PGC-1α overexpression partially rescues impaired oxidative and contractile pathophysiology following volumetric muscle loss injury

Southern, W. M.; Nichenko, A. S.; Tehrani, K. F.; McGranahan, M. J.; Krishnan, L.; Qualls, A. E.; Jenkins, N. J.; Mortensen, L. J.; Yin, H.; Yin, A.; Guldberg, R. E.; Greising, S. M.; Call, J. A.

doi:10.1101/535328

bioRxiv · 10.1101/535328

PGC-1α overexpression partially rescues impaired oxidative and contractile pathophysiology following volumetric muscle loss injury

Southern, W. M.·Nichenko, A. S.·Tehrani, K. F.·McGranahan, M. J.·Krishnan, L.·Qualls, A. E.·Jenkins, N. J.·Mortensen, L. J.·Yin, H.·Yin, A.·Guldberg, R. E.·Greising, S. M.·Call, J. A.

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Abstract

Volumetric muscle loss (VML) injury is characterized by a non-recoverable loss of muscle fibers due to ablative surgery or severe orthopaedic trauma, that results in chronic functional impairments of the soft tissue. Currently, the effects of VML on the oxidative capacity and adaptability of the remaining injured muscle are unclear. A better understanding of this pathophysiology could significantly shape how VML-injured patients and clinicians approach regenerative medicine and rehabilitation following injury. Herein, the data indicated that VML-injured muscle has diminished mitochondrial content and function (i.e. oxidative capacity), loss of mitochondrial network organization, and attenuated oxidative adaptations to exercise. However, forced PGC-1 over-expression rescued the deficits in oxidative capacity and muscle strength. This implicates physiological activation of PGC1- as a limiting factor in VML-injured muscle adaptive capacity and provides a mechanistic target for regenerative rehabilitation approaches to address the skeletal muscle dysfunction.

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Southern, W. M., Nichenko, A. S., Tehrani, K. F., McGranahan, M. J., Krishnan, L., Qualls, A. E., Jenkins, N. J., Mortensen, L. J., Yin, H., Yin, A., Guldberg, R. E., Greising, S. M., Call, J. A.. 2019-01-31. PGC-1α overexpression partially rescues impaired oxidative and contractile pathophysiology following volumetric muscle loss injury. https://doi.org/10.1101/535328

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