle
Feb 16, 2021·Current Tissue Microenvironment Reports·Connor C LeekMegan L Killian
Apr 30, 2021·Development·Lauren BobzinAmy E Merrill

❮ Previous
Next ❯

Methods Mentioned

BETA
PCR

Software Mentioned

Visiopharm

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.