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

Inflamm Res. 2021 Jan;70(1):99-107. doi: 10.1007/s00011-020-01421-2. Epub 2020 Nov 23.

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.

Keywords: Articular cartilage; Explant cultures; Glucocorticoid; Infrapatellar fat pad; Methylprednisolone acetate; Synovium.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Cartilage, Articular / cytology
  • Cartilage, Articular / drug effects*
  • Cartilage, Articular / metabolism
  • Cell Survival / drug effects
  • Cytokines / genetics
  • Female
  • Gene Expression / drug effects
  • Interleukin-1beta*
  • Knee Joint / cytology
  • Knee Joint / drug effects*
  • Knee Joint / metabolism
  • Matrix Metalloproteinases / genetics*
  • Methylprednisolone Acetate / pharmacology*
  • RNA, Messenger / metabolism
  • Sheep
  • Synovial Membrane / cytology
  • Synovial Membrane / drug effects*
  • Synovial Membrane / metabolism

Substances

  • Anti-Inflammatory Agents
  • Cytokines
  • Interleukin-1beta
  • RNA, Messenger
  • Methylprednisolone Acetate
  • Matrix Metalloproteinases