The MRL/MpJ Mouse Strain Is Not Protected From Muscle Atrophy and Weakness After Rotator Cuff Tear

Abstract

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

Identification of Diagnostic Biomarkers Associated with Stromal and Immune Cell Infiltration in Fatty Infiltration After Rotator Cuff Tear by Integrating Bioinformatic Analysis and Machine-Learning

“…The RNA-seq count datasets of GSE130447 36 and GSE103266 37 were downloaded from GEO database, which were based on GPL17021 Illumina HiSeq 2500 (Mus musculus) platform and GPL18694 Illumina HiSeq 2500 (Rattus norvegicus) platform, respectively. GSE130447 dataset contains sixteen infraspinatus muscle samples collected from C57BL/6J (B6) and MRL/MpJ (MRL) mice, including eight fatty infiltrated samples established by a full-thickness infraspinatus tendon tear and eight control samples.…”