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Methylprednisolone acetate mitigates IL1β induced changes in matrix metalloproteinase gene expression in skeletally immature ovine explant knee tissues

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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.

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Acknowledgments

This work was funded by the Canadian Institutes of Health Research (CBF, NGS, DAH), The Arthritis Society (CBF, NGS, DAH), Alberta Innovates Health Solutions (KIB, CBF, NGS, DAH), Vanier Canada Graduate Scholarships (KIB), and the Cumming School of Medicine at the University of Calgary (KIB).

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Authors and Affiliations

  1. Orthopaedic Surgery, Schulich School of Dentistry and Medicine, London Health Sciences Centre, Western University, 1151 Richmond St, London, ON, N6A 5C1, Canada

    Kristen I. Barton, Cyril B. Frank & Nigel G. Shrive

  2. McCaig Institute for Bone and Joint Health, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada

    Kristen I. Barton, May Chung, Cyril B. Frank & David A. Hart

  3. Faculty of Kinesiology, University of Calgary, Calgary, AB, Canada

    Kristen I. Barton & Cyril B. Frank

  4. Schulich School of Engineering, University of Calgary, Calgary, AB, Canada

    Cyril B. Frank, Nigel G. Shrive & David A. Hart

  5. Bone and Joint Strategic Clinical Network, Alberta Health Services, Edmonton, AB, Canada

    David A. Hart

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  1. Kristen I. Barton
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  2. May Chung
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  4. Nigel G. Shrive
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  5. David A. Hart
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Contributions

KIB conducted the experimental design, sample collection, data processing, data analysis, and manuscript writing. MC helped in the sample collection, data processing, and data analysis. CBF, NGS and DAH provided their support in experimental design, data analysis, acquired project funding, and manuscript editing.

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Correspondence to Kristen I. Barton.

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The authors have received no financial support that may be perceived as a conflict of interest or have any other relationships which could be perceived as conflicts of interest.

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Responsible Editor: John Di Battista.

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Cyril B. Frank: Deceased.

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Barton, K.I., Chung, M., Frank, C.B. et al. Methylprednisolone acetate mitigates IL1β induced changes in matrix metalloproteinase gene expression in skeletally immature ovine explant knee tissues. Inflamm. Res. 70, 99–107 (2021). https://doi.org/10.1007/s00011-020-01421-2

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  • DOI: https://doi.org/10.1007/s00011-020-01421-2

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