Glossary
Myostatin (GDF-8)
Myostatin, a growth factor of the TGF-beta family, restrains skeletal muscle mass via ActRIIB and SMAD2/3. Its processing, latency and research background.
Myostatin — also known as growth differentiation factor 8, or GDF-8 — is a TGF-beta superfamily ligand that skeletal muscle secretes in the largest amounts. Furin processes its precursor into two parts — the propeptide and a mature dimer held together by a disulfide bond. In the circulation the dimer stays inactive, bound to its propeptide, until proteases of the BMP-1/tolloid group liberate it.
Its role as a brake on muscle
The freed dimer docks onto ActRIIB (the activin type IIB receptor), recruits ALK4 or ALK5, and SMAD2/3 become phosphorylated as a result; this suppresses muscle differentiation programmes and cross-talks with Akt/mTOR signalling. Evidence that it acts as a negative regulator comes from animals and people lacking it: a knockout mouse described in 1997, the double-muscled Belgian Blue and Piedmontese cattle breeds, whippets carrying the mutation, and a single human case published in 2004.
This biology made blocking myostatin an obvious therapeutic hypothesis, and a series of programmes — antibodies, soluble receptor decoys and follistatin-based approaches — went on into human trials. The outcomes have pointed consistently one way: rises in lean mass were reported, improvements in function and strength mostly were not, and a number of programmes were stopped. Our research-grade GDF-8 propeptide and associated reagents are intended exclusively for in vitro and preclinical laboratory use.
Related terms and material
IGF-1 · recombinant · preclinical. Reference material: GDF-8 / myostatin propeptide, ACE-031, IGF & muscle peptides. Further reading: peptides for muscle growth research.