title: Tendons of myostatin-deficient mice are small, brittle, and hypocellular.
abstract: Tendons play a significant role in the modulation of forces transmitted between bones and skeletal muscles and consequently protect muscle fibers from contraction-induced, or high-strain, injuries. Myostatin (GDF-8) is a negative regulator of muscle mass. Inhibition of myostatin not only increases the mass and maximum isometric force of muscles, but also increases the susceptibility of muscle fibers to contraction-induced injury. We hypothesized that myostatin would regulate the morphology and mechanical properties of tendons. The expression of myostatin and the myostatin receptors ACVR2B and ACVRB was detectable in tendons. Surprisingly, compared with wild type (MSTN(+/+)) mice, the tendons of myostatin-null mice (MSTN(-/-)) were smaller and had a decrease in fibroblast density and a decrease in the expression of type I collagen. Tendons of MSTN(-/-) mice also had a decrease in the expression of two genes that promote tendon fibroblast proliferation: scleraxis and tenomodulin. Treatment of tendon fibroblasts with myostatin activated the p38 MAPK and Smad2/3 signaling cascades, increased cell proliferation, and increased the expression of type I collagen, scleraxis, and tenomodulin. Compared with the tendons of MSTN(+/+) mice, the mechanical properties of tibialis anterior tendons from MSTN(-/-) mice had a greater peak stress, a lower peak strain, and increased stiffness. We conclude that, in addition to the regulation of muscle mass and force, myostatin regulates the structure and function of tendon tissues.
authors.affiliation: Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Mendias
authors.forename: Konstantin I
authors.initials: KI
authors.lastname: Bakhurin
authors.forename: John A
authors.initials: JA
authors.lastname: Faulkner
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D005347:Fibroblasts; D005786:Gene Expression Regulation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008954:Models, Biological; D008957:Models, Genetic; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism; D009132:Muscles / Q000473:pathology; D055435:Myostatin; D013710:Tendons / Q000002:abnormalities* / Q000473:pathology*; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000502:physiology*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D055435:Myostatin; D016212:Transforming Growth Factor beta; C525912:Mstn protein, mouse; C503815:Scx protein, mouse