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

Abstract

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.

Gene expression profiling in patients with polymyalgia rheumatica before and after symptom-abolishing glucocorticoid treatment

“…Furthermore, indicating a minor role of inactivity in the present study, the number of genes in muscle influenced by PMR was small compared to findings in response to inactivity per se [27]. Another finding that may possibly contribute to the muscle complaints, primarily the muscle stiffness, experienced by PMR patients [28] is that proteins involved in organizing the cytoskeleton, including tubulin delta 1 (TUBD1; similar findings with microarrays and with qRT-PCR) and microtubule affinity-regulating kinase 4 (MARK4; similar differences in microarray and qRT-PCR, but only significant in the former), were upregulated in patients before prednisolone treatment (Tables 2 and 5) [28].…”

3‐D ultrastructure and collagen composition of healthy and overloaded human tendon: evidence of tenocyte and matrix buckling

“…Tendon tissue is comprised of a relatively small population of fibroblast-like cells (tenocytes) surrounded by an collagenous extracellular matrix (ECM) that comprises ~85% of the mass of mature tendon (reviewed by (Kjaer, 2004)). Tendon injuries represent a significant clinical problem, and details of the pathological changes in overloaded tendon and the associated development of tendinopathy are sparse (Arnoczky et al, 2007).…”

Increased skeletal muscle expression of VEGF induced by massage and exercise

“…Massage, applied in the form of nonspecific mechanical stimuli (e.g. muscle deformation in the direction transverse to the course of the muscle fibers), can stimulate mechanisms of mechanotransduction and cause many cellular responses in muscle fibers, including the expression of growth factors [17][18][19]. For instance, massage of muscle tendons while undergoing long-term, systematic running exercise resulted in increased expression of proangiogenic factors' genes, such as VEGF-A, FGF-2, and CD34 [20].…”