Location and gene-specific effects of methylprednisolone acetate on mitigating IL1β-induced inflammation in mature ovine explant knee tissue

Abstract

Objective and design: To determine the ability of methylprednisolone acetate (MPA) to influence interleukin 1β (IL1β)-induced gene expression in ovine knee joint tissues.

Material or subjects: Ovine articular cartilage, synovium, and infrapatellar fat pad (IPFP) explants.

Treatment: Explants were treated with 10^-3 M or 10^-4 M MPA.

Methods: Explant treatment groups: (1) control (DMEM); (2) inflammation (IL1β); (3) IL1β + 10^-3 M MPA; or (4) IL1β + 10^-4 M 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 C _T method.

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.

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