Osteocalcin abnormalities in Hyp mice reflect altered genetic expression and are not due to altered clearance, affinity for mineral, or ambient phosphorus levels

Endocrinology
T O Carpenter, C M Gundberg

Abstract

The Hyp mouse manifests rickets and renal wasting of phosphorus. We previously reported elevated circulating osteocalcin in Hyp mice, and a paradoxical decrease in response to 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]. To investigate these abnormalities further, we characterized in detail the response of circulating osteocalcin to 1,25-(OH)2D3 and compared skeletal osteocalcin in normal and Hyp mice. The affinity of osteocalcin for hydroxyapatite and the protein's clearance were compared in Hyp and normal animals. Finally, the response of osteocalcin messenger RNA (mRNA) to 1,25-(OH)2D3 was examined in normal mice, Hyp mice, and normal mice subjected to dietary phosphorus deprivation. Multiple (n = 3-6) daily doses of 1,25-(OH)2D3 are required to increase serum osteocalcin levels in normal C57 BL/6 mice; the effect is apparent by 6 h and persists for at least 24 h after injection. Single doses of up to 50 ng have no significant effect. In contrast, an approximately 50% decrement in circulating osteocalcin occurs after a single dose of 1,25-(OH)2D3 in Hyp mice. Osteocalcin clearance in Hyp mice appears to be normal. Bone osteocalcin per U calcium or phosphorus is normal in Hyp mice, suggesting that its affinity for hydroxyapatite ...Continue Reading

Citations

Aug 5, 1998·Current Opinion in Nephrology and Hypertension·P S Rowe
Jan 27, 1998·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·A StaalJ P Van Leeuwen
Oct 23, 1997·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·T L ClemensC M Gundberg
Feb 28, 2019·Orphanet Journal of Rare Diseases·Signe Sparre Beck-NielsenOuti Mäkitie
Mar 3, 2007·Pediatrics·Marie B DemayThomas O Carpenter

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