Tendons of myostatin-deficient mice are small, brittle, and hypocellular

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Proc Natl Acad Sci U S A. 2007 Dec 27

Tendons of myostatin-deficient mice are small, brittle, and

hypocellular.

Mendias CL, Bakhurin KI, Faulkner JA.

Department of Molecular and Integrative Physiology, University of

Michigan Medical School, Ann Arbor, MI 48109.

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.