Expression of Renal Vitamin D and Phosphatonin-Related Genes in a Sheep Model of Osteoporosis

Abstract

Osteoporosis is a significant public health issue around the world, with post-menopausal osteoporosis due to estrogen deficiency resulting in approximately ¾ of cases. In this study, 18 aged Merino ewes were ovariectomized, and 10 were controls. Three of the ovariectomized ewes were treated weekly with 400 mg of methylprednisolone for 5 months and three were treated weekly for 2 months, followed by a 3-month recovery period. At 2 months, five control animals and six ovariectomized animals were euthanized. At 5 months, all the remaining ewes were euthanized. Kidney samples were collected postmortem for qPCR analysis of <i>NPT1</i>, <i>PTH1R</i>, <i>NPT2a</i>, <i>NPT2c</i>, <i>Klotho</i>, <i>FGFR1IIIc</i>, <i>VDR</i>, <i>CYP24A1</i>, <i>CYP27B1</i>, <i>TRPV5</i>, <i>TRPV6</i>, <i>CalD9k</i>, <i>CalD28k</i>, <i>PMCA</i> and <i>NCX1.</i> Ovariectomized sheep had significantly greater <i>VDR</i> expression compared with other groups. Ovariectomized sheep treated with glucocorticoids for 2 months followed by euthanasia at 5 months showed significant differences in <i>TRPV5</i>, <i>CYP24A1</i> and <i>klotho</i> gene expression compared to other groups. Differences in <i>klotho</i> expression were most marked after adjustment for repeated measures (<i>p</i> = 0.1). <i>Klotho</i> is known as the “anti-aging” hormone and is involved in calcium and phosphorus metabolism. <i>Klotho</i> may be involved in the recovery of bone mineral density in ovariectomized sheep treated with glucocorticoids for 2 months followed by euthanasia at 5 months. Further research on the role of <i>klotho</i> is recommended.