The production of PGE2 by chondrocytes and its regulation by vitamin D metabolites was examined in this study as a function of cell maturation. Costochondral chondrocytes, derived from the resting zone and growth zone cartilage, were grown in culture to fourth passage. At confluence, they were exposed to 10-8-10-11M 1,25-(OH)2D36 or to 10-7-10-10M 24,25-(OH)2D3 for either five minutes or 3,6,12, or 24 hours. Indomethacin (10-7M) was added to one-half of the cultures to block the production of PGE2. The amount of PGE2 released into the media was determined by radioimmunoassay. Both growth zone and resting zone cells produced PGE2 in a time-dependent manner; PGE2 concentration was greater in the resting zone cell cultures. 1,25-(OH)2D3 stimulated PGE2 production by growth zone cells in a dose-dependent manner, significant at 10-8-10-10M. This effect was observed at 3 hours and remained elevated during the 24 hours of culture. 1,25-(OH)2D3 had no effect on PGE2 production by resting zone cells. However, 24,25-(OH)2D3 (10-7-10-8M) inhibited PGE2 production from 3-24 hours. No effect was noted when 24,25-(OH)2D3 was added to growth zone cells. Indomethacin reduced PGE2 production to baseline values in all groups examined. The results indicate that chondrocytes in culture produce PGE2. Production is regulated by vitamin D3 metabolites and is cell maturation-dependent. The correlation between hormone-dependent PGE2 production and phospholipase A2 activity suggests that the effects of 1,25-(OH)2D3 and 24,25-(OH)2D3 on chondrocytes may be mediated, in part, by changes in phospholipase A2 activity, arachidonic acid release, and PGE2 production. PGE2 may then act as a second messenger in a paracrine or autocrine manner.
- 1,25-(OH)D-24,25-(OH) D
- Chondrocyte culture
- Vitamin D
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism