Functional estrogen receptors in articular cartilage: Estrogen effects on chondrocytes and characterization of estrogen receptors in human monocyte-derived macrophages

Epidemiological studies suggest that estrogen replacement therapy (ERT) is protective against the development of both osteoarthritis and atherosclerosis. The focus of this work is the interaction of estrogen with cells intimately associated with each of these pathological processes. Studies were conducted to determine if functional estrogen receptors (ER) are present in adult articular cartilage and to determine if ERT effects in vivo may be mediated by insulin-like growth factor binding proteins (IGFBPs). mRNA for ERα and ERβ was present in adult monkey articular cartilage and ER protein was demonstrated by immunoblotting and immunohistochemistry. Estrogen treatment of chondrocytes transfected with an ERE/Luciferase construct resulted in a significant increase in reporter production (2.87-fold above control, p < 0.02) indicating a functional ER. In primary chondrocytes cultured from monkeys receiving ERT versus no treatment, IGFBP-2 production was increased significantly (p < 0.008). ERT was associated with a significant increase in proteoglycan synthesis in these cells (1.41-fold above control, p < 0.02). These results indicate that estrogen has direct effects on adult articular cartilage and may be a key to how ERT is beneficial to joint metabolism.; Studies directed towards a mechanism for estrogen protection in atherosclerosis focused on human monocyte derived macrophages (HMDM), cells that accumulate in atherosclerotic lesions. Cells were isolated from peripheral blood of male and female donors, separated by Isolymph gradient and differential adherence, then cultured up to 14 days. ERα RT-PCR product was undetectable in initial cultures (day 0), but was expressed from day 5 through 14. ERβ was detected only at day 0, and data suggested this was due to contaminating lymphocytes. These expression patterns were neither gender specific nor regulated by estrogen. ERα expression was approximately 20% that of ovary, but greater than cultured arterial smooth muscle cells. Day 7 HMDM had distinct nuclear ERα staining and bound estrogen, but to a lesser extent than MCF-7 cells. These studies demonstrate that HMDM are a potential target for estrogen and as such may be involved in estrogen-mediated protection against early events in atherosclerosis.