Estrogen alone or in combination with parathyroid hormone can decrease vertebral MEF2 and sclerostin expression and increase vertebral bone mass in ovariectomized rats.

Abstract

The study is about the regulatory effects of estrogen and parathyroid hormone (PTH) on sclerostin, a protein that inhibits the Wnt/β-catenin pathway. The results indicate that estrogen may down-regulate sclerostin expression and that estrogen displays synergistic action with PTH. These results provide a new perspective on the relationship between estrogen and bone. To investigate whether estrogen can down-regulate SOST and MEF2 (myocyte enhancer factor 2) expression and whether co-treatment with estrogen and PTH has a stronger effect on suppressing SOST than PTH applied alone in ovariectomized rats. Forty-three-month-old virgin female Sprague-Dawley (SD) rats were ovariectomized and divided into four groups (n = 10). Another ten age-matched rats received sham operations as controls. After allowing 8 weeks for the development of vertebral osteopenia, the rats were administered the drug intervention. For this intervention, the estrogen group was subcutaneously injected with 17β-estradiol at 25 μg/kg body weight, the PTH group was injected with 80 μg/kg synthetic human PTH (1-34), and the co-treatment group was concurrently treated with PTH and estrogen at the above dosage. The OVX group and sham group were treated with vehicle. The drug treatment was conducted for 12 weeks. After the lumbar spine bone mineral density (BMD) was measured, the rats were sacrificed, and the lumbar spine and blood were collected for qPCR, Western blot, immunohistochemistry and other tests. Estrogen can down-regulate MEF2 and sclerostin expression, and co-treatment with estrogen and PTH has a stronger effect on suppressing MEF2 and SOST mRNA than PTH alone. The co-treatment group displayed slightly higher bone mass and biomechanical properties than the PTH group, but the differences were not significant. Estrogen appears to be a regulator of sclerostin, and the effect may involve suppressing MEF2s. Combined treatment with PTH and estrogen is not more beneficial for vertebral bone mass and strength than treatment with PTH alone in ovariectomized rats.