Striated muscle fiber apoptosis after experimental tendon lesion in a rat model

Abstract

Tendon lesions induce muscular atrophy, the nature of which has not yet been clearly related to lesion etiology and entity. In the present study, tendon and muscle alterations were assessed after experimental tendon lesion of the Infraspinatus muscle in young rats. The consequences of lesions differed on the basis of both extension and injured tissue vascularization, that is apoptosis and/or degeneration, differing mainly by energy demands: apoptosis requires high energy levels (proportional to vascular supply), but degeneration does not. It is well known that tendons are poorly supplied with blood compared with muscular masses, which are abundantly vascularized. Five weeks after tendon surgical section, tendon/muscle samples were taken for TUNEL and transmission electron microscopy. The structural results reported here identified different tendon/muscle alterations: degeneration of tendon without signs of apoptosis, and atrophy of muscle fibers due only to apoptosis. This led to the formulation of the following hypothetical sequence of events: a tendon lesion, not recovering quickly due to the poor tendon blood supply, results in degeneration of the injured tendon, which, in turn, induces a partial disuse of the muscle mass, which consequently atrophies (proportionally to the severity of tendon lesion) by striated muscular fiber apoptosis. The authors suggest that the different behavior of the two tissues depends on the marked difference in their vascularization.

The myonuclear domain is not maintained in skeletal muscle during either atrophy or programmed cell death

“…In contrast, skeletal muscle atrophy is accompanied by a dramatic increase in the number of apoptotic nuclei within the tissue (3,4,7,15,56,74,78). This apoptosis can occur in a caspase-dependent (48) or -independent (1,43) manner and results in the loss of large numbers of nuclei.…”

Skeletal Muscles Do Not Undergo Apoptosis During Either Atrophy or Programmed Cell Death-Revisiting the Myonuclear Domain Hypothesis

“…There are many interventions that induce atrophy in animal models, including: immobilization, denervation, and sepsis (Fitts et al., 1986; Minnaard et al., 2005; O’Leary et al., 2012). In each case, there is a net loss of both muscle cross-sectional area (the primary assay) and the appearance of apoptotic cells within the tissue (McCall et al., 1998; Smith et al., 2000; Strasser et al., 2000; Alway et al., 2003; McClung et al., 2007; Andrianjafiniony et al., 2010; Guo et al., 2012; Palumbo et al., 2012; Barnes et al., 2015; Cheema et al., 2015; Li et al., 2016; Kletzien et al., 2018). In these studies, apoptosis is measured in a variety of methods, including caspase activation, mitochondrial EndoG release, or DNA fragmentation [which is detected anatomically with terminal deoxynucleotidyl transferase (TdT) dUTP Nick-End Labeling (TUNEL) staining or biochemically by visualizing DNA ladders via agarose gel electrophoresis].…”

Skeletal Muscles Do not Undergo Apoptosis During Either Atrophy or Programmed Cell Death

“…There are many interventions that induce atrophy in animal models, including: immobilization, denervation, and sepsis [21][22][23]. In each case, there is a net loss of both muscle cross-sectional area (the primary metric) and the appearance of apoptotic cells within the tissue [24][25][26][27][28][29][30][31][32][33][34]. These authors measured apoptosis with a variety of assays, including: caspase activation, EndoG release from mitochondria, and DNA fragmentation as measured anatomically with Terminal deoxynucleotidyl transferase (TdT) dUTP Nick-End Labeling (TUNEL) staining or biochemically by visualizing DNA ladders via agarose gel electrophoresis.…”