GDF-8

Description

Myostatin (GDF-8), a member of the TGF-beta superfamily of growth and differentiation factors, is most well-known as a potent suppressor of muscle growth, development, and regeneration. It is highly expressed in skeletal muscle, and myostatin loss-of-function leads to doubling skeletal muscle mass. Mice lacking myostatin show a significant increase in muscle mass, and congenital absence of myostatin is associated with increased muscle mass in humans and dogs. It has also been shown that factors which inhibit myostatin, such as follistatin, can improve muscle regeneration and decrease fibrosis in injured muscles[1].

Uses

Myostatin (GDF-8) is a secreted protein that is a potent inhibitor of muscle growth and development, whereas GDF-8 is also expressed early in the fracture healing process. Thus, blocking GDF-8 signalling in the injured limb improves fracture healing and promotes muscle regeneration. These data suggest that GDF-8 inhibitors may be effective in improving wound repair in orthopaedic trauma and extremity injuries.

Biological Activity

GDF-8 is expressed in both developing and adult skeletal muscle. It controls myoblast proliferation and is a potent negative regulator of skeletal muscle mass. It is up-regulated in mechanically stressed cardiomyocytes and induces skeletal muscle atrophy commonly seen in heart failure.The prepeptide of GDF-8 is cleaved from GDF-8 but remains associated with mature GDF-8 and exerts an inhibitory effect.The activity of GDF-8 is also inhibited by binding to Follistatin, FLRG, Decorin or GASP-1. Active GDF-8 signals through a receptor complex containing activin RIIB and activin RIB/ALK-4 or TGF-beta RI/ALK-5.

References

[1] Mark W Hamrick. “Recombinant myostatin (GDF-8) propeptide enhances the repair and regeneration of both muscle and bone in a model of deep penetrant musculoskeletal injury.” Journal of Trauma-Injury Infection and Critical Care 69 3 (2010): 579–83.