Bone architecture and disc degeneration in the lumbar spine of mice lacking GDF-8 (myostatin)

GDF-8, also known as myostatin, is a member of the transforming growth factor-β superfamily of secreted growth and differentiation factors that is expressed in vertebrate skeletal muscle. Myostatin functions as a negative regulator of skeletal muscle growth and myostatin null mice show a doubling of muscle mass compared to normal mice. We describe here morphology of the lumbar spine in myostatin knockout (Mstn^-/-) mice using histological and densitometric techniques. The Mstn^-/- mice examined in this study weigh approximately 10% more than controls (p < 0.001) but the iliopsoas muscle is over 50% larger in the knockout mice than in wild-type mice (p < 0.001). Peripheral quantitative computed tomography (pQCT) data from the fifth lumbar vertebra show that mice lacking myostatin have approximately 50% greater trabecular bone mineral density (p = 0.001) and significantly greater cortical bone mineral content than normal mice. Toluidine blue staining of the intervertebral disc between L4-L5 reveals loss of proteoglycan staining in the hyaline end plates and inner annulus fibrosus of the knockout mice. Loss of cartilage staining in the caudal end plate of L4 is due to ossification of the end plate in the myostatin-deficient animals. Results from this study suggest that increased muscle mass in mice lacking myostatin is associated with increased bone mass as well as degenerative changes in the intervertebral disc.