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Electrical stimulation of hindlimb skeletal muscle has beneficial effects on sublesional bone in a rat model of spinal cord injury

Zhao, W, Peng, Y, Hu, Y, Guo, XE, Li, J, Cao, J, Pan, J, Feng, JQ, Cardozo, C, Jarvis, JC, Bauman, WA and Qin, W (2021) Electrical stimulation of hindlimb skeletal muscle has beneficial effects on sublesional bone in a rat model of spinal cord injury. Bone, 144. ISSN 8756-3282

Electrical Stimulation of Hindlimb Skeletal Muscle has Beneficial Effects on Sublesional Bone in a Rat Model of Spinal Cord Injury.pdf - Accepted Version
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Spinal cord injury (SCI) results in marked atrophy of sublesional skeletal muscle and substantial loss of bone. In this study, the effects of prolonged electrical stimulation (ES) and/or testosterone enanthate (TE) on muscle mass and bone formation in a rat model of SCI were tested. Compared to sham-transected animals, a significant reduction of the mass of soleus, plantaris and extensor digitorum longus (EDL) muscles was observed in animals 6 weeks post-SCI. Notably, ES or ES + TE resulted in the increased mass of the EDL muscles. ES or ES + TE significantly decreased mRNA levels of muscle atrophy markers (e.g., MAFbx and MurF1) in the EDL. Significant decreases in bone mineral density (BMD) (−27%) and trabecular bone volume (−49.3%) at the distal femur were observed in animals 6 weeks post injury. TE, ES and ES + TE treatment significantly increased BMD by +6.4%, +5.4%, +8.5% and bone volume by +22.2%, and +56.2% and+ 60.2%, respectively. Notably, ES alone or ES + TE resulted in almost complete restoration of cortical stiffness estimated by finite element analysis in SCI animals. Osteoblastogenesis was evaluated by colony-forming unit-fibroblastic (CFU-F) staining using bone marrow mesenchymal stem cells obtained from the femur. SCI decreased the CFU-F+ cells by −56.8% compared to sham animals. TE or ES + TE treatment after SCI increased osteoblastogenesis by +74.6% and +67.2%, respectively. An osteoclastogenesis assay revealed significantly increased TRAP+ multinucleated cells (+34.8%) in SCI animals compared to sham animals. TE, ES and TE + ES treatment following SCI markedly decreased TRAP+ cells by −51.3%, −40.3% and −46.9%, respectively. Each intervention greatly reduced the ratio of RANKL to OPG mRNA of sublesional long bone. Collectively, our findings demonstrate that after neurologically complete paralysis, dynamic muscle resistance exercise by ES reduced muscle atrophy, downregulated genes involved in muscle wasting, and restored mechanical loading to sublesional bone to a degree that allowed for the preservation of bone by inhibition of bone resorption and/or by facilitating bone formation.

Item Type: Article
Uncontrolled Keywords: Science & Technology; Life Sciences & Biomedicine; Endocrinology & Metabolism; Spinal cord injury; Electrical stimulation; Muscle; Bone; Muscle, Skeletal; Bone and Bones; Hindlimb; Animals; Rats; Spinal Cord Injuries; Electric Stimulation; Bone Density; Bone; Electrical stimulation; Muscle; Spinal cord injury; Animals; Bone Density; Bone and Bones; Electric Stimulation; Hindlimb; Muscle, Skeletal; Rats; Spinal Cord Injuries; 06 Biological Sciences; 09 Engineering; 11 Medical and Health Sciences; Endocrinology & Metabolism
Subjects: R Medicine > RC Internal medicine > RC1200 Sports Medicine
Divisions: Sport & Exercise Sciences
Publisher: Elsevier
SWORD Depositor: A Symplectic
Date Deposited: 16 Jun 2022 10:46
Last Modified: 16 Jun 2022 11:00
DOI or ID number: 10.1016/j.bone.2020.115825
URI: https://researchonline.ljmu.ac.uk/id/eprint/17085
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