measurement-maximum-isometric-force-generated-permeabilized-skeletal

Measurement of Maximum Isometric Force Generated by Permeabilized Skeletal Muscle Fibers

Analysis of the contractile properties of chemically skinned, or permeabilized, skeletal muscle fibers offers a powerful means by which to assess muscle ...

University of Michigan Medical School

Rotator cuff tears are one of the most common musculoskeletal complaints and a substantial source of morbidity in elderly patients. Chronic cuff tears are associated with muscle atrophy and an infiltration of fat to the area, a condition known as "fatty degeneration." To improve the treatment of cuff tears in elderly patients, a greater understanding of the changes in the contractile properties of muscle fibers and the molecular regulation of fatty degeneration is essential.

Aging-associated exacerbation in fatty degeneration and infiltration after rotator cuff tear.

D&eacute;chirures de la coiffe des rotateurs sont une des plaintes musculo-squelettiques plus courantes et une source importante de morbidit&eacute; chez les patients &acirc;g&eacute;s. Des rotateurs chroniques sont associ&eacute;es &agrave; une atrophie musculaire et une infiltration de graisse dans la r&eacute;gion, une condition connue comme la &laquo; d&eacute;g&eacute;n&eacute;rescence graisseuse. &raquo; Pour am&eacute;liorer le traitement des rotateurs chez les patients &acirc;g&eacute;s, une meilleure compr&eacute;hension des changements dans les propri&eacute;t&eacute;s contractiles des fibres musculaires et de la r&eacute;gulation mol&eacute;culaire de la d&eacute;g&eacute;n&eacute;rescence graisseuse est essentielle.

Associ&eacute;s au vieillissement exacerbation d&eacute;g&eacute;n&eacute;rescence graisseuse et infiltration apr&egrave;s d&eacute;chirure de la coiffe des rotateurs.

A persistent atrophy of muscle fibers and an accumulation of fat, collectively referred to as fatty degeneration, commonly occur in patients with chronic rotator cuff tears. The etiology of fatty degeneration and function of the residual rotator cuff musculature have not been well characterized in humans. We hypothesized that muscles from patients with chronic rotator cuff tears have reduced muscle fiber force production, disordered myofibrils, and an accumulation of fat vacuoles.

Reduced muscle fiber force production and disrupted myofibril architecture in patients with chronic rotator cuff tears.

The repair and restoration of function after chronic rotator cuff tears are often complicated by muscle atrophy, fibrosis, and fatty degeneration of the diseased muscle. The inflammatory response has been implicated in the development of fatty degeneration after cuff injuries. Licofelone is a novel anti-inflammatory drug that inhibits 5-lipoxygenase (5-LOX), as well as cyclooxygenase (COX)-1 and COX-2 enzymes, which play important roles in inducing inflammation after injuries. While previous studies have demonstrated that nonsteroidal anti-inflammatory drugs and selective inhibitors of COX-2 (coxibs) may prevent the proper healing of muscles and tendons, studies about bone and cartilage have demonstrated that drugs that inhibit 5-LOX concurrently with COX-1 and COX-2 may enhance tissue regeneration.

Inhibition of 5-LOX, COX-1, and COX-2 increases tendon healing and reduces muscle fibrosis and lipid accumulation after rotator cuff repair.

Myostatin is a negative regulator of skeletal muscle and tendon mass. Myostatin deficiency has been well studied in mice, but limited data are available on how myostatin regulates the structure and function of muscles and tendons of larger animals. We hypothesized that, in comparison to wild-type (MSTN(+/+) ) rats, rats in which zinc finger nucleases were used to genetically inactivate myostatin (MSTN(Δ/Δ) ) would exhibit an increase in muscle mass and total force production, a reduction in specific force, an accumulation of type II fibres and a decrease and stiffening of connective tissue. Overall, the muscle and tendon phenotype of myostatin-deficient rats was markedly different from that of myostatin-deficient mice, which have impaired contractility and pathological changes to fibres and their extracellular matrix. Extensor digitorum longus and soleus muscles of MSTN(Δ/Δ) rats demonstrated 20-33% increases in mass, 35-45% increases in fibre number, 20-57% increases in isometric force and no differences in specific force. The insulin-like growth factor-1 pathway was activated to a greater extent in MSTN(Δ/Δ) muscles, but no substantial differences in atrophy-related genes were observed. Tendons of MSTN(Δ/Δ) rats had a 20% reduction in peak strain, with no differences in mass, peak stress or stiffness. The general morphology and gene expression patterns were similar between tendons of both genotypes. This large rodent model of myostatin deficiency did not have the negative consequences to muscle fibres and extracellular matrix observed in mouse models, and suggests that the greatest impact of myostatin in the regulation of muscle mass may not be to induce atrophy directly, but rather to block hypertrophy signalling.

Stuart M. Roche

Department of Orthopaedic Surgery

University of Michigan Medical School

Measurement of Maximum Isometric Force Generated by Permeabilized Skeletal Muscle Fibers