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

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 NPT1 , PTH1R , NPT2a , NPT2c , Klotho , FGFR1IIIc , VDR , CYP24A1 , CYP27B1 , TRPV5 , TRPV6 , CalD9k , CalD28k , PMCA and NCX1. Ovariectomized sheep had significantly greater VDR expression compared with other groups. Ovariectomized sheep treated with glucocorticoids for 2 months followed by euthanasia at 5 months showed significant differences in TRPV5 , CYP24A1 and klotho gene expression compared to other groups. Differences in klotho expression were most marked after adjustment for repeated measures ( p = 0.1). Klotho is known as the "anti-aging" hormone and is involved in calcium and phosphorus metabolism. Klotho 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 klotho is recommended.