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MicroRNA Profiling Reveals Distinct Signatures in Degenerative Rotator Cuff Pathologies.

ABSTRACT: MicroRNAs (miRNAs) have emerged as key regulators orchestrating a wide range of inflammatory and fibrotic diseases. However, the role of miRNAs in degenerative shoulder joint disorders is poorly understood. The aim of this explorative case-control study was to identify pathology-related, circulating miRNAs in patients with chronic rotator cuff tendinopathy and degenerative rotator cuff tears (RCT). In 2017, 15 patients were prospectively enrolled and assigned to three groups based on the diagnosed pathology: (i) no shoulder pathology, (ii) chronic rotator cuff tendinopathy, and (iii) degenerative RCTs. In total, 14 patients were included. Venous blood samples ("liquid biopsies") were collected from each patient and serum levels of 187 miRNAs were determined. Subsequently, the change in expression of nine candidate miRNAs was verified in tendon biopsy samples, collected from patients who underwent arthroscopic shoulder surgery between 2015 and 2018. Overall, we identified several miRNAs to be progressively deregulated in sera from patients with either chronic rotator cuff tendinopathy or degenerative RCTs. Importantly, for the several of these miRNAs candidates repression was also evident in tendon biopsies harvested from patients who were treated for a supraspinatus tendon tear. As similar expression profiles were determined for tendon samples, the newly identified systemic miRNA signature has potential as novel diagnostic or prognostic biomarkers for degenerative rotator cuff pathologies. © 2019 The Authors. Journal of Orthopaedic Research^® published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society. Inc. J Orthop Res 38:202-211, 2020.

SUBMITTER: Plachel F

PROVIDER: S-EPMC6973295 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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MicroRNA Profiling Reveals Distinct Signatures in Degenerative Rotator Cuff Pathologies.

Plachel Fabian F Heuberer Philipp P Gehwolf Renate R Frank Julia J Tempfer Herbert H Lehner Christine C Weissenbacher Nadja N Wagner Andrea A Weigl Moritz M Moroder Philipp P Hackl Matthias M Traweger Andreas A

Journal of orthopaedic research : official publication of the Orthopaedic Research Society 20191004 1

MicroRNAs (miRNAs) have emerged as key regulators orchestrating a wide range of inflammatory and fibrotic diseases. However, the role of miRNAs in degenerative shoulder joint disorders is poorly understood. The aim of this explorative case-control study was to identify pathology-related, circulating miRNAs in patients with chronic rotator cuff tendinopathy and degenerative rotator cuff tears (RCT). In 2017, 15 patients were prospectively enrolled and assigned to three groups based on the diagnos ...[more]

PMID: 31520478

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Project description:BackgroundThe upper normoglycemic range has been proposed as a risk factor for degenerative rotator cuff tendon tear (RCT), and insulin resistance has been suggested as a risk factor for tendinopathy. However, no research has established their association with degenerative RCT in the general population. This study aimed to determine whether fasting glucose levels and insulin resistance are risk factors for degenerative RCT in the normoglycemic population and identify the risk range for fasting glucose.MethodsThis study included 418 normoglycemic participants from a rural cohort. Participants completed questionnaires, physical exams, blood tests, and MRI evaluations of both shoulders. Insulin resistance was assessed using a triglyceride/high-density-lipoprotein (TG/HDL) ≥ 3.5. Logistic regression analysis was used to determine the association between fasting glucose level, TG/HDL ≥ 3.5, and other factors and degenerative RCT. The study calculated the areas under the receiver operating characteristic curve (AUC) to determine the more appropriate predicting value between the scale and categorical values of fasting glucose levels, and compared the AUCs using the DeLong method.ResultsIn the multivariable analyses, both scale and categorical values of fasting glucose levels, and TG/HDL ≥ 3.5 were significantly associated with degenerative RCT. Fasting glucose levels ≥ 90.5 mg/dL (OR: 3.87, 95% CI: 2.10-7.06) in scale value and 90-99 mg/dL (OR: 4.13, 95% CI: 2.87-8.12) in categorical value were significantly associated with degenerative RCT (P < .001). The AUC of the scale value of fasting glucose levels ≥ 90.5 mg/dL was 0.68. The AUC of the categorical value of fasting glucose levels of 90-99 mg/dL was 0.70. Because of the significantly larger AUC of the categorical value of fasting glucose levels of 90-99 mg/dL, those fasting glucose levels were determined to be independently associated with degenerative RCT (P < .001).ConclusionsHigh fasting glucose levels within the normal range may link to increase insulin resistance and risk of degenerative RCT. Normoglycemic levels of 90-99 mg/dL and insulin resistance may be risk factors for degenerative RCT.Level of evidenceLevel III, prognostic study.

Project description:Myosteatosis is the pathological accumulation of lipid that occurs in conjunction with atrophy and fibrosis following skeletal muscle injury or disease. Little is known about the mechanisms by which lipid accumulates in myosteatosis, but many studies have demonstrated the degree of lipid infiltration negatively correlates with muscle function and regeneration. Our goal was to identify biochemical pathways that lead to muscle dysfunction and lipid accumulation in injured rotator cuff muscles, a model that demonstrates severe myosteatosis. Adult rats were subjected to a massive tear to the rotator cuff musculature. After a period of either 0 (healthy control), 10, 30, or 60 days, muscles were prepared for RNA sequencing, shotgun lipidomics, metabolomics, biochemical measures, electron microscopy, and muscle fiber contractility. Following rotator cuff injury, there was a decrease in muscle fiber specific force production that was lowest at 30d. There was a dramatic time dependent increase in triacylglyceride content. Interestingly, genes related to not only triacylglyceride synthesis, but also lipid oxidation were largely downregulated over time. Using bioinformatics techniques, we identified that biochemical pathways related to mitochondrial dysfunction and reactive oxygen species were considerably increased in muscles with myosteatosis. Long chain acyl-carnitines and L-carnitine, precursors to beta-oxidation, were depleted following rotator cuff tear. Electron micrographs showed injured muscles displayed large lipid droplets within mitochondria at early time points, and an accumulation of peripheral segment mitochondria at all time points. Several markers of oxidative stress were elevated following rotator cuff tear. The results from this study suggest that the accumulation of lipid in myosteatosis is not a result of canonical lipid synthesis, but occurs due to decreased lipid oxidation in mitochondria. A failure in lipid utilization by mitochondria would ultimately cause an accumulation of lipid even in the absence of increased synthesis. Further study will identify whether this process is required for the onset of myosteatosis.

Project description:BackgroundIt has been theorized that degenerative rotator cuff tears most commonly involve the supraspinatus tendon, initiating at the anterior portion of the supraspinatus insertion and propagating posteriorly. The purposes of this study were to determine the most common location of degenerative rotator cuff tears and to examine tear location patterns associated with various tear sizes.MethodsUltrasonograms of 360 shoulders with either a full-thickness rotator cuff tear (272) or a partial-thickness rotator cuff tear (eighty-eight) were obtained to measure the width and length of the tear and the distance from the biceps tendon to the anterior margin of the tear. Tears were grouped on the basis of their size (anteroposterior width) and extent (partial or full-thickness). Each tear was represented numerically as a column of consecutive numbers representing the tear width and distance posterior to the biceps tendon. All tears were pooled to graphically represent the width and location of the tears within groups. Frequency histograms of the pooled data were generated, and the mode was determined for each histogram representing various tear groups.ResultsThe mean age (and standard deviation) of the 233 subjects (360 shoulders) was 64.7 +/- 10.2 years. The mean width and length of the tears were 16.3 +/- 12.1 mm and 17.0 +/- 13.0 mm, respectively. The mean distance from the biceps tendon to the anterior tear margin was 7.8 +/- 5.7 mm (range, 0 to 26 mm). Histograms of the various tear groups invariably showed the location of 15 to 16 mm posterior to the biceps tendon to be the most commonly torn location within the posterior cuff tendons. The histograms of small tears (a width of <10 mm) and partial-thickness tears showed similar distributions of tear locations, indicating that the region approximately 15 mm posterior to the biceps tendon may be where rotator cuff tears most commonly initiate.ConclusionsDegenerative rotator cuff tears most commonly involve a posterior location, near the junction of the supraspinatus and infraspinatus. The patterns of tear location across multiple tear sizes suggest that degenerative cuff tears may initiate in a region 13 to 17 mm posterior to the biceps tendon.

Project description:BackgroundArthroscopic rotator cuff repair (ARCR) is among the most commonly performed orthopaedic procedures. Several factors-including age, sex, and tear severity-have been identified as predictors for outcome after repair. The influence of the tear etiology on functional and structural outcome remains controversial.PurposeTo investigate the influence of tear etiology (degenerative vs traumatic) on functional and structural outcomes in patients with supraspinatus tendon tears.Study designCohort study; Level of evidence, 2.MethodsPatients undergoing ARCR from 19 centers were prospectively enrolled between June 2020 and November 2021. Full-thickness, nonmassive tears involving the supraspinatus tendon were included. Tears were classified as degenerative (chronic shoulder pain, no history of trauma) or traumatic (acute, traumatic onset, no previous shoulder pain). Range of motion, strength, the Subjective Shoulder Value, the Oxford Shoulder Score (OSS), and the Constant-Murley Score (CMS) were assessed before (baseline) and 6 and 12 months after ARCR. The Subjective Shoulder Value and the OSS were also determined at the 24-month follow-up. Repair integrity after 12 months was documented, as well as additional surgeries up to the 24-month follow-up. Tear groups were compared using mixed models adjusted for potential confounding effects.ResultsFrom a cohort of 973 consecutive patients, 421 patients (degenerative tear, n = 230; traumatic tear, n = 191) met the inclusion criteria. The traumatic tear group had lower mean baseline OSS and CMS scores but significantly greater score changes 12 months after ARCR (OSS, 18 [SD, 8]; CMS, 34 [SD,18] vs degenerative: OSS, 15 [SD, 8]; CMS, 22 [SD, 15]) (P < .001) and significantly higher 12-month overall scores (OSS, 44 [SD, 5]; CMS, 79 [SD, 9] vs degenerative: OSS, 42 [SD, 7]; CMS, 76 [SD, 12]) (P≤ .006). At the 24-month follow-up, neither the OSS (degenerative, 44 [SD, 6]; traumatic, 45 [SD, 6]; P = .346) nor the rates of repair failure (degenerative, 14 [6.1%]; traumatic 12 [6.3%]; P = .934) and additional surgeries (7 [3%]; 7 [3.7%]; P = .723) differed between groups.ConclusionPatients with degenerative and traumatic full-thickness supraspinatus tendon tears who had ARCR show satisfactory short-term functional results. Although patients with traumatic tears have lower baseline functional scores, they rehabilitate over time and show comparable clinical results 1 year after ARCR. Similarly, degenerative and traumatic rotator cuff tears show comparable structural outcomes, which suggests that degenerated tendons retain healing potential.

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MicroRNA Profiling Reveals Distinct Signatures in Degenerative Rotator Cuff Pathologies.

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MicroRNA Profiling Reveals Distinct Signatures in Degenerative Rotator Cuff Pathologies.

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