Gaut, L. | Search bioRxiv

bioRxiv2024

Human adipose stromal cells differentiate towards a tendon phenotype with extracellular matrix production and adapted visco-elastic properties in a 3D-culture system

Tendon cell differentiation relies on molecular and mechanical parameters that control the expression of tendon-associated transcription factors and extracellular matrix proteins. However, the minimal cues able to initiate tendon differentiation from progenitor cells remains unknown. We analysed the tendon differentiation program in human adipose stromal cells (hASCs) cultured in a minimal 3D-system. We generated 3D-hASC constructs by embedding hASCs in a type-I collagen gel under a static uniaxial geometrical constraint with no additional molecular and mechanical cues, and assessed tendon-associated gene expression and mechanical properties for up to three weeks in culture. Analysis of tendon-associated genes revealed a molecular progression consistent with the acquisition of a tendon phenotype. The analysis of viscoelastic properties of 3D-hASC constructs by nano-indentation indicated a progressive increase in tissue stiffness up to 10 kPa, concomitant with a reduced stress relaxation indicative of solid-like mechanical properties. These changes in mechanical properties parallel the molecular change of matrix genes during the time of cultures. In summary, we have established that hASCs cultured in a minimal 3D-system progress into the tendon differentiation program associated with variations of mechanical properties.

developmental biology↗

bioRxiv2024

Different outcomes of endurance and resistance exercise in skeletal muscles of Oculopharyngeal muscular dystrophy.

BackgroundExercise is widely considered to have beneficial impact on skeletal muscle aging. In addition, there are also several studies demonstrating a positive effect of exercise on muscular dystrophies. Oculopharyngeal muscular dystrophy (OPMD) is a late-onset autosomal dominant inherited neuromuscular disorder caused by mutations in the PAPBN1 gene. These mutations consist in short (1-8) and meiotically stable GCN trinucleotide repeat expansions in its coding region responsible for the formation of PAPBN1 intranuclear aggregates. This study aims to characterize the effects of two types of chronic exercise, resistance and endurance, on the OPMD skeletal muscle phenotype using a relevant murine model of OPMD. MethodsIn this study, we tested two protocols of exercise. In the first, based on endurance exercise, FvB (wild-type) and A17 (OPMD) mice underwent a 6-week-long motorized treadmill protocol consisting in 3 sessions per week of running 20cm/s for 20 minutes. In the second protocol, based on resistance exercise generated by chronic mechanical overload (OVL), surgical removal of gastrocnemius and soleus muscles was performed, inducing hypertrophy of the plantaris muscle. In both types of exercise, muscles of A17 and FvB mice were compared to those of respective sedentary mice. For all the groups, force measurement, muscle histology and molecular analyses were conducted. ResultsFollowing the endurance exercise protocol, we did not observe any major changes in the muscle physiological parameters, but an increase in the number of PABPN1 intranuclear aggregates and enhanced collagen deposition in the exercised A17 OPMD mice. In the resistance overload protocol, we also observed an increased collagen deposition in the A17 OPMD mice which was associated with larger muscle mass and fiber cross sectional area and increased absolute maximal force as well as a reduction in PABPN1 aggregate number. ConclusionsRunning exercise and mechanical overload led to very different outcome in skeletal muscles of A17 mice. Both types of exercise enhanced collagen deposition but while the running protocol increased aggregates, the OVL reduced them. More importantly OVL reversed muscle atrophy and maximal force in the A17 mice. Our study performed in a relevant model gives an indication of the effect of different types of exercise on OPMD muscle which should be further evaluated in humans for future recommendations as a part of the lifestyle of individuals with OPMD.

pathology↗