Skeletal myofibers are injured due to mechanical stresses experienced during physical activity, or due to myofiber fragility caused by genetic diseases. The injured myofiber needs to be repaired or regenerated to restore the loss in muscle tissue function. Myofiber repair and regeneration requires coordinated action of various intercellular signaling factors—including proteins, inflammatory cytokines, miRNAs, and membrane lipids. It is increasingly being recognized release and transmission of these signaling factors involves extracellular vesicle (EV) released by myofibers and other cells in the injured muscle. Intercellular signaling by these EVs alters the phenotype of their target cells either by directly delivering the functional proteins and lipids or by modifying longer-term gene expression. These changes in the target cells activate downstream pathways involved in tissue homeostasis and repair. The EVs are heterogeneous with regards to their size, composition, cargo, location, as well as time-course of genesis and release. These differences impact on the subsequent repair and regeneration of injured skeletal muscles. This review focuses on how intracellular vesicle production, cargo packaging, and secretion by injured muscle, modulates specific reparative, and regenerative processes. Insights into the formation of these vesicles and their signaling properties offer new understandings of the orchestrated response necessary for optimal muscle repair and regeneration.

Muscle cell plasma membrane is frequently damaged by mechanical activity, and its repair requires the membrane protein dysferlin. We previously identified that, similar to dysferlin deficit, lack of annexin A2 (AnxA2) also impairs repair of skeletal myofibers. Here, we have studied the mechanism of AnxA2-mediated muscle cell membrane repair in cultured muscle cells. We find that injury-triggered increase in cytosolic calcium causes AnxA2 to bind dysferlin and accumulate on dysferlin-containing vesicles as well as with dysferlin at the site of membrane injury. AnxA2 accumulates on the injured plasma membrane in cholesterol-rich lipid microdomains and requires Src kinase activity and the presence of cholesterol. Lack of AnxA2 and its failure to translocate to the plasma membrane, both prevent calcium-triggered dysferlin translocation to the plasma membrane and compromise repair of the injured plasma membrane. Our studies identify that Anx2 senses calcium increase and injury-triggered change in plasma membrane cholesterol to facilitate dysferlin delivery and repair of the injured plasma membrane.

Aims To determine leg intermuscular (IMAT) and subcutaneous (SQAT) adipose tissue and their relationships with muscle performance and function in obese adults with and without type 2 diabetes and peripheral neuropathy (T2DMPN). Methods Seventy-nine age-matched obese adults were studied, 13 T2DM, 54 T2DMPN, and 24 obese controls. Leg fat (%IMAT, %SQAT) volumes were quantified using MRI. Ankle plantar flexion (PF) torque and power were assessed with isokinetic dynamometry. Physical function was assessed with 9-item Physical Performance Test (PPT), 6-minute walk distance, single-limb balance, and time to ascend 10 stairs. One-way ANOVAs determined group differences, and multiple regression predicted PPT score from disease status, % IMAT, and PF power. Results T2DMPN participants had 37% greater IMAT volumes and 15% lower SQAT volumes than controls (p=. 01). T2DMPN and T2DM showed reduced PF torque and power compared to controls. T2DMPN participants had lower PPT score, 6′ walk, single-limb balance, and stair climbing than controls (all p<.05) . %IMAT volume correlated inversely, and %SQAT correlated directly, with PPT. Leg %IMAT and disease status predicted 49% of PPT score. Conclusions T2DMPN may represent a shift in adipose tissue accumulation from SQAT to IMAT depots, which is inversely associated with muscle performance and physical function.

Deficits in plasma membrane repair have been identified in dysferlinopathy and Duchenne Muscular Dystrophy, and contribute to progressive myopathy. Although Facioscapulohumeral Muscular Dystrophy (FSHD) shares clinicopathological features with these muscular dystrophies, it is unknown if FSHD is characterized by plasma membrane repair deficits. Therefore, we exposed immortalized human FSHD myoblasts, immortalized myoblasts from unaffected siblings, and myofibers from a murine model of FSHD (FLExDUX4) to focal, pulsed laser ablation of the sarcolemma. Repair kinetics and success were determined from the accumulation of intracellular FM1-43 dye post-injury. We subsequently treated FSHD myoblasts with a DUX4-targeting antisense oligonucleotide (AON) to reduce DUX4 expression, and with the antioxidant Trolox to determine the role of DUX4 expression and oxidative stress in membrane repair. Compared to unaffected myoblasts, FSHD myoblasts demonstrate poor repair and a greater percentage of cells that failed to repair, which was mitigated by AON and Trolox treatments. Similar repair deficits were identified in FLExDUX4 myofibers. This is the first study to identify plasma membrane repair deficits in myoblasts from individuals with FSHD, and in myofibers from a murine model of FSHD. Our results suggest that DUX4 expression and oxidative stress may be important targets for future membrane-repair therapies.

"Accuracy and precision of an accelerometer-based smartphone app designed to monitor and record angular movement over time. " Telemedicine and e-Health.22,4. 302-309. (2016 AbstractBackground: Therapeutic exercise is a central component in the management of many common conditions. It is imperative, therefore, that clinicians monitor and correct patient performance to facilitate the use of proper form both in the clinic and during home exercise programs. Although clinicians are trained to prescribe exercise and analyze form, there are many subtleties that may be missed by relying on visual assessment. This study investigated the accuracy and precision of a novel, exercise-training smartphone application (app), running on an iPhone Ò (Apple, Cupertino, CA) 4