ArticlePloS one2015
Systemic EP4 Inhibition Increases Adhesion Formation in a Murine Model of Flexor Tendon Repair.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
13 citing papers in PubMed, 23 citations in OpenAlex.
- Peritendinous adhesion: Therapeutic targets and progress of drug therapy.Computational and structural biotechnology journal · 2024Review
- Advancing Novel Strategies against Post-surgical Tendon Adhesion Bands, Exploring New Frontiers.Current pharmaceutical design · 2024Review
- The effects of NF-κB suppression on the early healing response following intrasynovial tendon repair in a canine model.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2023Article
- Neutralization of excessive levels of active TGF-β1 reduces MSC recruitment and differentiation to mitigate peritendinous adhesion.Bone research · 2023Article
- A Simplified Murine Model to Imitate Flexor Tendon Adhesion Formation without Suture.Biomimetics (Basel, Switzerland) · 2022Article
- Role of prostaglandin E2 in tissue repair and regeneration.Theranostics · 2021Review
- Thermal pretreatment promotes the protective effect of HSP70 against tendon adhesion in tendon healing by increasing HSP70 expression.Molecular medicine reports · 2019Article
- Effect of aging on the tendon structure and tendon-associated gene expression in mouse foot flexor tendon.Biomedical reports · 2019Article
- Tenomodulin is essential for prevention of adipocyte accumulation and fibrovascular scar formation during early tendon healing.Cell death & disease · 2017Article
- Deletion of EP4 in S100a4-lineage cells reduces scar tissue formation during early but not later stages of tendon healing.Scientific reports · 2017Article
- Obesity/Type II diabetes alters macrophage polarization resulting in a fibrotic tendon healing response.PloS one · 2017Article
- Murine Flexor Tendon Injury and Repair Surgery.Journal of visualized experiments : JoVE · 2016Article
- Structural and Ultrastructural Characteristics of Bone-Tendon Junction of the Calcaneal Tendon of Adult and Elderly Wistar Rats.PloS one · 2016Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Flexor tendon injuries are a common clinical problem, and repairs are frequently complicated by post-operative adhesions forming between the tendon and surrounding soft tissue. Prostaglandin E2 and the EP4 receptor have been implicated in this process following tendon injury; thus, we hypothesized that inhibiting EP4 after tendon injury would attenuate adhesion formation. A model of flexor tendon laceration and repair was utilized in C57BL/6J female mice to evaluate the effects of EP4 inhibition on adhesion formation and matrix deposition during flexor tendon repair. Systemic EP4 antagonist or vehicle control was given by intraperitoneal injection during the late proliferative phase of healing, and outcomes were analyzed for range of motion, biomechanics, histology, and genetic changes. Repairs treated with an EP4 antagonist demonstrated significant decreases in range of motion with increased resistance to gliding within the first three weeks after injury, suggesting greater adhesion formation. Histologic analysis of the repair site revealed a more robust granulation zone in the EP4 antagonist treated repairs, with early polarization for type III collagen by picrosirius red staining, findings consistent with functional outcomes. RT-PCR analysis demonstrated accelerated peaks in F4/80 and type III collagen (Col3a1) expression in the antagonist group, along with decreases in type I collagen (Col1a1). Mmp9 expression was significantly increased after discontinuing the antagonist, consistent with its role in mediating adhesion formation. Mmp2, which contributes to repair site remodeling, increases steadily between 10 and 28 days post-repair in the EP4 antagonist group, consistent with the increased matrix and granulation zones requiring remodeling in these repairs. These findings suggest that systemic EP4 antagonism leads to increased adhesion formation and matrix deposition during flexor tendon healing. Counter to our hypothesis that EP4 antagonism would improve the healing phenotype, these results highlight the complex role of EP4 signaling during tendon repair.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.