Relationship between placenta growth factor 1 and vascularization, dehydroepiandrosterone sulfate to dehydroepiandrosterone conversion, or aromatase expression in patients with rheumatoid arthritis and patients with osteoarthritis

Objective Proliferating pannus is in many aspects similar to placental tissue. Both fibroblast-rich tissues have high vascularity, and tissue from patients with rheumatoid arthritis (RA) and patients with osteoarthritis (OA) demonstrates conversion of androgenic prehormones to downstream estrogens. We undertook this study to investigate similarities between proliferating pannus and placental tissue by focusing on angiogenic placenta growth factor 1 (PlGF-1) in patients with OA and patients with RA. Methods We used immunohistochemistry to study the presence of PlGF-1, its synovial distribution, and the PlGF-1expressing synovial cell type. The relationship between PlGF-1 and conversion of the biologically inactive placental prehormone dehydroepiandrosterone sulfate (DHEAS) to the biologically active dehydroepiandrosterone (DHEA) was investigated in mixed synovial cells. The effects of DHEA on PlGF-1 expression were studied by intracellular fluorescence-activated cell sorting analysis. Results PlGF-1positive cells were detected in the lining and sublining areas in patients with RA and patients with OA, and cellular density was similar. Double staining revealed that PlGF-1positive cells were macrophages. In RA and OA, the density of PlGF-1positive cells correlated positively with the density of macrophages and the density of type IV collagenpositive vessels. The supernatant concentration of 3H-DHEA after conversion from 3H-DHEAS and the density of aromatase-positive cells were positively correlated with the density of PlGF-1positive cells only in OA. Low DHEA concentrations (=10-9M) had stimulatory effects on PlGF-1 when compared to serum concentrations (10-8M to 10-7M) in the monocytic cell line THP-1 and in primary mixed synovial cells. Conclusion PlGF-1 functions similarly in inflamed synovium and in the placenta. It is related to vessel formation and, in OA patients, to androgen/estrogen conversion. Evolutionarily conserved functions of PlGF-1 for placental phenomena are obviously also present in synovial inflammation.