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MicroRNA Profiling Reveals Distinct Signatures in Degenerative Rotator Cuff Pathologies
Authors:Fabian Plachel  Philipp Heuberer  Renate Gehwolf  Julia Frank  Herbert Tempfer  Christine Lehner  Nadja Weissenbacher  Andrea Wagner  Moritz Weigl  Philipp Moroder  Matthias Hackl  Andreas Traweger
Affiliation:1. Institute of Tendon and Bone Regeneration, Spinal Cord Injury and Tissue Regeneration, Center Salzburg, Paracelsus Medical University, Salzburg, Austria;2. Vienna Shoulder & Sports Clinic, Vienna, Austria;3. Institute of Tendon and Bone Regeneration, Spinal Cord Injury and Tissue Regeneration, Center Salzburg, Paracelsus Medical University, Salzburg, Austria

Austrian Cluster for Tissue Regeneration, Vienna, Austria;4. TAmiRNA GmbH, Vienna, Austria;5. Center for Musculoskeletal Surgery, Campus Virchow, Charité Universitaetsmedizin, Berlin, Germany

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
Keywords:biomarker  circulating microRNA  rotator cuff  tendinopathy  tendon degeneration
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