Specific inhibition of myostatin activation is beneficial in mouse models of SMA therapy.

Spinal muscular atrophy (SMA) is a neuromuscular disease characterized by loss of α-motor neurons, leading to profound skeletal muscle atrophy. Patients also suffer from decreased bone mineral density and increased fracture risk. The majority of treatments for SMA, approved or in clinic trials, focus on addressing the underlying cause of disease, insufficient production of full-length SMN protein.

Premature expression of a muscle fibrosis axis in chronic HIV infection.

Background: Despite the success of highly active antiretroviral therapy (HAART), HIV infected individuals remain at increased risk for frailty and declines in physical function that are more often observed in older uninfected individuals. This may reflect premature or accelerated muscle aging.

Methods: Skeletal muscle gene expression profiles were evaluated in three uninfected independent microarray datasets including young (19 to 29 years old), middle aged (40 to 45 years old) and older (65 to 85 years old) subjects, and a muscle dataset from HIV infected subjects (36 to 51 years old).

Sca-1 is negatively regulated by TGF-beta1 in myogenic cells.

Sca-1 (stem cell antigen-1) is a member of the Ly-6 family of proteins and regulates cell proliferation, differentiation, and self-renewal in multiple tissues. In skeletal muscle, Sca-1 inhibits both proliferation and differentiation of myogenic cells. Sca-1 expression is dynamically regulated during muscle regeneration, and mice lacking Sca-1 display increased fibrosis following muscle injury.

Sca-1 influences the innate immune response during skeletal muscle regeneration.

Efficient muscle regeneration requires the clearance of dead and dying tissue via phagocytosis before remodeling. We have previously shown that mice lacking stem cell antigen-1 (Sca-1) display a defect in skeletal muscle regeneration characterized by increased fibrosis and decreased turnover of the extracellular matrix. In the present study we demonstrate that Sca-1(-/-) mice have a defect in their capacity to recruit soluble IgM, and subsequently C3 complement, to damaged muscle.

Chemokine expression and control of muscle cell migration during myogenesis.

Adult regenerative myogenesis is vital for restoring normal tissue structure after muscle injury. Muscle regeneration is dependent on progenitor satellite cells, which proliferate in response to injury, and their progeny differentiate and undergo cell-cell fusion to form regenerating myofibers. Myogenic progenitor cells must be precisely regulated and positioned for proper cell fusion to occur.