Cartilage inflammation and degeneration is enhanced by pro-inflammatory (M1) macrophages in vitro, but not inhibited directly by anti-inflammatory (M2) macrophages

Objective: Macrophages play a crucial role in the progression of osteoarthritis (OA). Their phenotype may range from pro-inflammatory to anti-inflammatory. The aim of this study was to evaluate the direct effects of macrophage subtypes on cartilage by culturing macrophage conditioned medium (MCM) on human articular cartilage. Design: Human OA cartilage explants were cultured with MCM of pro-inflammatory M(IFN gamma+TNF alpha), or anti-inflammatory M(IL-4) or M(IL-10) human monocyte-derived macrophages. To assess effects of antiinflammatory macrophages, the cartilage was cultured with a combination of MCM phenotypes as well as pre-stimulated with IFN gamma+TNF alpha cartilage before culture with MCM. The reactions of the explants were assessed by gene expression, nitric oxide (NO) production and release of glycosaminoglycans (GAGS). Results: M(IFN gamma+TNF alpha) MCM affected OA cartilage by upregulation of IL1B (Interleukin 1 beta), IL6, MMP13 (Matrix Metalloproteinase-13) and ADAMTS5 (A Disintegrin And Metalloproteinase with Thrombospondin Motifs-5), while inhibiting ACAN (aggrecan) and COL2A1 (collagen type II). M(IL-10) upregulated IL1B and Suppressor of cytokine signaling 1 (SOCS1). NO production and GAG release by the cartilage was increased when cultured with M(IFN gamma+TNF alpha) MCM. M(IL-4) and M(IL-10) did not inhibit the effects of M(IFN gamma+TNF alpha) MCM of neither phenotype affected IFN gamma+TNF alpha pre-stimulated cartilage, in which an inflammatory gene response was deliberately induced. Conclusion: M(IFN gamma+TNF alpha) macrophages have a prominent direct effect on OA cartilage, while M(IL-4) and M(IL-10) do not inhibit the effects of M(IFN gamma+TNF alpha), or IFN gamma+TNF alpha induced inflammation of the cartilage. Therapies aiming at inhibiting cartilage degeneration may take this into account by directing suppression of pro-inflammatory macrophages or stimulation of anti-inflammatory macrophages. (C) 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.