deletion of pth rescues skeletal abnormalities and high osteopontin levels in klotho？？ mice删除甲状旁腺素救援骨骼畸形和骨桥蛋白水平高克罗索 老鼠.pdfVIP

Deletion of PTH Rescues Skeletal Abnormalities and High Osteopontin Levels in Klotho2/ 2 Mice 1,2 1 1 3 ¨ 4 Quan Yuan , Tadatoshi Sato , Michael Densmore , Hiroaki Saito , Christiane Schuler , 4 1 Reinhold G. Erben , Beate Lanske * 1 Department of Developmental Biology, Harvard School of Dental Medicine, Boston, Massachusetts, United States of America, 2 State Key Laboratory of Oral Diseases, Sichuan University, Chengdu, China, 3 Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Boston, Massachusetts, United States of America, 4 Institute of Physiology, Pathophysiology, and Biophysics, Department of Biomedical Sciences, University of Veterinary Medicine, Vienna, Austria Abstract Maintenance of normal mineral ion homeostasis is crucial for many biological activities, including proper mineralization of the skeleton. Parathyroid hormone (PTH), Klotho, and FGF23 have been shown to act as key regulators of serum calcium and phosphate homeostasis through a complex feedback mechanism. The phenotypes of Fgf232/ 2 and Klotho2/ 2 (Kl2/ 2) mice are very similar and include hypercalcemia, hyperphosphatemia, hypervitaminosis D, suppressed PTH levels, and severe osteomalacia/osteoidosis. We recently reported that complete ablation of PTH from Fgf232/ 2 mice ameliorated the phenotype in Fgf232/ 2 2/ 2 2/ 2 /PTH mice by suppressing serum vitamin D and calcium levels. The severe osteomalacia in Fgf23 mice, however, persisted, suggesting that a different mechanism is responsible for this min