Nandrolone supplementation does not improve functional recovery in an aged animal model of volumetric muscle loss injury
John T. Kim
Department of Biomedical Engineering, University of Arkansas, Fayetteville, Arkansas, USA
Search for more papers by this authorKevin Roberts
Department of Biomedical Engineering, University of Arkansas, Fayetteville, Arkansas, USA
Search for more papers by this authorGrady Dunlap
Department of Biomedical Engineering, University of Arkansas, Fayetteville, Arkansas, USA
Search for more papers by this authorRichard Perry
Department of Health, Human Performance, and Recreation, College of Education and Health Professions, University of Arkansas, Fayetteville, Arkansas, USA
Search for more papers by this authorTyrone Washington
Department of Health, Human Performance, and Recreation, College of Education and Health Professions, University of Arkansas, Fayetteville, Arkansas, USA
Search for more papers by this authorCorresponding Author
Jeffrey C. Wolchok
Department of Biomedical Engineering, University of Arkansas, Fayetteville, Arkansas, USA
Correspondence
Jeffrey C. Wolchok, Department of Biomedical Engineering, University of Arkansas, John A. White, Jr. Engineering Hall, Suite 120, Fayetteville, AR 72701, USA.
Email: [email protected]
Search for more papers by this authorJohn T. Kim
Department of Biomedical Engineering, University of Arkansas, Fayetteville, Arkansas, USA
Search for more papers by this authorKevin Roberts
Department of Biomedical Engineering, University of Arkansas, Fayetteville, Arkansas, USA
Search for more papers by this authorGrady Dunlap
Department of Biomedical Engineering, University of Arkansas, Fayetteville, Arkansas, USA
Search for more papers by this authorRichard Perry
Department of Health, Human Performance, and Recreation, College of Education and Health Professions, University of Arkansas, Fayetteville, Arkansas, USA
Search for more papers by this authorTyrone Washington
Department of Health, Human Performance, and Recreation, College of Education and Health Professions, University of Arkansas, Fayetteville, Arkansas, USA
Search for more papers by this authorCorresponding Author
Jeffrey C. Wolchok
Department of Biomedical Engineering, University of Arkansas, Fayetteville, Arkansas, USA
Correspondence
Jeffrey C. Wolchok, Department of Biomedical Engineering, University of Arkansas, John A. White, Jr. Engineering Hall, Suite 120, Fayetteville, AR 72701, USA.
Email: [email protected]
Search for more papers by this authorAbstract
Aging hinders the effectiveness of regenerative medicine strategies targeting the repair of volumetric muscle loss (VML) injury. Anabolic steroids have been shown to improve several factors which contribute to the age-related decline in muscle's regenerative capacity. In this study, the impact of exogenous nandrolone decanoate (ND) administration on the effectiveness of a VML regenerative repair strategy was explored using an aged animal model. Unilateral tibialis anterior VML injuries were repaired in 18-month-aged animal models (male Fischer 344 rat) using decellularized human skeletal muscle scaffolds supplemented with autologous minced muscle. The contralateral limb was left untreated/uninjured. Following repair, ND(+) or a carrier control (ND−) was delivered via weekly injection for a period of 8 weeks. At 8 weeks, muscle isometric torque, gene expression, and tissue structure were assessed. ND(+) treatment did not improve contractile torque recovery following VML repair when compared to carrier only ND(−) injection controls. Peak isometric torque in the ND(+) VML repair group remained significantly below contralateral uninjured control values (4.69 ± 1.18vs. 7.46 ± 1.53 N mm/kg) and was statistically indistinguishable from carrier only ND(−) VML repair controls (4.47 ± 1.18 N mm/kg). Gene expression for key myogenic genes (Pax7, MyoD, MyoG, IGF-1) were not significantly elevated in response to ND injection, suggesting continued age related myogenic impairment even in the presence of ND(+) treatment. ND injection did reduce the histological appearance of fibrosis at the site of VML repair, and increased expression of the collagen III gene, suggesting some positive effects on repair site matrix regulation. Overall, the results presented in this study suggest that a decline in regenerative capacity with aging may present an obstacle to regenerative medicine strategies targeting VML injury and that the delivery of anabolic stimuli via ND administration was unable to overcome this decline.
CONFLICT OF INTEREST
The authors have declared that there is no conflict of interes
Open Research
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available from the corresponding author upon reasonable request.
Supporting Information
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| term3286-sup-0001-fig_s1.tif133.4 KB | Figure S1 |
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