A potential role of chondroitin sulfate on bone in osteoarthritis: inhibition of prostaglandin E-2 and matrix metalloproteinases synthesis in interleukin-1 beta- stimulated osteoblasts

作者：Pecchi E; Priam S; Mladenovic Z; Gosset M; Saurel A S; Aguilar L; Berenbaum F^*; Jacques C

来源：Osteoarthritis and Cartilage, 2012, 20(2): 127-135.

DOI：10.1016/j.joca.2011.12.002

• Chondroitin sulfate
• Osteoblasts
• MMPs
• PGE2
• Osteoarthritis

Objectives: To determine the effect of chondroitin sulfate (CS) on inflammatory mediators and proteolytic enzymes induced by interleukin-1 beta (IL-1 beta) and related to cartilage catabolism in murine osteoblasts.
Design: Osteoblasts were obtained by enzymatic digestion of calvaria from Swiss mice and cultured for 3 weeks as a primary culture. Cells were then stimulated with IL-1 beta (1 or 10 ng/ml). CS-treated osteoblasts were incubated with 100 mu g/ml of CS during the last week of culture w/o IL-1 beta for the last 24 h. Expressions of cyclooxygenase-2 (COX-2), microsomal prostaglandin E synthase-1 (mPGES-1), 15-PG dehydrogenase (15-PGDH), matrix metalloproteinases-3 and -13 (MMP-3 and -13), osteoprotegerin (OPG) and receptor activator of nuclear factor-kappa B ligand (RANKL) were determined by real-time polymerase chain reaction (PCR). PGE(2), MMP-3 and MMP-13 release were assessed in the medium by enzyme-linked immunosorbent assay or western-blotting.
Results: IL-1 beta increased COX-2, mPGES-1, MMP-3, MMP-13, RANKL expressions, decreased 15-PGDH expression, and increased PGE2, MMP-3 and MMP-13 release. Interestingly, 7 days of CS treatment significantly counteracted IL-1 beta-induced expression of COX-2 (-62%, P <0.001), mPGES-1 (-63%, P < 0.001), MMP-3 (-39%, P = 0.08), MMP-13 (-60%, P < 0.001) and RANKL (-84%, P<0.001). Accordingly, IL-1 beta-induced PGE(2), MMP-3 and MMP-13 releases were inhibited by 86% (P<0.001), 58%(P <0.001) and 38% (P<0.01) respectively.
Conclusions: In conclusion, our data demonstrate that, in an inflammatory context, CS inhibits the production of PGE(2) and MMPs. Since CS has previously been shown to counteract the production of these mediators in chondrocytes, we speculate that the beneficial effect of CS in Osteoarthritis (OA) could not only be due to its action on cartilage but also on subchondral bone.

• 出版日期2012-2