Paper 81: Gene Expression of Procollagens and Matrix Metalloproteases in Rotator Cuff Tear

2021 ◽  
Vol 49 (2) ◽  
pp. 332-339
Author(s):  
Hideyuki Shirasawa ◽  
Noboru Matsumura ◽  
Masaki Yoda ◽  
Kazumasa Okubo ◽  
Masayuki Shimoda ◽  
...  

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.


2021 ◽  
pp. 036354652110545
Author(s):  
Michael R. Davies ◽  
Hannah Chi ◽  
Gurbani Kaur ◽  
Mengyao Liu ◽  
C. Benjamin Ma ◽  
...  

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.


2018 ◽  
Vol 2018 ◽  
pp. 1-18 ◽  
Author(s):  
Yong-Soo Lee ◽  
Ja-Yeon Kim ◽  
Hyo-Nam Kim ◽  
Dhong-Won Lee ◽  
Seok Won Chung

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.


2017 ◽  
Vol 475 (7) ◽  
pp. 1904-1910 ◽  
Author(s):  
Jorge H. Assunção ◽  
Alexandre L. Godoy-Santos ◽  
Maria Cristina L. G. dos Santos ◽  
Eduardo A. Malavolta ◽  
Mauro E. C. Gracitelli ◽  
...  

2019 ◽  
Vol 39 (10) ◽  
Author(s):  
Kaisong Miao ◽  
Lifeng Jiang ◽  
Xindie Zhou ◽  
Lidong Wu ◽  
Yong Huang ◽  
...  

Abstract An association of Matrix Metalloproteinases-1/3 (MMP-1/3) rs1799750/rs3025058 polymorphism with increased risk of rotator cuff tear (RCT) has been reported in a Brazilian population. However, this significant association has not been confirmed in the Chinese population. Genotyping was conducted by polymerase chain reaction (PCR)-restriction fragment length polymorphism and direct sequencing. Our results demonstrated that individuals with the TT genotype had a significantly higher risk of RCT compared with those with the CC genotype. The increased risk of RCT progression was associated with the 2G allele of the rs1799750 polymorphism. No significant association was observed for genotypic and allelic frequencies of the rs3025058 polymorphism. A significant association of the MMP-1 rs1799750 polymorphism was observed with smokers, drinkers and people aged ≥60 years and non-diabetic people. Additionally, the MMP-1 rs1799750 polymorphism was associated with pre-operative stiffness in RCT patients. In conclusion, a significant correlation was identified between the MMP-1 rs1799750 polymorphism and RCT. The MMP-1 rs1799750 polymorphism might be considered as a biomarker of genetically high-risk RCT, helping to clarify the mechanism of RCT.


2021 ◽  
Vol 30 (1) ◽  
pp. 200-215
Author(s):  
Johanna J. Mousley ◽  
Leaha-Marie Hill-Buxton ◽  
Stephen D. Gill ◽  
Sean L. McGee ◽  
Richard S. Page

PLoS ONE ◽  
2015 ◽  
Vol 10 (3) ◽  
pp. e0118821 ◽  
Author(s):  
Mariana Ferreira Leal ◽  
Paulo Santoro Belangero ◽  
Eduardo Antônio Figueiredo ◽  
Carina Cohen ◽  
Leonor Casilla Loyola ◽  
...  

2018 ◽  
Vol 1 ◽  
pp. 9
Author(s):  
Harshad Arvind Vanjare ◽  
Jyoti Panwar

Objective The objective of the study was to assess the accuracy of ultrasound examination for the diagnosis of rotator cuff tear and tendinosis performed by a short experienced operator, compared to magnetic resonance imaging (MRI) results. Method A total of 70 subjects suspected to have rotator cuff tear or tendinosis and planned for shoulder MRI were included in the study. Shoulder ultrasound was performed either before or after the MRI scan on the same day. Ultrasound operator had a short experience in performing an ultrasound of the shoulder. Ultrasound findings were correlated to MRI findings. Results Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for the diagnosis of tendinosis were 58%, 84%, 63%, 80%, and 75%, respectively, and it was 68%, 91%, 73%, 88%, and 85%, respectively, for the diagnosis of rotator cuff tear. Conclusions Sensitivity for diagnosing rotator cuff tear or tendinosis was moderate but had a higher negative predictive value. Thus, the ultrasound operator with a short experience in performing shoulder ultrasound had moderate sensitivity in diagnosing tendinosis or tears; however, could exclude them with confidence.


Sign in / Sign up

Export Citation Format

Share Document