Fibro-adipogenic progenitors prevent skeletal muscle degeneration at acute phase upon tendon rupture in a murine tibialis anterior tenotomy model.

Abstract

Background: Fibro-adipogenic progenitors (FAPs) are a group of mesenchymal stem cells that cause fibro-fatty degeneration in skeletal muscle in various chronic disease models. FAPs also play a role in preventing muscle degeneration at acute stages during disease progression. However, few studies have reported the changes in and function of FAPs in the acute phase after tendon rupture.

Aim: To clarify the changes in the number of FAPs and their impact on skeletal muscle soon after tendon rupture to facilitate future studies targeting FAPs to treat muscle degeneration.

Methods: We utilized Pdgfra-H2B::eGFP mice to trace and quantify FAPs in a tibialis anterior tenotomy (TAT) model at 0 and 3 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, and 6 weeks post-injury, and the results were further validated using fluorescence-activated cell sorting analysis with C57BL/6 mice at the same post-injury timepoints. We subsequently used PdgfraCre^ERT::Rosa^DTA mice, and evaluated the severity of post-TAT skeletal muscle degeneration with or without FAP-depletion.

Results: The number of FAPs peaked at 1 week post-TAT before gradually declining to a level comparable to that pre-TAT. The change in the number of FAPs was potentially temporally correlated with the progression of skeletal muscle degeneration after TAT. FAP-depletion led to more severe degeneration early after TAT, indicating that FAPs potentially alleviate muscle degeneration after tendon rupture in the early post-injury phase.

Conclusion: FAPs potentially alleviate the degeneration of skeletal muscle in the acute stage after tendon rupture.