Details

Autor(en) / Beteiligte

• van Geffen, E.W.
• van Caam, A.P.M.
• Schreurs, W.
• van de Loo, F.A.
• van Lent, P.L.E.M.
• Koenders, M.I.
• Thudium, C.S.
• Bay-Jensen, A.C.
• Blaney Davidson, E.N.
• van der Kraan, P.M.

Titel

IL-37 diminishes proteoglycan loss in human OA cartilage: donor-specific link between IL-37 and MMP-3

Ist Teil von

• Osteoarthritis and cartilage, 2019-01, Vol.27 (1), p.148-157

Ort / Verlag

England: Elsevier Ltd

Erscheinungsjahr

2019

Quelle

ScienceDirect

Beschreibungen/Notizen

• A hallmark of osteoarthritis (OA) is degradation of articular cartilage proteoglycans. In isolated human OA chondrocytes, the anti-inflammatory cytokine Interleukin-37 (IL-37) lowers the expression of the proteolytic MMP and ADAMTS enzymes, which mediate this degradation. Therefore, we investigated if IL-37 protects against proteoglycan loss in freshly obtained human OA explants. Human OA cartilage explants were incubated with IL-37. Release of sulphated proteoglycans (sGAGs) was measured with the dimethylmethylene-blue assay. Production and degradation of newly synthesized proteoglycans was measured using 35S-sulphate. Proteoglycan and proteolytic enzyme expression were analyzed by qPCR and Western Blot. Proteolytic activity was determined by measuring MMP- and ADAMTS-generated aggrecan neo-epitopes with ELISA and by using MMP-3-, MMP-13- or ADAMTS-5-inhibitors. Over time, a linear release of sGAGs from OA cartilage was measured. IL-37 reduced this release by 87 μg/ml (24%) 95%CI [21.04–141.4]. IL-37 did not affect 35S-sulphate incorporation or proteoglycan gene expression. In contrast, IL-37 reduced loss of 35S-sulphate labeled GAGs and reduced MMP-3 protein expression, indicating that IL-37 inhibits proteoglycan degradation. Remarkably, we observed two groups of patients; one group in which MMP-3-inhibition lowered sGAG release, and one group in which ADAMTS5-inhibition had this effect. Remarkably, IL-37 was only functional in the group of patients that responded to MMP-3-inhibition. We identified a relationship between IL-37 and reduced sGAG loss in OA cartilage. Most likely, this effect is mediated by inhibition of MMP-3 expression. These results suggest that IL-37 could be applied as therapy in a subgroup of OA patients, in which cartilage degradation is mediated by MMP-3.