1. Reduction of Tendon Fibrosis Using Galectin-3 Inhibitors.
- Author
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Spielman AF, Griffin MF, Titan AL, Guardino N, Cotterell AC, Akras D, Wan DC, and Longaker MT
- Subjects
- Animals, Mice, Collagen Type I metabolism, Collagen Type I genetics, Male, Random Allocation, Fibrosis, Galectin 3 antagonists & inhibitors, Galectin 3 metabolism, Mice, Inbred C57BL, Disease Models, Animal, Achilles Tendon injuries, Achilles Tendon pathology, Achilles Tendon drug effects, Tendon Injuries drug therapy, Tendon Injuries pathology
- Abstract
Background: Fibrosis is a complication of both tendon injuries and repairs. The authors aimed to develop a mouse model to assess tendon fibrosis and to identify an antifibrotic agent capable of overcoming it., Methods: The Achilles tendon of adult C57Bl/6 mice was exposed via skin incision, followed by 50% tendon injury and abrasion with sandpaper. Sham operations were conducted on contralateral hindlimbs. Histologic analyses and immunofluorescent staining for fibrotic markers (collagen type 1 [ Col1 ], α-smooth muscle actin [ α-SMA ]) were used to confirm that the model induced tendon fibrosis. A second experiment further examined the role of α-SMA in adhesion formation using α-SMA.mTmG mice (6 to 8 weeks old; n = 3) with the same injury model. Lastly, α-SMA.mTmG mice were randomized to either condition 1 (tendon injury [control group]) or condition 2 (tendon injury with galectin-3 inhibitor [Gal3i] treatment at time of injury [treatment group])., Results: Histologic analyses confirmed tendon thickening and collagen deposition after tendon injury and abrasion compared with control. Immunofluorescence showed higher levels of Col1 and α-SMA protein expression after injury compared with sham ( P < 0.05). Real-time quantitative polymerase chain reaction also demonstrated increased gene expression of Col1 and α-SMA after injury compared with sham ( P < 0.05). Gal3 protein expression also increased after injury and colocalized with α-SMA+ fibroblasts surrounding the fibrotic tendon. Gal3i treatment decreased collagen deposition and scarring observed in the treatment group ( P < 0.05)., Conclusions: The authors' study provides a reproducible and reliable model to investigate tendon fibrosis. Findings suggest the potential of Gal3i to overcome fibrosis resulting from tendon injuries., Clinical Relevance Statement: Tendon injuries are common presentations to hand surgeons. Complications include adhesion formation, which results in reduced strength and frequent reinjury. Advancements in management require a better understanding of the mechanisms behind tendon fibrosis in order to identify ways to overcome it., (Copyright © 2023 by the American Society of Plastic Surgeons.)
- Published
- 2024
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