Tendons of myostatin-deficient mice are small, brittle, and hypocellular
- 8 January 2008
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 105 (1) , 388-393
- https://doi.org/10.1073/pnas.0707069105
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.Keywords
This publication has 55 references indexed in Scilit:
- Generation of transgenic tendon reporters, ScxGFP and ScxAP, using regulatory elements of the scleraxis geneDevelopmental Dynamics, 2007
- Myostatin Induces Cyclin D1 Degradation to Cause Cell Cycle Arrest through a Phosphatidylinositol 3-Kinase/AKT/GSK-3β Pathway and Is Antagonized by Insulin-like Growth Factor 1Journal of Biological Chemistry, 2007
- Contractile properties of EDL and soleus muscles of myostatin-deficient miceJournal of Applied Physiology, 2006
- Extracellular matrix adaptation of tendon and skeletal muscle to exerciseJournal of Anatomy, 2006
- Regulation of GDF-8 signaling by the p38 MAPKCellular Signalling, 2004
- Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT MethodMethods, 2001
- SB 203580 is a specific inhibitor of a MAP kinase homologue which is stimulated by cellular stresses and interleukin‐1Published by Wiley ,2000
- Growth stimulation of murine fibroblasts by TGF-β1 depends on the expression of a functional p53 proteinOncogene, 1999
- Sclerotome-related helix-loop-helix type transcription factor (scleraxis) mRNA is expressed in osteoblasts and its level is enhanced by type-β transforming growth factorJournal of Endocrinology, 1996
- A clinical reviewMuscle & Nerve, 1978