Role of fibro-adipogenic progenitor cells in muscle atrophy and musculoskeletal diseases

Maintaining muscle mass is clinically important as muscle helps to regulate metabolic systems of the body as well as support activities of daily living that require mobility, strength, and power. Losing muscle mass decreases an individual's independence and quality of life, and at the same time increases the risk of disease burden. Fibro-adipogenic progenitor (FAP) cells are a group of muscle progenitor cells that play an important role in muscle regeneration and maintenance of skeletal muscle fiber size. These important functions of FAPs are mediated by a complex secretome that interacts in a paracrine manner to stimulate muscle satellite cells to divide and differentiate. Dysregulation of FAP differentiation leads to fibrosis, fatty infiltration, muscle atrophy, and impaired muscle regeneration. Functional deficits in skeletal muscle resulting from atrophy, fibrosis, or fatty infiltration will reduce biomechanical stresses on the skeleton, and both FAP-derived adipocytes and FAPs themselves are likely to secrete factors that can induce bone loss. These findings suggest that FAPs represent a cell population to be targeted therapeutically to improve both muscle and bone health in settings of aging, injury, and disease.