Role of Extracellular Matrix in Adaptation of Tendon and Skeletal Muscle to Mechanical Loading

2004 ◽  
Vol 84 (2) ◽  
pp. 649-698 ◽  
Author(s):  
MICHAEL KJÆR

Kjær, Michael. Role of Extracellular Matrix in Adaptation of Tendon and Skeletal Muscle to Mechanical Loading. Physiol Rev 84: 649–698, 2004; 10.1152/physrev.00031.2003.—The extracellular matrix (ECM), and especially the connective tissue with its collagen, links tissues of the body together and plays an important role in the force transmission and tissue structure maintenance especially in tendons, ligaments, bone, and muscle. The ECM turnover is influenced by physical activity, and both collagen synthesis and degrading metalloprotease enzymes increase with mechanical loading. Both transcription and posttranslational modifications, as well as local and systemic release of growth factors, are enhanced following exercise. For tendons, metabolic activity, circulatory responses, and collagen turnover are demonstrated to be more pronounced in humans than hitherto thought. Conversely, inactivity markedly decreases collagen turnover in both tendon and muscle. Chronic loading in the form of physical training leads both to increased collagen turnover as well as, dependent on the type of collagen in question, some degree of net collagen synthesis. These changes will modify the mechanical properties and the viscoelastic characteristics of the tissue, decrease its stress, and likely make it more load resistant. Cross-linking in connective tissue involves an intimate, enzymatical interplay between collagen synthesis and ECM proteoglycan components during growth and maturation and influences the collagen-derived functional properties of the tissue. With aging, glycation contributes to additional cross-linking which modifies tissue stiffness. Physiological signaling pathways from mechanical loading to changes in ECM most likely involve feedback signaling that results in rapid alterations in the mechanical properties of the ECM. In developing skeletal muscle, an important interplay between muscle cells and the ECM is present, and some evidence from adult human muscle suggests common signaling pathways to stimulate contractile and ECM components. Unaccostumed overloading responses suggest an important role of ECM in the adaptation of myofibrillar structures in adult muscle. Development of overuse injury in tendons involve morphological and biochemical changes including altered collagen typing and fibril size, hypervascularization zones, accumulation of nociceptive substances, and impaired collagen degradation activity. Counteracting these phenomena requires adjusted loading rather than absence of loading in the form of immobilization. Full understanding of these physiological processes will provide the physiological basis for understanding of tissue overloading and injury seen in both tendons and muscle with repetitive work and leisure time physical activity.

1994 ◽  
Vol 127 (5) ◽  
pp. 1435-1445 ◽  
Author(s):  
E A Connor ◽  
K Qin ◽  
H Yankelev ◽  
D DeStefano

Denervation of skeletal muscle results in dramatic remodeling of the cellular and molecular composition of the muscle connective tissue. This remodeling is concentrated in muscle near neuromuscular junctions and involves the accumulation of interstitial cells and several extracellular matrix molecules. Given the role of extracellular matrix in neurite outgrowth and synaptogenesis, we predict that this remodeling of the junctional connective tissue directly influences the regeneration of the neuromuscular junction. As one step toward understanding the role of this denervation-induced remodeling in synapse formation, we have begun to look for the signals that are involved in initiating the junctional accumulations of interstitial cells and matrix molecules. Here, the role of muscle inactivity as a signal was examined. The distributions of interstitial cells, fibronectin, and tenascin were determined in muscles inactivated by presynaptic blockade of muscle activity with tetrodotoxin. We found that blockade of muscle activity for up to 4 wk produced neither the junctional accumulation of interstitial cells nor the junctional concentrations of tenascin and fibronectin normally present in denervated frog muscle. In contrast, the muscle inactivity induced the extrajunctional appearance of two synapse-specific molecules, the acetylcholine receptor and a muscle fiber antigen, mAb 3B6. These results demonstrate that the remodeling of the junctional connective tissue in response to nerve injury is a unique response of muscle to denervation in that it is initiated by a mechanism that is independent of muscle activity. Thus connective tissue remodeling in denervated skeletal muscle may be induced by signals released from or associated with the nerve other than the evoked release of neurotransmitter.


2008 ◽  
Vol 9 (4) ◽  
pp. 311-317 ◽  
Author(s):  
Masao Mizuno ◽  
Gabrielle K Savard ◽  
Nils-Holger Areskog ◽  
Carsten Lundby ◽  
Bengt Saltin

2005 ◽  
Vol 54 (3) ◽  
pp. 5-11
Author(s):  
D. F. Kostyuchek ◽  
А. S. Gordeladze ◽  
А. S. Klyukovkina

Theclinical-morphological, immunohistochemical examination of the elongation of uterine cervix (EUC) in patients aged of 29-70 years old was conducted. The correlation of the systemic connective tissue dysplasia (SCTD) with the reconstruction of the tissue architectonics of the cervix, disorders of collagen synthesis, redistribution of the I, III and IV types of collagen was established, which testify the role of SCTD in the pathogenesis of the EUC.


Author(s):  
N.P. Burrows

The inherited disorders of connective tissue are all conditions in which structural defects in collagen or other extra cellular matrix proteins lead to its fragility, with the commonest sites of involvement being the skin, ligaments and vasculature. EDS is a heterogeneous group of disorders resulting from abnormalities in collagen synthesis and processing, or of other extracellular matrix proteins. They can be classified on the basis of descriptive clinical phenotype and/or underlying molecular cause. Most cases are autosomal dominant, but 30 to 50% may be sporadic....


2000 ◽  
Vol 279 (3) ◽  
pp. C724-C733 ◽  
Author(s):  
Bradley R. Fruen ◽  
Jennifer M. Bardy ◽  
Todd M. Byrem ◽  
Gale M. Strasburg ◽  
Charles F. Louis

Calmodulin (CaM) activates the skeletal muscle ryanodine receptor Ca2+ release channel (RyR1) in the presence of nanomolar Ca2+ concentrations. However, the role of CaM activation in the mechanisms that control Ca2+ release from the sarcoplasmic reticulum (SR) in skeletal muscle and in the heart remains unclear. In media that contained 100 nM Ca2+, the rate of45Ca2+ release from porcine skeletal muscle SR vesicles was increased approximately threefold in the presence of CaM (1 μM). In contrast, cardiac SR vesicle45Ca2+ release was unaffected by CaM, suggesting that CaM activated the skeletal RyR1 but not the cardiac RyR2 channel isoform. The activation of RyR1 by CaM was associated with an approximately sixfold increase in the Ca2+ sensitivity of [3H]ryanodine binding to skeletal muscle SR, whereas the Ca2+ sensitivity of cardiac SR [3H]ryanodine binding was similar in the absence and presence of CaM. Cross-linking experiments identified both RyR1 and RyR2 as predominant CaM binding proteins in skeletal and cardiac SR, respectively, and [35S]CaM binding determinations further indicated comparable CaM binding to the two isoforms in the presence of micromolar Ca2+. In nanomolar Ca2+, however, the affinity and stoichiometry of RyR2 [35S]CaM binding was reduced compared with that of RyR1. Together, our results indicate that CaM activates RyR1 by increasing the Ca2+ sensitivity of the channel, and further suggest differences in CaM's functional interactions with the RyR1 and RyR2 isoforms that may potentially contribute to differences in the Ca2+ dependence of channel activation in skeletal and cardiac muscle.


Author(s):  
Andrew Dunn ◽  
Madison Marcinczyk ◽  
Muhamed Talovic ◽  
Krishna Patel ◽  
Gabriel Haas ◽  
...  

2014 ◽  
Vol 1622 ◽  
pp. 189-195
Author(s):  
Anahita Khanlari ◽  
Tiffany C. Suekama ◽  
Michael S. Detamore ◽  
Stevin H. Gehrke

ABSTRACTChondroitin sulfate (CS) is one of the major glycosaminoglycans (GAGs) present in the connective tissue extracellular matrix (ECM) and is responsible for the regulation of cellular activities as well as providing mechanical support for the surrounding tissue. Due to presence of CS in the natural tissues including cartilage, hydrogels of CS and other GAGs have been widely used in cartilage regeneration. Due to their polyelectrolyte nature, GAG-based hydrogels are brittle and require modifications to overcome the weak mechanical properties. In this work, we showed copolymerization of methacrylated chondroitin sulfate with oligo(ethylene glycol)s improved the crosslink density of the gels from 2 to 20 times depending on the methacrylation degree of CS and length of the crosslinking monomer. Copolymerization of CS with oligo(ethylene glycol) acrylates is a method to design hydrogels with tunable swelling and mechanical properties.


Sign in / Sign up

Export Citation Format

Share Document