title: The microRNA-29 family in cartilage homeostasis and osteoarthritis.
abstract: MicroRNAs have been shown to function in cartilage development and homeostasis, as well as in progression of osteoarthritis. The objective of the current study was to identify microRNAs involved in the onset or early progression of osteoarthritis and characterise their function in chondrocytes. MicroRNA expression in mouse knee joints post-DMM surgery was measured over 7 days. Expression of miR-29b-3p was increased at day 1 and regulated in the opposite direction to its potential targets. In a mouse model of cartilage injury and in end-stage human OA cartilage, the miR-29 family was also regulated. SOX9 repressed expression of miR-29a-3p and miR-29b-3p via the 29a/b1 promoter. TGFβ1 decreased expression of miR-29a, b, and c (3p) in primary chondrocytes, whilst IL-1β increased (but LPS decreased) their expression. The miR-29 family negatively regulated Smad, NFκB, and canonical WNT signalling pathways. Expression profiles revealed regulation of new WNT-related genes. Amongst these, FZD3, FZD5, DVL3, FRAT2, and CK2A2 were validated as direct targets of the miR-29 family. These data identify the miR-29 family as microRNAs acting across development and progression of OA. They are regulated by factors which are important in OA and impact on relevant signalling pathways.
  
  
  
  Expression of the miR-29 family is regulated in cartilage during osteoarthritis. SOX9 represses expression of the miR-29 family in chondrocytes. The miR-29 family is regulated by TGF-β1 and IL-1 in chondrocytes. The miR-29 family negatively regulates Smad, NFκB, and canonical Wnt signalling. Several Wnt-related genes are direct targets of the miR-29 family.
authors.affiliation: Biomedical Research Centre, School of Biological Sciences, Norwich Research Park, University of East Anglia, Norwich, Norfolk, NR4 7TJ, UK.
authors.forename: Linh T T
authors.initials: LT
authors.lastname: Le
authors.affiliation: Biomedical Research Centre, School of Biological Sciences, Norwich Research Park, University of East Anglia, Norwich, Norfolk, NR4 7TJ, UK.
authors.forename: Tracey E
authors.initials: TE
authors.lastname: Swingler
authors.affiliation: Biomedical Research Centre, School of Biological Sciences, Norwich Research Park, University of East Anglia, Norwich, Norfolk, NR4 7TJ, UK.
authors.forename: Natalie
authors.initials: N
authors.lastname: Crowe
authors.affiliation: Department of Cell Signalling, Kennedy Institute of Rheumatology, University of Oxford, Oxfordshire, UK.
authors.forename: Tonia L
authors.initials: TL
authors.lastname: Vincent
authors.affiliation: Musculoskeletal Research Group, Institute of Cellular Medicine, Newcastle University, Newcastle-upon-Tyne, UK.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Barter
authors.affiliation: Institute of Orthopaedics, Norfolk and Norwich University Hospital, Norfolk, UK.
authors.forename: Simon T
authors.initials: ST
authors.lastname: Donell
authors.affiliation: Center for Molecular Medicine, University of Connecticut Health Center, Farmington, CT, USA.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Delany
authors.affiliation: Biomedical Research Centre, School of Biological Sciences, Norwich Research Park, University of East Anglia, Norwich, Norfolk, NR4 7TJ, UK.
authors.forename: Tamas
authors.initials: T
authors.lastname: Dalmay
authors.affiliation: Musculoskeletal Research Group, Institute of Cellular Medicine, Newcastle University, Newcastle-upon-Tyne, UK.
authors.forename: David A
authors.initials: DA
authors.lastname: Young
authors.affiliation: Biomedical Research Centre, School of Biological Sciences, Norwich Research Park, University of East Anglia, Norwich, Norfolk, NR4 7TJ, UK. i.clark@uea.ac.uk.
authors.forename: Ian M
authors.initials: IM
authors.lastname: Clark
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002358:Cartilage, Articular / Q000378:metabolism* / Q000473:pathology; D019902:Chondrocytes / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation; D006706:Homeostasis; D006801:Humans; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D005810:Multigene Family; D010003:Osteoarthritis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D055758:SOX9 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: C532045:MIRN29a microRNA, human; D035683:MicroRNAs; D055758:SOX9 Transcription Factor; D053773:Transforming Growth Factor beta1
keywords: Chondrocyte; MicroRNA; Osteoarthritis; Sry-related box 9; Wnt pathway