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High intestinal vitamin D receptor level increases molecular markers for intestinal calcium absorption but not bone mineral density in mice
Author(s) -
Schoch Ryan D,
Fleet James C
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.217.5
Subject(s) - calcitriol receptor , endocrinology , medicine , weanling , osteoporosis , bone mineral , calcium , vitamin d and neurology , absorption (acoustics) , calcium metabolism , chemistry , biology , materials science , composite material
1,25‐dihydroxyvitamin D 3 (1,25D) activates the intestinal vitamin D receptor (VDR) to increase calcium (Ca) absorption. VDR level falls with age and resistance to the action of 1,25D reduces the efficiency of intestinal Ca absorption. Additionally, aging is associated with reduced bone mass and increased fracture risk. We examined whether intestine‐specific transgenic over‐expression of human VDR (HV2) increases the response to 1,25D in mice, and whether these adaptations are sufficient to protect bone under conditions of dietary Ca restriction. Weanling, male HV2 and wild type (WT) mice were fed one of four AIN93G diets containing 0.125, 0.25, 0.5, or 1.0 % Ca until 3‐mo of age. Ca restriction increased duodenal TRPV6 and calbindinD 9k mRNA in both groups, but their levels were significantly higher in HV2 mice, suggesting that increasing intestinal VDR level directly augments Ca absorption. In kidney, both genotypes responded to Ca restriction by increasing CYP27B1, indicating adaption to increase 1,25D levels; in HV2 mice, this adaptation was significantly stronger. Despite the effects of HV2 on intestine and kidney, neither total femoral bone mineral density, cortical bone, nor cancellous bone were different between genotypes. Collectively, these data suggest that although Ca absorption may be increased with high intestinal VDR level, the absorbed Ca does not reach bone and is likely eliminated through the renal filtrate. Supported by NIH award DK54111. Grant Funding Source : NIH