Expression of osteoprotegerin in placenta and its association with preeclampsia

Abstract

Background: Osteoprotegerin (OPG), a key regulatory factor in bone metabolism, was documented also a potential pro-angiogenic factor, which acts an important role in protecting vascular endothelial cells. Since preeclampsia has gradually been employed to be vascular diseases, we speculated that OPG might be associated with preeclampsia. The study was to evaluate the level of OPG protein and mRNA in placenta, and investigate the relationship between OPG and the pathogenesis of preeclampsia.

Methodology/principal findings: Placental specimens from 30 term normal pregnancy, 30 severe preeclampsia and 30 mild cases were studied. The expression and levels of OPGs' protein and mRNA were detected by immunohistochemistry, western blot analysis and real-time quantitative PCR analysis respectively. The expression of OPG protein was found in cytoplasm of placenta cytotrophoblasts and syncytiotrophoblasts in three groups. There were no significant differences of OPG protein between the maternal and fetal side in each group. The OPG protein and mRNA levels in severe preeclampsia were significantly higher than those in mild cases and normal pregnancy. However, there were no markedly differences of the OPG protein and mRNA levels between term delivery and preterm delivery in severe cases. In preeclampsia, the OPG protein and mRNA level was positively correlated with systolic blood pressure and 24 h urinary protein respectively.

Conclusions/significance: OPG protein and mRNA level in placentas of preeclampsia were found abnormal compared with normal pregnancy. In preeclampsia, the OPG protein and mRNA levels were closely related with its important clinical parameters. Taken together, OPG might be closely correlated with the pathogenesis of preeclampsia.

Figure 1. Immunoreactivity for OPG on human placental tissues.

Immunoreactivity for OPG on normal term placentas (A), mild preeclampsia placentas (B), and severe preeclampsia placentas (C). OPG was localized in cytotrophoblast [C] and syncytiotrophoblast [S] cells (×400). Positive control of adipose tissues shows OPG immunostaining (D; ×400); however, negative control of the primary antibody normal term placenta obtained by substituting the primary antibody with phosphate buffer saline (PBS) shows no OPG immunostaining (E; ×400).

Figure 2. Western Blotting analysis result of OPG protein expressions in different groups.

Figure 3. Expressions of OPG protein in different groups (Gray Value).

Figure 4. The OPG mRNA level in human placental tissues.

The OPG mRNA level in severe preeclamptic group was much higher than those of the mild preeclamptic and normal control group.