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

2017 ◽  
Author(s):  
Jessica E. Ackerman ◽  
Katherine T. Best ◽  
Regis J. O’Keefe ◽  
Alayna E. Loiselle

AbstractTendon 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; EP4flox/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.

2020 ◽  
Author(s):  
Katherine T. Best ◽  
Emma Knapp ◽  
Constantinos Ketonis ◽  
Jennifer H. Jonason ◽  
Hani A. Awad ◽  
...  

AbstractAcute tendon injuries are characterized by excessive matrix deposition that impedes regeneration and disrupts functional improvements. Inflammation is postulated to drive pathologic scar tissue formation, with nuclear factor kappa B (NF-κB) signaling emerging as a candidate pathway in this process. However, characterization of the spatial and temporal activation of canonical NF-κB signaling during tendon healing in vivo, including identification of the cell populations activating NF-κB, is currently unexplored. Therefore, we aimed to determine which cell populations activate canonical NF-κB signaling following flexor tendon repair with the goal of delineating cell-specific functions of NF-κB signaling during scar mediated tendon healing. Immunofluorescence revealed that both tendon cells and myofibroblasts exhibit prolonged activation of canonical NF-κB signaling into the remodeling phase of healing. Using cre-mediated knockout of the canonical NF-κB kinase (IKKβ), we discovered that suppression of canonical NF-κB signaling in Scleraxis-lineage cells increased myofibroblast content and scar tissue formation. Interestingly, Scleraxis-lineage specific knockout of IKKβ increased the incidence of apoptosis, suggesting that canonical NF-κB signaling may be mediating cell survival during tendon healing. These findings suggest indispensable roles for canonical NF-κB signaling during flexor tendon healing.One Sentence SummaryScleraxis-lineage specific knockdown of persistent canonical IKKβ/NF-κB drives scar formation and apoptotic signaling during flexor tendon healing.


2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Jessica E. Ackerman ◽  
Katherine T. Best ◽  
Regis J. O’Keefe ◽  
Alayna E. Loiselle

2021 ◽  
Vol 10 (8) ◽  
pp. 1613
Author(s):  
Alessandro Crosio ◽  
Giulia Ronchi ◽  
Benedetta Elena Fornasari ◽  
Simonetta Odella ◽  
Stefania Raimondo ◽  
...  

As a consequence of trauma or surgical interventions on peripheral nerves, scar tissue can form, interfering with the capacity of the nerve to regenerate properly. Scar tissue may also lead to traction neuropathies, with functional dysfunction and pain for the patient. The search for effective antiadhesion products to prevent scar tissue formation has, therefore, become an important clinical challenge. In this review, we perform extensive research on the PubMed database, retrieving experimental papers on the prevention of peripheral nerve scarring. Different parameters have been considered and discussed, including the animal and nerve models used and the experimental methods employed to simulate and evaluate scar formation. An overview of the different types of antiadhesion devices and strategies investigated in experimental models is also provided. To successfully evaluate the efficacy of new antiscarring agents, it is necessary to have reliable animal models mimicking the complications of peripheral nerve scarring and also standard and quantitative parameters to evaluate perineural scars. So far, there are no standardized methods used in experimental research, and it is, therefore, difficult to compare the results of the different antiadhesion devices.


2018 ◽  
Vol 7 (8) ◽  
pp. 283-297 ◽  
Author(s):  
Lyn M. Wise ◽  
Gabriella S. Stuart ◽  
Nicola C. Real ◽  
Stephen B. Fleming ◽  
Andrew A. Mercer

2005 ◽  
Vol 26 (1) ◽  
pp. 45-50 ◽  
Author(s):  
Hakan Cincik ◽  
Atila Gungor ◽  
Adem Cakmak ◽  
Atilla Omeroglu ◽  
Ethem Poyrazoglu ◽  
...  

2020 ◽  
Vol 11 (10) ◽  
pp. 447-451
Author(s):  
Amanda Curtis

Heavily contaminated wounds are a common occurrence in both referral and primary care practice, with traumatic and bite wounds being among the most typical aetiologies seen. Each type of wound can be affected by numerous factors that can inhibit the healing process, one of these major factors is infection. Wound infections and the formation of biofilms can present veterinary nurses with a variety of challenges, which is why it is important that we understand the difference between normal inflammatory signs and the signs of infection. The early identification of infection and biofilms within a wound can influence healing times, scar tissue formation and length of healing. This article aims to highlight the difference between inflammation and infection, the different levels of contamination within a wound, and ways to decipher between superficial and deep tissue infections.


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