Modulation of fibroblast-mediated cartilage degradation by articular chondrocytes in rheumatoid arthritis

Objective, To determine the role of chondrocytes and factors released from chondrocytes in cartilage destruction by fibroblast-like synoviocytes (FLS) derived from patients with rheumatoid arthritis (RA). Methods. RA FLS from 2 patients were implanted into SCID mice, together wit h fresh articular cartilage or with cartilage that had been stored for 24 h ours at 4 degreesC or at 37 degreesC, The invasion of the same RA FLS into the fresh and stored cartilage was compared histologically using a semiquan titative scoring system. In addition, we investigated whether protein synth esis in chondrocytes affects the invasion of RA FLS in vitro. A 3-dimension al cartilage-like matrix formed by cultured chondrocytes was labeled with S -35. After formation of the cartilage-like matrix, protein synthesis was bl ocked with cycloheximide. The invasion of RA FLS from 6 patients into cyclo heximide-treated and untreated matrix was assessed by measuring the release d radioactivity in coculture with and without interleukin-1 beta (IL-1 beta ) and tumor necrosis factor alpha (TNF alpha). Results. The SCID mouse experiments showed a significant invasion of RA FLS into the cartilage (overall mean score 3.2) but revealed significant diffe rences when the invasion of the same RA FLS into fresh and stored cartilage was compared. RA FLS that were implanted with fresh articular cartilage sh owed a significantly higher invasiveness than those implanted with pieces o f cartilage that had been stored for 24 hours (overall mean score 2.3), Sto rage at 37 degreesC and 4 degreesC resulted in the same reduction of invasi on (35% and 37%, respectively). In the in vitro experiments, RA FLS rapidly destroyed the cartilage-like matrix. Blocking of chondrocyte protein biosy nthesis significantly decreased the invasion of RA FLS, as shown by a decre ased release of radioactivity. Addition of IL-1 beta, but not TNF alpha, to the cocultures partially restored the invasiveness of RA FLS, Conclusion. These data underline the value of the SCID mouse in vivo model of rheumatoid cartilage destruction and demonstrate that chondrocytes contr ibute significantly to the degradation of cartilage by releasing factors th at stimulate RA FLS. Among those, IL-1 beta -mediated mechanisms might be o f particular importance.