Estrogen modulates the skeletal muscle regeneration process and myotube morphogenesis: morphological analysis in mice with a low estrogen status

The purpose of this study was to elucidate the functions of estrogen and two estrogen receptors (ERs; ERα and ERβ) in the myoregeneration process and morphogenesis. Cardiotoxin (CTX) was injected into the tibialis anterior (TA) muscles of ovariectomized (OVX) mice to induce muscle injury, and subsequent myoregeneration was morphologically assessed. The diameter of regenerated myotubes in OVX mice was significantly smaller than that in intact mice at all time points of measurement. OVX mice also showed lower muscle recovery rates and slower speeds than did intact mice. ER protein levels showed a predominance of ERβ over ERα in both intact and OVX states. The ERβ level was increased significantly at 7 days after CTX injection in OVX mice and remained at a high level until 14 days. In addition, continuous administration of E2 to OVX mice in which muscle injury was induced resulted in a significantly larger diameter of regenerated myotubes than that in mice that did not receive estrogen. The results indicate that estrogen is an essential factor in the myoregeneration process since estrogen depletion delayed myoregeneration in injured muscles and administration of estrogen under the condition of a low estrogen status rescued delayed myoregeneration. The results strongly suggested that ERβ may be a factor that promotes myoregeneration more than does ERα.     

Absence of estrogen receptors delays myoregeneration and leads to intermuscular adipogenesis in a low estrogen status: Morphological comparisons in estrogen receptor alpha and beta knock out mice

This study aimed to investigate the function of estrogen receptors (ERs) in myoregeneration and intermuscular adipogenesis. Ovariectomized (OVX) ERα knockout (KO) mice and ERβ KO mice were used to assess the effect of estrogen on the myoregenerative process. Tibialis anterior muscle was collected on days 7, 10, and 14 after cardiotoxin injection to assess myotube morphology and adipogenesis area. Regenerated myotubes from OVX-ERβ KO mice were consistently smaller in diameter than those from OVX-ERα KO and OVX-wild-type mice, whereas the adipogenesis area of OVX-ERβ KO mice was consistently greater than that of the other types. Therefore, ERβ may be an influential factor in promoting myoregeneration and adipogenesis inhibition compared to ERα.