title: MicroRNAs Associated with Shoulder Tendon Matrisome Disorganization in Glenohumeral Arthritis.
abstract: The extracellular matrix (ECM) provides core support which is essential for the cell and tissue architectural development. The role of ECM in many pathological conditions has been well established and ECM-related abnormalities leading to serious consequences have been identified. Though much has been explored in regards to the role of ECM in soft tissue associated pathologies, very little is known about its role in inflammatory disorders in tendon. In this study, we performed microRNA (miRNA) expression analysis in the long head of the human shoulder biceps tendon to identify key genes whose expression was altered during inflammation in patients with glenohumeral arthritis. We identified differential regulation of matrix metalloproteinases (MMPs) that could be critical in collagen type replacement during tendinopathy. The miRNA profiling showed consistent results between the groups and revealed significant changes in the expression of seven different miRNAs in the inflamed tendons. Interestingly, all of these seven miRNAs were previously reported to have either a direct or indirect role in regulating the ECM organization in other pathological disorders. In addition, these miRNAs were also found to alter the expression levels of MMPs, which are the key matrix degrading enzymes associated with ECM-related abnormalities and pathologies. To our knowledge, this is the first report which identifies specific miRNAs associated with inflammation and the matrix reorganization in the tendons. Furthermore, the findings also support the potential role of these miRNAs in altering the collagen type ratio in the tendons during inflammation which is accompanied with differential expression of MMPs.
authors.affiliation: Department of Clinical & Translational Science, Creighton University School of Medicine, Omaha, Nebraska, United States of America.
authors.forename: Finosh G
authors.initials: FG
authors.lastname: Thankam
authors.affiliation: Department of Clinical & Translational Science, Creighton University School of Medicine, Omaha, Nebraska, United States of America.
authors.forename: Chandra S
authors.initials: CS
authors.lastname: Boosani
authors.affiliation: Department of Orthopedic Surgery, Creighton University School of Medicine, Omaha, Nebraska, United States of America.
authors.forename: Matthew F
authors.initials: MF
authors.lastname: Dilisio
authors.affiliation: Department of Pathology, Creighton University School of Medicine, Omaha, Nebraska, United States of America.
authors.forename: Nicholas E
authors.initials: NE
authors.lastname: Dietz
authors.affiliation: Department of Clinical & Translational Science, Creighton University School of Medicine, Omaha, Nebraska, United States of America.
authors.forename: Devendra K
authors.identifier: http://orcid.org/0000-0001-5445-0013
authors.initials: DK
authors.lastname: Agrawal
mesh_terms: D001168:Arthritis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D003094:Collagen / Q000378:metabolism; D005109:Extracellular Matrix / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016326:Extracellular Matrix Proteins / Q000235:genetics* / Q000378:metabolism*; D020869:Gene Expression Profiling; D056726:Genetic Association Studies; D006801:Humans; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics*; D046228:Microarray Analysis; D012782:Shoulder; D012785:Shoulder Joint / Q000378:metabolism / Q000473:pathology*; D052256:Tendinopathy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D013710:Tendons
chemical_list: D016326:Extracellular Matrix Proteins; D035683:MicroRNAs; D003094:Collagen; D020782:Matrix Metalloproteinases