title: Identification of microRNA-181a-5p and microRNA-4454 as mediators of facet cartilage degeneration.
abstract: Osteoarthritis (OA) of spine (facet joints [FJs]) is one of the major causes of severe low back pain and disability worldwide. The degeneration of facet cartilage is a hallmark of FJ OA. However, endogenous mechanisms that initiate degeneration of facet cartilage are unknown, and there are no disease-modifying therapies to stop FJ OA. In this study, we have identified microRNAs (small noncoding RNAs) as mediators of FJ cartilage degeneration. We first established a cohort of patients with varying degrees of facet cartilage degeneration (control group: normal or mild facet cartilage degeneration; FJ OA group: moderate to severe facet cartilage degeneration) and then screened 2,100 miRNAs and identified 2 miRNAs (miR-181a-5p and miR-4454) that were significantly elevated in FJ OA cartilage compared with control facet cartilage. We further explored their role, function, and signaling mechanisms using computational, in vitro functional, and in vivo studies. We specifically indicate that miR-181a-5p and miR-4454 are involved in promoting inflammatory, catabolic, and cell death activity in FJ chondrocytes. This is the first report to our knowledge that identifies miR-181a-5p and miR-4454 as mediators of cartilage degeneration in FJs and potential therapeutic targets for stopping cartilage degeneration.
authors.affiliation: Arthritis Program and.|Division of Genetics and Development, Krembil Research Institute, University Health Network, Toronto, Ontario, Canada.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Nakamura
authors.affiliation: Arthritis Program and.|Spinal Program, Krembil Neuroscience Center, Toronto Western Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Y Raja
authors.initials: YR
authors.lastname: Rampersaud
authors.affiliation: Arthritis Program and.|Division of Genetics and Development, Krembil Research Institute, University Health Network, Toronto, Ontario, Canada.
authors.forename: Anirudh
authors.initials: A
authors.lastname: Sharma
authors.affiliation: Arthritis Program and.|Spinal Program, Krembil Neuroscience Center, Toronto Western Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Lewis
authors.affiliation: Arthritis Program and.|Division of Genetics and Development, Krembil Research Institute, University Health Network, Toronto, Ontario, Canada.
authors.forename: Brian
authors.initials: B
authors.lastname: Wu
authors.affiliation: Arthritis Program and.|Division of Genetics and Development, Krembil Research Institute, University Health Network, Toronto, Ontario, Canada.
authors.forename: Poulami
authors.initials: P
authors.lastname: Datta
authors.affiliation: Arthritis Program and.|Division of Genetics and Development, Krembil Research Institute, University Health Network, Toronto, Ontario, Canada.
authors.forename: Kala
authors.initials: K
authors.lastname: Sundararajan
authors.affiliation: Arthritis Program and.|Division of Genetics and Development, Krembil Research Institute, University Health Network, Toronto, Ontario, Canada.
authors.forename: Helal
authors.initials: H
authors.lastname: Endisha
authors.affiliation: Arthritis Program and.|Division of Genetics and Development, Krembil Research Institute, University Health Network, Toronto, Ontario, Canada.
authors.forename: Evgeny
authors.initials: E
authors.lastname: Rossomacha
authors.affiliation: Arthritis Program and.|Division of Genetics and Development, Krembil Research Institute, University Health Network, Toronto, Ontario, Canada.
authors.forename: Jason S
authors.initials: JS
authors.lastname: Rockel
authors.affiliation: Princess Margaret Cancer Centre, University Health Network and Departments of Medical Biophysics and Computer Science, University of Toronto, Ontario, Canada.
authors.forename: Igor
authors.initials: I
authors.lastname: Jurisica
authors.affiliation: Arthritis Program and.|Division of Genetics and Development, Krembil Research Institute, University Health Network, Toronto, Ontario, Canada.|Department of Surgery and Department of Laboratory Medicine and Pathobiology, University of Toronto, Ontario, Canada.
authors.forename: Mohit
authors.initials: M
authors.lastname: Kapoor
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002358:Cartilage, Articular / Q000473:pathology*; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology*; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D010003:Osteoarthritis / Q000235:genetics* / Q000473:pathology; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction
chemical_list: C000623332:MIRN4454 microRNA, human; C540193:MIrn181 microRNA, human; D035683:MicroRNAs