Bigger Muscles and Smaller Tendons ‐ 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 (MSTN) 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. Due to the protective role of tendons in preventing contraction‐induced injury, and the greater susceptibility of muscles from MSTN−/− mice 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, were detectable in tendons. Surprisingly, compared with MSTN+/+ mice, the tendons of myostatin‐deficient mice MSTN−/− were smaller, 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, lower peak strain and a increased stiffness. We conclude that in addition to the regulation of muscle mass and force, myostatin regulates the structure and function of tendon tissues.