Chondrocyte activation in response to factor(s) produced by a continuous line of lapine synovial fibroblasts

Abstract

We have established a permanent line of lapine synovial fibroblasts called HIG-82. Upon appropriate stimulation, these cells mimicked primary cultures of lapine synovial cells in producing substances which activated primary cultures of lapine articular chondrocytes. Activated chondrocytes secreted prostaglandin E₂ (PGE₂) and latent neutral collagenase, gelatinase, and caseinase, but not acid hydrolases, into their culture media. PGE₂ itself did not activate the chondrocytes. Heating the crude, synovial-conditioned media at 70 °C for 30 min reduced their activating activity by 49.3 ± 20.5% (n = 7). Production of PGE₂ by chondrocytes was maximal during the first day of exposure to synovial conditioned media, whereas the production of neutral proteinases peaked during the second day. All the chondrocyte-stimulating activity was present in a fraction of M_r 10 000–25 000. Unlike the crude conditioned medium, this partially-purified material retained full activity following heating to 70 °C for 30 min. These data indicate that synovial fibroblasts (type B synoviocytes) are a source of chondrocyte activator(s) and that neutral, but not acid, proteinases may be involved in extracellular proteolysis which leads to the resorption of the cartilaginous matrix seen in bioassays of catabolin.