title: Genome-wide analysis identifies differential promoter methylation of Leprel2, Foxf1, Mmp25, Igfbp6, and Peg12 in murine tendinopathy.
abstract: We have used a murine Achilles tendinopathy model to investigate whether tissue changes (such as collagen disorganization, chondroid metaplasia, and loss of tensile properties) which are broadly characteristic of human tendinopathies, are accompanied by changes in the expression of chromatin-modifying enzymes and the methylation status of promoter regions of tendon cell DNA. Tendinopathy was induced by two intra-tendinous TGF-β1 injections followed by cage activity or treadmill running for up to 28 days. Activation of DNA methyltransferases occurred at 3 days after the TGF-β1 injections and also at 14 days, but only with treadmill activity. Genome-wide Methyl Mini-Seq™ analysis identified 19 genes with differentially methylated promoters, five of which perform functions with an apparent direct relevance to tendinopathy (Leprel2, Foxf1, Mmp25, Igfbp6, and Peg12). The functions of the genes identified included collagen fiber assembly and pericellular interactions, therefore their perturbation could play a role in the characteristic disorganization of fibers in affected tendons. We postulate that a study of the functional genomics of these genes in animal and human tendon could further delineate the pathogenesis of this multi-factorial complex disease. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:947-955, 2017.
authors: Department of Orthopedic Surgery, Rush University Medical Center, 1611 W. Harrison Street, Suite 201, Chicago, Illinois, 60612.|Department of Bioengineering, University of Illinois at Chicago, 851 S. Morgan Street, 2nd Floor, Chicago, Illinois, 60607.
authors: Katie J
authors: KJ
authors: Trella
authors: Department of Rheumatology/Internal Medicine, Rush University Medical Center, 1611 W. Harrison Street, Suite 510, Chicago, Illinois, 60612.
authors: Jun
authors: J
authors: Li
authors: Formerly Department of Pathobiology, Lerner Research Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, Ohio, 44195.
authors: Eleni
authors: E
authors: Stylianou
authors: Department of Bioengineering, University of Illinois at Chicago, 851 S. Morgan Street, 2nd Floor, Chicago, Illinois, 60607.|Department of Biomedical Engineering and Mechanics, Virginia Tech, Blacksburg, Virginia, 24061.
authors: Vincent M
authors: VM
authors: Wang
authors: Department of Orthopedic Surgery, Rush University Medical Center, 1611 W. Harrison Street, Suite 201, Chicago, Illinois, 60612.
authors: Jonathan M
authors: JM
authors: Frank
authors: Department of Orthopedic Surgery, Rush University Medical Center, 1611 W. Harrison Street, Suite 201, Chicago, Illinois, 60612.
authors: Jorge
authors: J
authors: Galante
authors: Department of Biochemistry, Rush University Medical Center, 1735 W. Harrison Street, 5th Floor, Chicago, Illinois, 60612.
authors: John D
authors: JD
authors: Sandy
authors: Department of Rheumatology/Internal Medicine, Rush University Medical Center, 1611 W. Harrison Street, Suite 510, Chicago, Illinois, 60612.|Department of Biochemistry, Rush University Medical Center, 1735 W. Harrison Street, 5th Floor, Chicago, Illinois, 60612.
authors: Anna
authors: A
authors: Plaas
authors: Department of Orthopedic Surgery, Rush University Medical Center, 1611 W. Harrison Street, Suite 201, Chicago, Illinois, 60612.
authors: Robert
authors: R
authors: Wysocki
mesh_terms: D000125:Achilles Tendon / Q000473:pathology; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics; D019175:DNA Methylation; D004195:Disease Models, Animal; D051858:Forkhead Transcription Factors / Q000235:genetics; D058851:GPI-Linked Proteins / Q000235:genetics; D015870:Gene Expression; D055106:Genome-Wide Association Study; D008297:Male; D053504:Matrix Metalloproteinases, Membrane-Associated / Q000235:genetics; D008810:Mice, Inbred C57BL; D009363:Neoplasm Proteins / Q000235:genetics; D011393:Procollagen-Proline Dioxygenase / Q000235:genetics; D011401:Promoter Regions, Genetic; D052256:Tendinopathy / Q000378:metabolism* / Q000473:pathology
chemical_list: D002352:Carrier Proteins; D051858:Forkhead Transcription Factors; C486293:Foxf1 protein, mouse; D058851:GPI-Linked Proteins; D009363:Neoplasm Proteins; C491814:Peg12 protein, mouse; D011393:Procollagen-Proline Dioxygenase; C586944:LEPREL1 protein, mouse; D053504:Matrix Metalloproteinases, Membrane-Associated; C403928:matrix metalloproteinase 25
keywords: chromatin-modifying enzymes; gene expression; methylome; promoter methylation; tendinopathy