The calcium‐sensing receptor and 25‐hydroxyvitamin D–1α‐hydroxylase interact to modulate skeletal growth and bone turnover |
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Authors: | Christian Richard Rujuan Huo Rana Samadfam Isabel Bolivar Dengshun Miao Edward M Brown Geoffrey N Hendy David Goltzman |
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Institution: | 1. Calcium Research Laboratory, Department of Medicine, McGill University, Montreal, Quebec, Canada;2. Department of Human Anatomy, Nanjing Medical University, Nanjing, People's Republic of China;3. Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA |
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Abstract: | We examined parathyroid and skeletal function in 3‐month‐old mice expressing the null mutation for 25‐hydroxyvitamin D–1α‐hydroxylase 1α(OH)ase?/?] and in mice expressing the null mutation for both the 1α(OH)ase and the calcium‐sensing receptor Casr?/?1α(OH)ase?/?] genes. On a normal diet, all mice were hypocalcemic, with markedly increased parathyroid hormone (PTH), increased trabecular bone volume, increased osteoblast activity, poorly mineralized bone, enlarged and distorted cartilaginous growth plates, and marked growth retardation, especially in the compound mutants. Osteoclast numbers were reduced in the Casr?/?1α(OH)ase?/? mice. On a high‐lactose, high‐calcium, high‐phosphorus “rescue” diet, serum calcium and PTH were normal in the 1α(OH)ase?/? mice but increased in the Casr?/?1α(OH)ase?/? mice with reduced serum phosphorus. Growth plate architecture and mineralization were improved in both mutants, but linear growth of the double mutants remained abnormal. Mineralization of bone improved in all mice, but osteoblast activity and trabecular bone volume remained elevated in the Casr?/?1α(OH)ase?/? mice. These studies support a role for calcium‐stimulated maturation of the cartilaginous growth plate and mineralization of the growth plate and bone and calcium‐stimulated CaSR‐mediated effects on bone resorption. PTH‐mediated bone resorption may require calcium‐stimulated CaSR‐mediated enhancement of osteoclastic activity. © 2010 American Society for Bone and Mineral Research. © 2010 American Society for Bone and Mineral Research |
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Keywords: | calcium‐sensing receptor vitamin D parathyroid hormone action osteomalacia bone resorption |
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