Kristen I Barton1,2,3, May Chung4, Cyril B Frank5,4,6,7, Nigel G Shrive5,7, David A Hart4,7,8. 1. Orthopaedic Surgery, Schulich School of Dentistry and Medicine, London Health Sciences Centre, Western University, 1151 Richmond St, London, ON, N6A 5C1, Canada. kbarto@uwo.ca. 2. McCaig Institute for Bone and Joint Health, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada. kbarto@uwo.ca. 3. Faculty of Kinesiology, University of Calgary, Calgary, AB, Canada. kbarto@uwo.ca. 4. McCaig Institute for Bone and Joint Health, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada. 5. Orthopaedic Surgery, Schulich School of Dentistry and Medicine, London Health Sciences Centre, Western University, 1151 Richmond St, London, ON, N6A 5C1, Canada. 6. Faculty of Kinesiology, University of Calgary, Calgary, AB, Canada. 7. Schulich School of Engineering, University of Calgary, Calgary, AB, Canada. 8. Bone and Joint Strategic Clinical Network, Alberta Health Services, Edmonton, AB, Canada.
Abstract
OBJECTIVE AND DESIGN: This study aimed at evaluating the effect of methylprednisolone (MPA) on messenger ribonucleic acid (mRNA) expression levels in immature ovine knee joint tissue explants following interleukin (IL)1β induction and to assess responsiveness of the explants. MATERIAL OR SUBJECTS: Explants were harvested from the articular cartilage, synovium, and infrapatellar fat pad (IPFP) from immature female sheep. TREATMENT: Methylprednisolone. METHODS: The samples were allocated into six groups: (1) control, (2) MPA (10-3 M), (3) MPA (10-4 M), (4) IL1β, (5) IL1β + 10-3 M MPA, or (6) IL1β + 10-4 M MPA. mRNA expression levels for molecules relevant to inflammation, cartilage degradation/anabolism, activation of innate immunity, and adipose tissue/hormones were quantified. Fold changes with MPA treatment were compared via the comparative CT method. RESULTS: Methylprednisolone treatment significantly suppressed MMPs consistently across the cartilage (MMP1, MMP3, and MMP13), synovium (MMP1 and MMP3), and IPFP (MMP13) (all p < 0.05). Other genes that were less consistently suppressed include endogenous IL1β (cartilage) and IL6 (IPFP) (all p < 0.05), and others not affected either by IL-1 exposure or subsequent MPA include TGFβ1, TLR4, and adipose-related molecules. CONCLUSIONS: Methylprednisolone significantly mitigated IL1β induced mRNA expression for MMPs in the immature cartilage, synovium, and IPFP, but the extent of the responsiveness was tissue-, location-, and gene-specific.
OBJECTIVE AND DESIGN: This study aimed at evaluating the effect of methylprednisolone (MPA) on messenger ribonucleic acid (mRNA) expression levels in immature ovine knee joint tissue explants following interleukin (IL)1β induction and to assess responsiveness of the explants. MATERIAL OR SUBJECTS: Explants were harvested from the articular cartilage, synovium, and infrapatellar fat pad (IPFP) from immature female sheep. TREATMENT: Methylprednisolone. METHODS: The samples were allocated into six groups: (1) control, (2) MPA (10-3 M), (3) MPA (10-4 M), (4) IL1β, (5) IL1β + 10-3 M MPA, or (6) IL1β + 10-4 M MPA. mRNA expression levels for molecules relevant to inflammation, cartilage degradation/anabolism, activation of innate immunity, and adipose tissue/hormones were quantified. Fold changes with MPA treatment were compared via the comparative CT method. RESULTS:Methylprednisolone treatment significantly suppressed MMPs consistently across the cartilage (MMP1, MMP3, and MMP13), synovium (MMP1 and MMP3), and IPFP (MMP13) (all p < 0.05). Other genes that were less consistently suppressed include endogenous IL1β (cartilage) and IL6 (IPFP) (all p < 0.05), and others not affected either by IL-1 exposure or subsequent MPA include TGFβ1, TLR4, and adipose-related molecules. CONCLUSIONS:Methylprednisolone significantly mitigated IL1β induced mRNA expression for MMPs in the immature cartilage, synovium, and IPFP, but the extent of the responsiveness was tissue-, location-, and gene-specific.
Authors: I Tchetverikov; L S Lohmander; N Verzijl; T W J Huizinga; J M TeKoppele; R Hanemaaijer; J DeGroot Journal: Ann Rheum Dis Date: 2005-05 Impact factor: 19.103
Authors: Suzi H Madsen; Kim V Andreassen; Søren T Christensen; Morten A Karsdal; Francis M Sverdrup; Anne-Christine Bay-Jensen; Kim Henriksen Journal: Steroids Date: 2011-08-10 Impact factor: 2.668