1. Vdr expression in osteoclast precursors is not critical in bone homeostasis.
- Author
-
Verlinden L, Janssens I, Doms S, Vanhevel J, Carmeliet G, and Verstuyf A
- Subjects
- Animals, Calcium deficiency, Calcium, Dietary, Cells, Cultured, Coculture Techniques, Female, Homeostasis, Macrophages, Peritoneal metabolism, Mice, Transgenic, Osteoblasts metabolism, Receptors, Calcitriol genetics, Bone and Bones metabolism, Osteoclasts metabolism, Receptors, Calcitriol metabolism
- Abstract
The long-recognized role of the vitamin D endocrine system is to maintain stable serum calcium concentrations, which are ensured by a complex interplay between parathyroid gland, kidney, intestine, and bone. However, although VDR is expressed in osteoclastogenic cells, the contribution of VDR-mediated signaling to osteoclast differentiation and activity remains undefined. We therefore deleted Vdr expression efficiently and specifically in myeloid cells by use of M lysozyme-driven Cre expression, which targets granulocytes, monocytes, macrophages and osteoclasts (Vdr
myel- mice). Bone and calcium homeostasis were investigated under basal conditions and in conditions of increased bone remodeling, by feeding Vdrmyel- and Vdrmyel+ (wildtype) mice either a normal (1%) or a low (0.02%) calcium diet from weaning onwards. Vdrmyel- mice developed normally and were normocalcemic at the age of 8 weeks, both at the normal and the low calcium diet. No differences in trabecular or cortical bone mass were observed between Vdrmyel- mice and their wildtype littermates. Dietary calcium restriction resulted in a comparable reduction of trabecular bone mass (40%) and cortical thickness (48%) in Vdrmyel- and Vdrmyel+ mice, pointing to a massive transfer of calcium from the bone to the serum. In agreement with these results, osteoclastic differentiation of hematopoietic cells of Vdrmyel- mice, either induced by M-CSF and RANKL, or cocultured with osteoblasts, occurred as efficiently as osteoclastogenesis from Vdrmyel+ mice. In conclusion, our data do not support a role for osteoclastic Vdr signaling in the control of bone homeostasis., (Copyright © 2019 Elsevier Ltd. All rights reserved.)- Published
- 2019
- Full Text
- View/download PDF