title: Location and gene-specific effects of methylprednisolone acetate on mitigating IL1β-induced inflammation in mature ovine explant knee tissue.
abstract: OBJECTIVE
  To determine the ability of methylprednisolone acetate (MPA) to influence interleukin 1β (IL1β)-induced gene expression in ovine knee joint tissues.
  
  
  METHODS
  Ovine articular cartilage, synovium, and infrapatellar fat pad (IPFP) explants.
  
  
  METHODS
  Explants were treated with 10-3M or 10-4M MPA.
  
  
  METHODS
  Explant treatment groups: (1) control (DMEM); (2) inflammation (IL1β); (3) IL1β + 10-3M MPA; or (4) IL1β + 10-4M MPA. Cell viability was assessed pre- and post-treatment. Expression of mRNA levels for inflammatory, degradative, anabolic, innate immunity, and adipose-related molecules was quantified via qPCR, and analyzed via the comparative CTmethod.
  
  
  RESULTS
  Except for IL8 in a subset of cartilage locations, matrix metalloproteinases (MMPs) were the only genes consistently affected by MPA. MPA mitigated IL1β-induced MMP3 expression levels in all regions of the articular cartilage, and in the synovium and IPFP, while MMP1 mRNA expression levels were significantly decreased with MPA after IL1β in the tibial plateau and synovium, but paradoxical increases in the IPFP. MMP13 mRNA expression levels exhibited significant decreases with MPA after IL1β in the femoral condyles, tibial plateau, synovium, and IPFP.
  
  
  CONCLUSIONS
  MPA treatment suppressed IL1β-induced mRNA levels for MMPs in articular cartilage, synovium, and IPFP and was found to be tissue-, location-, and gene-specific.
authors.affiliation: McCaig Institute for Bone and Joint Health, Cumming School of Medicine, Health Sciences Centre, University of Calgary, 3330 Hospital Drive NW, Calgary, AB, T2N 4N1, Canada.
authors.forename: Kristen I
authors.initials: KI
authors.lastname: Barton
authors.affiliation: McCaig Institute for Bone and Joint Health, Cumming School of Medicine, Health Sciences Centre, University of Calgary, 3330 Hospital Drive NW, Calgary, AB, T2N 4N1, Canada.
authors.forename: Bryan J
authors.initials: BJ
authors.lastname: Heard
authors.affiliation: McCaig Institute for Bone and Joint Health, Cumming School of Medicine, Health Sciences Centre, University of Calgary, 3330 Hospital Drive NW, Calgary, AB, T2N 4N1, Canada.
authors.forename: May
authors.initials: M
authors.lastname: Chung
authors.affiliation: McCaig Institute for Bone and Joint Health, Cumming School of Medicine, Health Sciences Centre, University of Calgary, 3330 Hospital Drive NW, Calgary, AB, T2N 4N1, Canada.|Schulich School of Engineering, University of Calgary, Calgary, AB, Canada.
authors.forename: Johnathan L
authors.initials: JL
authors.lastname: Sevick
authors.affiliation: McCaig Institute for Bone and Joint Health, Cumming School of Medicine, Health Sciences Centre, University of Calgary, 3330 Hospital Drive NW, Calgary, AB, T2N 4N1, Canada.|Section of Orthopaedics, Foothills Hospital, University of Calgary, Calgary, AB, Canada.
authors.forename: C Ryan
authors.initials: CR
authors.lastname: Martin
authors.affiliation: McCaig Institute for Bone and Joint Health, Cumming School of Medicine, Health Sciences Centre, University of Calgary, 3330 Hospital Drive NW, Calgary, AB, T2N 4N1, Canada.
authors.forename: Yamini
authors.initials: Y
authors.lastname: Achari
authors.forename: Cyril B
authors.initials: CB
authors.lastname: Frank
authors.affiliation: McCaig Institute for Bone and Joint Health, Cumming School of Medicine, Health Sciences Centre, University of Calgary, 3330 Hospital Drive NW, Calgary, AB, T2N 4N1, Canada.|Schulich School of Engineering, University of Calgary, Calgary, AB, Canada.
authors.forename: Nigel G
authors.initials: NG
authors.lastname: Shrive
authors.affiliation: McCaig Institute for Bone and Joint Health, Cumming School of Medicine, Health Sciences Centre, University of Calgary, 3330 Hospital Drive NW, Calgary, AB, T2N 4N1, Canada. hartd@ucalgary.ca.
authors.forename: David A
authors.initials: DA
authors.lastname: Hart
mesh_terms: D052242:Adiponectin / Q000235:genetics; D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D002358:Cartilage, Articular / Q000187:drug effects* / Q000378:metabolism; D016207:Cytokines / Q000235:genetics*; D005260:Female; D007249:Inflammation / Q000378:metabolism; D007719:Knee Joint / Q000187:drug effects / Q000378:metabolism; D020738:Leptin / Q000235:genetics; D020782:Matrix Metalloproteinases / Q000235:genetics; D008775:Methylprednisolone / Q000031:analogs & derivatives* / Q000494:pharmacology; D000077555:Methylprednisolone Acetate; D054409:Nicotinamide Phosphoribosyltransferase / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism*; D012756:Sheep; D013583:Synovial Membrane / Q000187:drug effects* / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000235:genetics
chemical_list: D052242:Adiponectin; D016207:Cytokines; D020738:Leptin; D012333:RNA, Messenger; D051197:Toll-Like Receptor 4; D000077555:Methylprednisolone Acetate; D054409:Nicotinamide Phosphoribosyltransferase; D020782:Matrix Metalloproteinases; D008775:Methylprednisolone
keywords: Articular cartilage; Explant; Glucocorticoid; Infrapatellar fat pad; Methylprednisolone acetate; Synovium