The Effect of Sclerostin on Myotropic Response to Exercise

Abstract

This study is the first to examine the effect of exogenous sclerostin injection on myotropic responses to sedentary behaviour and an aerobic exercise intervention. Specifically, changes in myosin heavy chain isoform distribution, muscle mass and myofiber cross sectional area were studied in response to sedentary behaviour and to a 5-week aerobic exercise intervention. Mice (n=24) were assigned to either remain sedentary (SED, n=24), or assigned to a 4-week exercise training program (EXT, n=24) and further spit into their final groupings with sedentary control (SED+C) and exercise control (EXT+C) groups receiving saline injections and sedentary sclerostin (SED+S) and exercise sclerostin (EXT+S) groups recombinant sclerostin. Soleus and extensor digitorum longus muscle were then extracted and analyzed via fluorescent immunohistochemistry and Western blotting. Sclerostin injection led to a significant reduction in soleus MHCI, MHC1/IIA, MHCIIA/X and MHC IIB cross-sectional area (p < .5) along with trending declines in MHC IIA (p = .1). In contrast to this, there was no effect of sclerostin injection on MHC IIX or MHCIIXB CSA. In EDL tissue there was a trend towards a decrease in tissue necropsy weight in the sclerostin injection group (p = .1). Sclerostin appeared to have no effect on total MHC protein content or in the examined markers of Wnt signaling (GSK3β, β-catenin) as detected in both soleus and EDL muscle tissue via western blot. Our findings demonstrate that sclerostin negatively influences muscle tissue via decreases in myofibril cross-sectional area and these decreases trend towards a significant reduction in muscle mass.