Effect of treadmill exercise combined with bone marrow stromal cell transplantation on atrophy-related signaling pathway in the denervated soleus muscle

Author:

Cho Yeong-Hyun,Seo Tae-BeomORCID

Abstract

The purpose of this study was to investigate whether combination of low-intensity exercise with bone marrow stromal cell (BMSC) transplantation could regulate protein kinas B (Akt)- mammalian target of rapamycin (mTOR) and Wnt3a-β-catenin signaling pathways for prevention of soleus muscle atrophy after sciatic nerve injury (SNI). The experimental rats divided into 5 groups (n= 10): normal control group, SNI+sedentary group (SED), SNI+low-intensity treadmill exercise group (TEX), SNI+BMSC transplantation group (BMSC), SNI+TEX+BMSC transplantation group (TEX+BMSC). Sciatic nerve crush injury was applied into the middle of thigh twice for 1 min and 30 sec at interval. Low-intensity treadmill exercise was comprised of walking at a speed of 4 to 8 m/min for 30 min once a day. cultured BMSC at a density of 5× 106 in 50-μL phosphate-buffered saline was injected into the distal portion of the injured sciatic nerves. TEX+BMSC group dramatically upregulated expression levels of growth-associated protein-43 in the injured sciatic nerve at 2 weeks postinjury. Also, although Akt and mTOR signaling pathway significantly increased in TEX and BMSC groups than SED group, TEX+BMSC group showed more potent increment on this signaling in soleus muscle after SNI. Lastly, Wnt3a and the nuclear translocation of β-catenin and nuclear factor-kappa B in soleus were increased by SNI, but TEX+BMSC group significantly downregulated activity of this signaling pathway in the nuclear cell lysate of soleus muscle. Present findings provide new information that combination of low-intensity treadmill exercise might be effective therapeutic approach on restriction of soleus muscle atrophy after peripheral nerve injury.

Funder

National Research Foundation of Korea

Ministry of Science and ICT

Publisher

Korean Society of Exercise Rehabilitation

Subject

Orthopedics and Sports Medicine,Physical Therapy, Sports Therapy and Rehabilitation

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