Multifaceted Roles of Heparan Sulfate Proteoglycans in Skeletal Muscle: Bridging Physiological Muscle Function Control to Therapeutic Strategies for Muscle Diseases

Heparan sulfate proteoglycans (HSPGs) are extracellular matrix components that play central roles in skeletal muscle development, maintenance, and regeneration. HSPGs are localized to the basement membrane, sarcolemma, neuromuscular junction, and satellite cell niche, where they exert multifaceted functions, including providing structural stability, storing and releasing growth factors, and controlling mechanotransduction. Throughout each stage from muscle development to maturation, the expression levels of HSPGs and modification patterns of HS chains change dynamically, precisely controlling myogenesis. Changes in HS sulfation patterns regulate growth factor signaling and affect muscle cell proliferation and differentiation. Based on mechanotransduction control mechanisms elucidated through our perlecan research, this review demonstrates that mechanotransduction control by HSPGs constitutes an important molecular basis for muscle mass and metabolic regulation. HSPG abnormalities are associated with muscular dystrophy, sarcopenia, and metabolic diseases, making the development of therapeutic strategies targeting HSPGs and HS chains a promising area of research.