The calcium-sensing receptor and 25-hydroxyvitamin D–1α-hydroxylase interact to modulate skeletal growth and bone turnover

Abstract

We examined parathyroid and skeletal function in 3-month-old mice expressing the null mutation for 25-hydroxyvitamin D-1a-hydroxylase [1a(OH)ase À/À ] and in mice expressing the null mutation for both the 1a(OH)ase and the calcium-sensing receptor [Casr À/À 1a(OH)ase À/À ] 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 À/À 1a(OH)ase À/À mice. On a high-lactose, high-calcium, high-phosphorus ''rescue'' diet, serum calcium and PTH were normal in the 1a(OH)ase À/À mice but increased in the Casr À/À 1a(OH)ase À/À 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 À/À 1a(OH)ase À/À 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. ß

Osteoblast Menin Regulates Bone Mass in Vivo

“…Calcein (Sigma; C-0875) was dissolved in buffer (0.15 M NaCl, 2% NaHCO 3 ) and injected twice intraperitoneally (25 g/g body weight) at 9 and 2 days before the mice were killed (29). Bones were harvested and embedded in plastic as described above.…”

The Calcium-Sensing Receptor and the Parathyroid: Past, Present, Future

“…Recently developed mouse models, however, suggest that this is so (Chang et al, 2008; Richard et al, 2010; reviews: Goltzman and Hendy, 2015; Santa Maria et al, 2016). An authoritative database of CaSR mutations and their links to human disease is maintained at: http://www.casrdb.mcgill.ca/.…”

The Calcium-Sensing Receptor and 25-Hydroxyvitamin D–1α-Hydroxylase Interact to Modulate Skeletal Growth and Bone Turnover

“…A reader of the JBMR informed the editors about concern regarding a possible duplicate image in Fig. in Richard and colleagues . In consultation with the Committee on Publication Ethics (COPE) guidelines, the editors sought an explanation from the authors for this possible panel duplication.…”

“…In Richard and colleagues, the authors acknowledge an error made in presenting the images in Fig. B , with an image and a partial enlargement appearing in two panels, but were unable to ascertain the source of the duplication.…”