| 20200973 |
Richard C, Huo R, Samadfam R, Bolivar I, Miao D, Brown EM, Hendy GN, Goltzman D: The calcium sensing receptor and 25-hydroxyvitamin D-1alpha-hydroxylase interact to modulate skeletal growth and bone turnover. J Bone Miner Res. 2010 Feb 8.
We examined parathyroid and skeletal function in 3-month old mice expressing the null mutation for the 25-hydroxyvitamin D-1alpha-hydroxylase (1alpha (OH) ase (-/-)), and in mice expressing the null mutation for both the 1alpha (OH) ase and the calcium sensing receptor (Casr) (Casr (-/-) 1alpha (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 (-/-) 1alpha (OH) ase (-/-) mice. On a high lactose, high calcium, high phosphorus "rescue" diet, serum calcium, and PTH were normal in the 1alpha (OH) ase (-/-) mice, but increased in the Casr (-/-) 1alpha (OH) ase (-/-) mice with reduced serum phosphorus. Growth plate architecture and mineralization was improved in both mutants, but linear growth of the double mutants remained abnormal. Mineralization of bone improved in all mice, however osteoblast activity and trabecular bone volume remained elevated in the Casr (-/-) 1alpha (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 in calcium-stimulated CaSR-mediated effects on bone resorption. PTH-mediated bone resorption may require calcium-stimulated, CaSR-mediated enhancement of osteoclastic activity. (c) 2010 American Society for Bone and Mineral Research. |
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