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

Arthritis Rheum. 2012 Jun;64(6):1799-808. doi: 10.1002/art.34338. Epub 2011 Dec 14.


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-1-expressing 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-1-positive 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-1-positive cells were macrophages. In RA and OA, the density of PlGF-1-positive cells correlated positively with the density of macrophages and the density of type IV collagen-positive vessels. The supernatant concentration of (3) H-DHEA after conversion from (3) H-DHEAS and the density of aromatase-positive cells were positively correlated with the density of PlGF-1-positive cells only in OA. Low DHEA concentrations (≤10(-9) M) had stimulatory effects on PlGF-1 when compared to serum concentrations (10(-8) M to 10(-7) M) 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aromatase / metabolism*
  • Arthritis, Rheumatoid / metabolism*
  • Dehydroepiandrosterone / metabolism*
  • Dehydroepiandrosterone Sulfate / metabolism*
  • Female
  • Humans
  • Knee Joint / metabolism
  • Macrophages / metabolism
  • Male
  • Middle Aged
  • Neovascularization, Pathologic / metabolism*
  • Osteoarthritis, Knee / metabolism*
  • Placenta Growth Factor
  • Pregnancy Proteins / metabolism*
  • Synovial Fluid / metabolism
  • Synovial Membrane / metabolism*
  • Vascular Endothelial Growth Factor A / metabolism


  • PGF protein, human
  • Pregnancy Proteins
  • Vascular Endothelial Growth Factor A
  • Placenta Growth Factor
  • Dehydroepiandrosterone
  • Dehydroepiandrosterone Sulfate
  • Aromatase