Functional estrogen receptors in adult articular cartilage - Estrogen replacement therapy increases chondrocyte synthesis of proteoglycans and insulin-like growth factor binding protein 2

Objective. Epidemiologic studies suggest a protective effect of estrogen re placement therapy (ERT) against the development of knee and hip osteoarthri tis, but a potential mechanism for this effect is not known. The present st udy was done to determine if functional estrogen receptors (ERs) are presen t in adult articular cartilage and to determine if ERT in vivo affects the production of insulin-like growth factor binding proteins (IGPBPs). Methods. Reverse transcription-polymerase chain reaction, immunoblotting, a nd immunohistochemistry were used to measure messenger RNA (mRNA) and prote in for ERs in adult monkey articular cartilage. Cultured chondrocytes trans fected with a reporter construct containing the estrogen response element ( ERE/luciferase) were stimulated with estrogen in vitro to determine functio nal activity of the ERs. IGFBP production was measured by ligand and immuno blotting of conditioned media of cells cultured from control and estrogen-t reated surgically menopausal monkeys. Proteoglycan (PG) synthesis was estim ated by measurement of (SO4)-S-35 incorporation. Results. ER alpha and ER beta mRNA were present in adult monkey articular c artilage, and ER protein was demonstrated by immunoblotting and immunohisto chemistry. Estrogen treatment in vitro of cells transfected with the ERE/lu ciferase construct resulted in a 2.87-fold increase (P = 0.0163) in reporte r production over that of untreated cells. Compared with untreated controls , IGFBP-2 production was significantly increased (P < 0.008) in conditioned media of chondrocytes cultured from monkeys that had received ERT in vivo. Increased IGFBP-2 in these cultures was associated with a 1.41-fold increa se (P = 0.02) in the level of sulfate incorporation. Conclusion. Transcriptionally functional ER are present in adult articular cartilage, and ERT increases the production of IGFBP-2 and the synthesis of PGs by chondrocytes from surgically menopausal monkeys. These results indi cate that estrogen can have a direct effect on adult articular cartilage.