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Chronic rotator cuff tears are a common source of shoulder pain and disability. Patients with rotator cuff tears often have substantial weakness, fibrosis, and fat accumulation, which limit successful surgical repair and postoperative rehabilitation. The Murphy Roths Large (MRL) strain of mice have demonstrated superior healing and protection against pathological changes in several disease and injury conditions. We tested the hypothesis that, compared with the commonly used C57Bl/6 (B6) strain, MRL mice would have less muscle fiber atrophy and fat accumulation, and be protected against the loss in force production that occurs after cuff tear. Adult male B6 and MRL mice were subjected to a rotator cuff tear, and changes in muscle fiber contractility and histology were measured. RNA sequencing and shotgun metabolomics and lipidomics were also performed. The muscles were harvested one month after tear. B6 and MRL mice had a 40% reduction in relative muscle force production after rotator cuff tear. RNA sequencing identified an increase in fibrosis-associated genes and a reduction in mitochondrial metabolism genes. The markers of glycolytic metabolism increased in B6 mice, while MRL mice appeared to increase amino acid metabolism after tear. There was an accumulation of lipid after injury, although there was a divergent response between B6 and MRL mice in the types of lipid species that accrued. There were strain-specific differences between the transcriptome, metabolome, and lipidome of B6 and MRL mice, but these differences did not protect MRL mice from weakness and pathological changes after rotator cuff tear. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:811-822, 2020.

Introduction Patients with anterior cruciate ligament (ACL) tears have persistent quadriceps strength deficits that are thought to be due to altered neurophysiological function. Our goal was to determine the changes in muscle fiber contractility independent of the ability of motor neurons to activate fibers. Methods We obtained quadriceps biopsies of patients undergoing ACL reconstruction, and additional biopsies 1, 2, and 6 months after surgery. Muscles fiber contractility was assessed in vitro, along with whole muscle strength testing. Results Compared with controls, patients had a 30% reduction in normalized muscle fiber force at the time of surgery. One month later, the force deficit was 41%, and at 6 months the deficit was 23%. Whole muscle strength testing demonstrated similar trends. Discussion While neurophysiological dysfunction contributes to whole muscle weakness, there is also a reduction in the force generating capacity of individual muscle cells independent of alpha motor neuron activation. Muscle Nerve, 2018.

Chronic rotator cuff tears are a common source of shoulder pain and disability. Patients with rotator cuff tears often have substantial weakness, fibrosis, and fat accumulation which limit successful surgical repair and postoperative rehabilitation. The Murphy Roths Large (MRL) strain of mice have demonstrated superior healing and protection against pathological changes in several disease and injury conditions. We tested the hypothesis that, compared to the commonly used C57Bl/6 (B6) strain, MRL mice would have less muscle fiber atrophy and fat accumulation, and be protected against the loss in force production that occurs after cuff tear. Adult male mice B6 and MRL mice were subjected to a rotator cuff tear, and changes in muscle fiber contractility and histology were measured. RNA sequencing, and shotgun metabolomics and lipidomics were also performed. Muscles were harvested one month after tear. B6 and MRL mice had a 40% reduction in relative muscle force production after rotator cuff tear. RNA sequencing identified an increase in fibrosis-associated genes and a reduction in mitochondrial metabolism genes. Markers of glycolytic metabolism increased in B6 mice, while MRL mice appeared to increase amino acid metabolism after tear. There was an accumulation of lipid after injury, although there was a divergent response between B6 and MRL mice in the types of lipid species that accrued. There were strain-specific differences between the transcriptome, metabolome, and lipidome of B6 and MRL mice, but these differences did not protect MRL mice from weakness and pathological changes after rotator cuff tear.

Patients with anterior cruciate ligament (ACL) tears have persistent quadriceps strength deficits that are thought to be due to altered neurophysiological function. Our goal was to determine the changes in muscle fiber contractility independent of the ability of motor neurons to activate fibers.We obtained quadriceps biopsies of patients undergoing ACL reconstruction, and additional biopsies 1, 2, and 6 months after surgery. Muscles fiber contractility was assessed in vitro, along with whole muscle strength testing.Compared with controls, patients had a 30% reduction in normalized muscle fiber force at the time of surgery. One month later, the force deficit was 41%, and at 6 months the deficit was 23%. Whole muscle strength testing demonstrated similar trends.While neurophysiological dysfunction contributes to whole muscle weakness, there is also a reduction in the force generating capacity of individual muscle cells independent of alpha motor neuron activation. Muscle Nerve, 2018.