IBMS BoneKEy | Perspective

Myostatin (GDF-8) as a therapeutic target for the prevention of osteoporotic fractures

Mark W Hamrick



DOI:10.1138/20100423

Abstract

It is widely recognized that myostatin (GDF-8), a member of the transforming growth factor beta (TGFβ) superfamily of growth and differentiation factors, suppresses muscle growth and development. Increased myostatin expression can induce muscle wasting and muscle atrophy, whereas myostatin deficiency leads to a marked increase in muscle mass. Myostatin deficiency also appears to improve bone density and bone regeneration. Hence, myostatin inhibitors may not only improve muscle mass and reduce fall risk but might also increase bone strength. Recent studies have shown that myostatin exerts its effects by binding the type IIB activin receptor (ActRIIB, or Acvr2b), activating a TGFβ signaling pathway, and inhibiting Wnt signaling. Myostatin function can be inhibited by a recombinant myostatin propeptide, myostatin antibody, or soluble decoy type IIB activin receptor. Recent studies demonstrate that these myostatin inhibitors are effective at increasing both muscle mass and bone formation in vivo. These new findings reveal that molecules targeting myostatin signaling may be novel, effective therapeutic agents for improving muscle strength, increasing bone mass, and preventing falls and bone fractures.


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