Intestinal Vitamin D Receptor Is Dispensable for Maintaining Adult Bone Mass in Mice with Adequate Calcium Intake

Abstract

1 25-Dihydroxyvitamin D3 (1 25(OH)2D3)-mediated intestinal calcium (Ca) absorption supplies Ca for proper bone mineralization during growth. We tested whether vitamin D receptor (VDR)-mediated 1 25(OH)2D3 signaling is critical for adult Ca absorption and bone by using mice with inducible Vdr gene knockout in the whole intestine (villin-CreERT2+/-a?aVdrf/f WIK) or in the large intestine (Cdx2-CreERT2+/-a?Vdrf/f LIK). At 4-month-old Vdr alleles were recombined (0.05amg tamoxifen/g BW intraperitoneally [i.p.] 5 days) and mice were fed diets with either 0.5% (adequate) or 0.2% (low) Ca. Ca absorption was examined after 2 weeks while serum 1 25(OH)2D3 bone mass and bone microarchitecture were examined after 16 weeks. Intestinal and renal gene expression was measured at both time points (n = 12/genotype/diet/time point). On the 0.5% Ca diet all phenotypes in WIK and LIK mice were similar to the controls. Control mice adapted to the 0.2% low-Ca diet by increasing renal Cyp27b1 mRNA (3-fold) serum 1 25(OH)2D3 level (1.9-fold) and Ca absorption in the duodenum (Dd + 131%) and proximal colon (PCo + 28.9%) which prevented bone loss. In WIK mice low-Ca diet increased serum 1 25(OH)2D3 (4.4-fold) but Ca absorption remained unaltered in the Dd and PCo. Consequently significant bone loss occurred in WIK mice (e.g. cortical thickness Ct.Th -33.7%). LIK mice adapted to the low-Ca diet in the Dd but not the PCo and the effect on bone phenotypes was milder (e.g. Ct.Th -13.1%). Our data suggest intestinal VDR in adult mice prevents bone loss under low Ca intake but is dispensable under adequate calcium intake. ? 2023 The Author(s). Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved.