Muscle regeneration potential and satellite cell activation profile during recovery following hindlimb immobilization in mice

Abstract

Reduced muscle activity leads to muscle atrophy and function loss in patients and animal models. Satellite cells (SCs) are postnatal muscle stem cells that play a pivotal role in skeletal muscle regeneration following injury. The regenerative potential, satellite cell numbers, and markers during recovery following immobilization of the hindlimb for 7 days were explored. In mice exposed to 7 days of hindlimb immobilization, in those exposed to recovery (7 days, splint removal), and in contralateral control muscles, muscle precursor cells were isolated from all hindlimb muscles (fluorescence-activated cell sorting, FACS) and SCs, and muscle regeneration were identified using immunofluorescence (gastrocnemius and soleus) and electron microscopy (EM, gastrocnemius). Expression of ki67, pax7, myoD, and myogenin was quantified (RT-PCR) from SC FACS yields. Body and grip strength were determined. Following 7 day hindlimb immobilization, a decline in SCs (FACS, immunofluorescence) was observed together with an upregulation of SC activation markers and signs of muscle regeneration including fusion to existing myofibers (EM). Recovery following hindlimb immobilization was characterized by a program of muscle regeneration events. Hindlimb immobilization induced a decline in SCs together with an upregulation of markers of SC activation, suggesting that fusion to existing myofibers takes place during unloading. Muscle recovery induced a significant rise in muscle precursor cells and regeneration events along with reduced SC activation expression markers and a concomitant rise in terminal muscle differentiation expression. These are novel findings of potential applicability for the treatment of disuse muscle atrophy, which is commonly associated with severe chronic and acute conditions.

Expression Levels of Long Non-Coding RNAs Change in Models of Altered Muscle Activity and Muscle Mass

“…Hindlimb suspension and fasting treatments impair satellite cell proliferation [77,78]. Immobilization decreases the number of satellite cells, whereas it increases the markers of satellite cell activation [79]. Satellite cells play little or no role in muscle hypertrophy induced by myostatin deficiency [80].…”

Satellite Cells and Markers of Muscle Regeneration during Unloading and Reloading: Effects of Treatment with Resveratrol and Curcumin

“…Disuse muscle atrophy is an important condition that is the result of progression of other chronic and acute diseases, such as cardiac and respiratory disorders; cancer; prolonged bed rest; and critical illness. Reduced physical activity leading to deconditioning is characterized by the loss of muscle mass and function in the affected muscles in patients [ 1 , 2 , 3 , 4 , 5 ] and in animal models [ 6 , 7 , 8 ]. Muscle atrophy resulting from deconditioning may also worsen disease prognosis in patients with chronic and acute diseases regardless of the underlying condition [ 9 , 10 ].…”

“…Several pathophysiological and biological mechanisms are involved in the loss of muscle mass and function characteristic of muscle atrophy. In this regard, a great many studies have previously demonstrated that markers of oxidative stress, inflammation, proteolysis, apoptosis, autophagy, and atrophy signaling pathways were upregulated in the atrophying muscles following periods of disuse in patients [ 11 , 12 ] and animal models [ 6 , 7 , 8 ]. Whether regenerative potential is altered in models of disuse muscle atrophy remains to be fully elucidated.…”

Chronic Alcohol Dysregulates Skeletal Muscle Myogenic Gene Expression after Hind Limb Immobilization in Female Rats

“…In vitro findings also demonstrate that alcohol suppresses myoblast fusion under differentiation conditions [23,24,39,40]. In mice, MyoD mRNA was significantly increased after seven days of immobilization and went back to control levels by seven days of post-immobilization recovery [41]. In the present study, MyoD was decreased with alcohol at three days compared to pair-fed animals and increased after 14 days of post-immobilization recovery, suggesting that alcohol may delay a normal early increase in MyoD expression or may prolong the regeneration process such that expression in the immobilized hind limb was much higher than for pair-fed animals at two weeks post-immobilization.…”