Relationship between fatty infiltration and gene expression in patients with medium rotator cuff tear

2020 ◽  
Author(s):  
Se-Young Ki ◽  
Yong-Soo Lee ◽  
Ja-Yeon Kim ◽  
Taewoo Lho ◽  
Seok Won Chung
Keyword(s):  
Gene Expression ◽  
Rotator Cuff ◽  
Rotator Cuff Tear ◽  
Fatty Infiltration ◽  
Cuff Tear

Retinoic Acid Receptor Agonists Suppress Muscle Fatty Infiltration in Mice

2021 ◽  
Vol 49 (2) ◽  
pp. 332-339
Author(s):  
Hideyuki Shirasawa ◽  
Noboru Matsumura ◽  
Masaki Yoda ◽  
Kazumasa Okubo ◽  
Masayuki Shimoda ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Rotator Cuff ◽  
Rotator Cuff Tear ◽  
Gene Expression Analysis ◽  
Retinoic Acid Receptor ◽  
Adipogenic Differentiation ◽  
Fatty Infiltration ◽  
Cuff Tear

Background: The infiltration of fat tissue into skeletal muscle, a condition referred to as muscle fatty infiltration or fatty degeneration, is regarded as an irreversible event that significantly compromises the motor function of skeletal muscle. Purpose: To investigate the effect of retinoic acid receptor (RAR) agonists in suppressing the adipogenic differentiation of fibroadipogenic progenitors (FAPs) in vitro and fatty infiltration after rotator cuff tear in mice. Study Design: Controlled laboratory study. Methods: FAPs isolated from mouse skeletal muscle were cultured in adipogenic differentiation medium in the presence or absence of an RAR agonist. At the end of cell culture, adipogenic differentiation was evaluated by gene expression analysis and oil red O staining. A mouse model of fatty infiltration—which includes the resection of the rotator cuff, removal of the humeral head, and denervation the supraspinatus muscle—was used to induce fatty infiltration in the supraspinatus muscle. The mice were orally or intramuscularly administered with an RAR agonist after the surgery. Muscle fatty infiltration was evaluated by histology and gene expression analysis. Results: RAR agonists effectively inhibited the adipogenic differentiation of FAPs in vitro. Oral and intramuscular administration of RAR agonists suppressed the development of muscle fatty infiltration in the mice after rotator cuff tear. In accordance, we found a significant decrease in the number of intramuscular fat cells and suppressed expression in adipogenic markers. RAR agonists also increased the expression of the transcripts for collagens; however, an accumulation of collagenous tissues was not histologically evident in the present model. Conclusion: Muscle fatty infiltration can be alleviated by RAR agonists through suppressing the adipogenic differentiation of FAPs. The results also suggest that RAR agonists are potential therapeutic agents for treating patients who are at risk of developing muscle fatty infiltration. The consequence of the increased expression of collagen transcripts by RAR agonists needs to be clarified. Clinical Relevance: RAR agonists can be used to prevent the development of muscle fatty infiltration after rotator cuff tear. Nevertheless, further studies are mandatory in a large animal model to examine the safety and efficacy of intramuscular injection of RAR agonists.

scholarly journals Gene Expression Patterns Analysis in the Supraspinatus Muscle after a Rotator Cuff Tear in a Mouse Model

2018 ◽  
Vol 2018 ◽  
pp. 1-18 ◽  
Author(s):  
Yong-Soo Lee ◽  
Ja-Yeon Kim ◽  
Hyo-Nam Kim ◽  
Dhong-Won Lee ◽  
Seok Won Chung
Keyword(s):  
Gene Expression ◽  
Rotator Cuff ◽  
Rotator Cuff Tear ◽  
Expression Patterns ◽  
Fatty Infiltration ◽  
Rna Isolation ◽  
Muscle Physiology ◽  
Fatty Acid Transport ◽  
Muscle Degeneration ◽  
Cuff Tear

Rotator cuff tear is a muscle-tendinous injury representative of various musculoskeletal disorders. In general, rotator cuff tear occurs in the tendon, but it causes unloading of the muscle resulting in muscle degeneration including fatty infiltration. These muscle degenerations lead to muscle weakness, pain, and loss of shoulder function and are well known as important factors for poor functional outcome after rotator cuff repair. Given that rotator cuff tear in various animal species results in similar pathological changes seen in humans, the animal model can be considered a good approach to understand the many aspects of the molecular changes in injured muscle. To comprehensively analyze changes in gene expression with time following a rotator cuff tear, we established a rotator cuff tear in mouse supraspinatus tendon of shoulder. At weeks 1 and 4 after the tear, the injured muscles were harvested for RNA isolation, and microarray analysis was performed. Expression patterns of genes belonging to 10 muscle physiology-related categories, including aging, apoptosis, atrophy, and fatty acid transport, were analyzed and further validated using real-time PCR. A total of 39,429 genes were analyzed, and significant changes in expression were observed for 12,178 genes at 1 week and 2,370 genes at 4 weeks after the tear. From the list of top 10 significantly up- and downregulated genes at the 2 time periods and the network evaluation of relevant genes according to the 10 categories, several important genes in each category were observed. In this study, we found that various genes are significantly altered after rotator cuff tear, and these genes may play key roles in controlling muscle degeneration after a rotator cuff tear.

Rotator Cuff Tear Size Regulates Fibroadipogenic Progenitor Number and Gene Expression Profile in the Supraspinatus Independent of Patient Age

2021 ◽  
pp. 036354652110545
Author(s):  
Michael R. Davies ◽  
Hannah Chi ◽  
Gurbani Kaur ◽  
Mengyao Liu ◽  
C. Benjamin Ma ◽  
...  
Keyword(s):  
Gene Expression ◽  
Rotator Cuff ◽  
Rotator Cuff Tear ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Patient Age ◽  
Cuff Tear ◽  
Patient Âgé ◽  
Beige Adipocytes ◽  
Tear Size

Background: Fatty infiltration of rotator cuff muscle is a limiting factor in the success of repairs. Fibroadipogenic progenitors (FAPs) are a population of stem cells within the rotator cuff that can differentiate into white adipocytes, fibroblasts, and beige adipocytes. The effects of patient age and rotator cuff tendon tear size on the number, differentiation patterns, and gene expression profiles of FAPs have not yet been analyzed. Purpose: To determine if patient age and rotator cuff tear size independently regulate FAP number, differentiation patterns, and gene expression profiles. Study Design: Controlled laboratory study. Methods: Supraspinatus muscle samples were collected from 26 patients between the ages of 42 and 76 years with partial- or full-thickness rotator cuff tears. FAPs were quantified using fluorescence-activated cell sorting. Gene expression analysis was performed across a custom 96-gene panel using NanoString. In vitro differentiation assays of FAPs were conducted using adipogenic, fibrogenic, and beige-inducing (amibegron-treated) media, and quantitative polymerase chain reaction was used to assess gene expression differences between adipogenic and amibegron media conditions. Multivariable linear regressions were performed using Stata to independently analyze the effects of age and rotator cuff tear size on FAP number, differentiation, and gene expression. Results: Increasing age and tear size were independently correlated with increased FAP number (βage = 0.21, P = .03; βtear size = 3.86, P = .05). There was no clear association between age and gene expression of freshly sorted FAPs. Under adipogenic and fibrogenic media conditions, increasing age and tear size were independently associated with increased adipogenic and fibrogenic differentiation of FAPs. Under amibegron treatment conditions, age positively correlated with increased beige differentiation (β = 1.03; P < .0001), while increasing tear size showed a trend toward decreased beige differentiation (β = −4.87; P = .1). When gene expression patterns between adipogenic and amibegron media conditions were compared, larger tear size strongly inhibited beige gene expression, while advanced age did not. Conclusion: Patient age and rotator cuff tear size independently regulated FAP number, differentiation, and gene expression. Age and tear size were positively correlated with increased FAP number and fibrogenic/adipogenic differentiation. Advancing patient age did not limit FAP beige differentiation and gene expression, while increasing rotator cuff tear size strongly inhibited these processes.

Effect of hypercholesterolemia on fatty infiltration and rotator cuff healing in a chronic rotator cuff tear model of rabbit

2016 ◽  
Vol 25 (6) ◽  
pp. e188
Author(s):  
Joo Han Oh ◽  
Seok Won Chung ◽  
HaeBong Park ◽  
Jieun Kwon ◽  
Ghee Young Choe
Keyword(s):  
Rotator Cuff ◽  
Rotator Cuff Tear ◽  
Fatty Infiltration ◽  
Cuff Tear

PARP-1 knock-out leads to regeneration and decreased fatty infiltration in the muscle after artificial rotator cuff tear in a mouse model

2016 ◽  
Vol 25 (10) ◽  
pp. e316
Author(s):  
Michael Kuenzler ◽  
Katja Nuss ◽  
Agnieszka Karol ◽  
Michael Schär ◽  
Michael Hottiger ◽  
...  
Keyword(s):  
Rotator Cuff ◽  
Mouse Model ◽  
Rotator Cuff Tear ◽  
Fatty Infiltration ◽  
Knock Out ◽  
Cuff Tear ◽  
Parp 1

scholarly journals mTOR regulates fatty infiltration through SREBP-1 and PPARγ after a combined massive rotator cuff tear and suprascapular nerve injury in rats

2012 ◽  
Vol 31 (5) ◽  
pp. 724-730 ◽  
Author(s):  
Sunil K. Joshi ◽  
Xuhui Liu ◽  
Sanjum P. Samagh ◽  
David H. Lovett ◽  
Sue C. Bodine ◽  
...  
Keyword(s):  
Rotator Cuff ◽  
Nerve Injury ◽  
Rotator Cuff Tear ◽  
Fatty Infiltration ◽  
Suprascapular Nerve ◽  
Massive Rotator Cuff Tear ◽  
Cuff Tear

scholarly journals Shoulder Function and Fatty Infiltration on MRI in Older Adults During Rehabilitation for Rotator Cuff Tear

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 960-960
Author(s):  
Derik Davis ◽  
Ranyah Almardawi ◽  
Omer Awan ◽  
Lawrence Lo ◽  
Sagheer Ahmed ◽  
...  
Keyword(s):  
Older Adults ◽  
Rotator Cuff ◽  
Rotator Cuff Tear ◽  
Fatty Infiltration ◽  
Shoulder Function ◽  
Control Cohort ◽  
Cuff Tear ◽  
Supraspinatus Tear ◽  
Cohort Groups ◽  
Over Time

Abstract Rotator cuff tear is highly prevalent in older adults, with supraspinatus tendon tear (STT) the most common. Shoulder rehabilitation is a major treatment strategy, but supraspinatus-muscle-fatty infiltration (FI) and shoulder function in older adults with rotator cuff tear primarily managed by physical therapy (PT) is inadequately documented. We tested the hypothesis that older adults receiving usual-care PT when stratified by supraspinatus tear-status differ in supraspinatus FI [by quantitative Dixon fat fraction (FF) and semi-quantitative Goutallier grade (GG) on MRI] and shoulder function [by the American Shoulder and Elbow Surgeons score (ASES-score)] over time. Longitudinal cohort study (pilot): adults 60-85 years, PT-cohort (n=15) and control-cohort (n=25). Participants completed both shoulder MRI and ASES survey at baseline and follow-up visits. Kruskal-Wallis test compared within cohort among 3 groups: no tear (no-STT), partial-thickness tear (pt-STT), full-thickness tear (ft-STT). Mann-Whitney U test compared equivalent groups between cohorts. Baseline PT-cohort groups differed for GG (p=0.033) [no tear, 0.50±0.50;pt-STT, 1.11±0.22;ft-STT, 1.50±0.50] without difference in age, BMI, comorbidity, or ASES-score. Baseline control-cohort groups differed for FF (p=0.034) [no-tear, 5.77%±1.16%;pt-STT, 7.14%±6.26%;ft-STT, 21.44%±10.44%], without difference in age, BMI, comorbidity, or ASES-score. Baseline no-tear groups for ASES-score (p=0.049) differed between cohorts: PT-cohort (58.87±8.21) versus control-cohort (83.98±21.89). Both cohorts showed no difference in Δ-FF or Δ-GG over time. PT-cohort groups differed for Δ-ASES-score over time (p=0.042)[no-tear, 16.65±4.69;pt-STT, -7.24±0.94;ft-STT, 4.48±3.45], but control-cohort groups did not (p&gt;0.050). Our results suggest differences exist for supraspinatus FI and self-reported shoulder function among older adults receiving PT for rotator cuff tear when stratified by supraspinatus tear-status.

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