Effects of dehydroepiandrosterone on articular cartilage during the development of osteoarthritis

Objective. To investigate the in vivo effects of dehydroepiandrosterone (DHEA) on knee joints during the development of experimentally induced osteoarthritis (OA). Methods. Twenty-two mature NZW rabbits underwent bilateral anterior cruciate ligament transection (ACLT) and received 0.3-ml intraarticular injections of DHEA (at a concentration of 100 muM in phosphate buffered saline) and control solution in the right and left knees, respectively, beginning 4 weeks after ACLT and continuing once weekly for 5 weeks. All animals were killed 9 weeks after surgery, and the knee joints were assessed by gross morphologic, histologic, histomorphometric, and biochemical methods. Results. Gross morphologic inspection following India ink application showed that the right femoral condyles, which received DHEA, demonstrated less severe cartilage damage than did the contralateral condyles. The thickness, area, and roughness of the DHEA-treated femoral condyles provided evidence of a cartilage-protecting effect of DHEA following ACLT. These results were supported by gene expression analysis. Messenger RNA expression of a proinflammatory cytokine, interleukin-1beta, and catabolic enzymes, matrix metalloproteinases 1 and 3, was reduced in the cartilage of the DHEA-treated knee joints, and expression of tissue inhibitor of metalloproteinase 1 was increased. Conclusion. Results of the present study demonstrate a cartilage-protecting effect of DHEA during the development of OA following ACLT in a rabbit model.