Osteoarthritic synovial tissue inhibits proteoglycan production in human osteoarthritic cartilage
Establishment and characterisation of a long-term coculture.
Abstract. OBJECTIVE.: Although both cartilage and synovium are affected in osteoarthritis, no in vitro coculture models of human osteoarthritic tissues have been described. The aim of this study is to develop an in vitro model that includes both synovium and cartilage. METHODS.: Cartilage and synovium explants were cultured alone or in coculture for 21 days. Histology, LDH release, matrix metalloproteinase (MMP) activity, glycosaminoglycan (GAG) content, release and synthesis and cytokine production were used to evaluate synovial tissue functionality and its effect on cartilage metabolism. To assess the possibility of intervention in the model system, the effect of triamcinolone was studied. RESULTS.: Throughout the entire culture period, synovial tissue remained viable and produced cytokines. Monocultures of synovial and cartilage explants produced different cytokine subsets. Cytokine subsets in coculture were most similar to those previously described in osteoarthritis synovial fluid. MMP activity was only detectable in synovial explant monoculture and in coculture. Coculture with synovial tissue reduced final GAG content (P< 0.02) via inhibition of GAG production (P< 0.001) rather than through increase of GAG release. Addition of triamcinolone inhibited cytokine production, MMP activity in coculture and synovial tissue and counteracted the inhibition of GAG production induced by coculture. Triamcinolone in cartilage monoculture, however, reduced GAG production. CONCLUSION.: Synovium affects cartilage metabolism by reduction of GAG production. Triamcinolone relieved this inhibition, while being inhibitory when added to cartilage monoculture. These results clearly indicate the importance of tissue coculture, which may be a promising tool for studying osteoarthritis pathophysiology and evaluation of possible interventions.