Assessment of the Skeletal Phenotype of Aged Vitamin D Receptor (VDR) Knockout Mice: Is VDR Required for Healthy Bone? (#476)
The global VDR deletion mouse model (VDRKO) has previously been shown to demonstrate features typical of vitamin D-dependent type II rickets. However, when mice are fed a diet containing high levels of calcium (2%) and phosphorus (1.25%), hypocalcemia and secondary hyperparathyroidism are prevented, restoring bone mineralization in young mice. While it has been generally accepted that adequate calcium and phosphorus is all that is required for bone health, little assessment has been performed of the bone forming osteoblasts nor osteocytes in terms of gene expression profiles and cell populations. To investigate the role of rescue diet and VDR on skeletal health, weanling VDRKO and WT mice were fed a rescue diet containing 2% calcium, 1.25% phosphorus and 20% lactose until 23 weeks of age. At time of death, femora were collected for structural, cellular and molecular investigations. Serum calcium levels were comparable between WT and VDRKO mice at time of death. Messenger RNA levels for osteocalcin and E11, markers of osteoblasts and osteocytes, were comparable between VDRKO and WT mice. Consistent with this, cortical bone osteocyte-lacunae numbers and lacunae size were comparable between WT and VDRKO mice. However, preliminary data indicate a 50% reduction in the vitamin D-responsive RANKL mRNA levels in VDRKO mice suggesting impaired signaling for osteoclastogenesis necessary for bone resorption. Evaluation of VDRKO trabecular and cortical bone volume is required to establish whether VDRKO maintained on 2% calcium and 1.25% phosphorus have increase bone mineral volume relative to WT mice due to reduced bone resorption rather than an increase in osteoblastic formation.