부산대학교 도서관

1,25-Dihydroxyvitamin [D.sub.3] (1,25(OH)2[D.sub.3])-mediated intestinal calcium (Ca) absorption supplies Ca for proper bone mineralization during growth. We tested whether vitamin D receptor [(VDR)-mediated 1,25(OH).sub.2][D.sub.3] signaling is critical for adult Ca absorption and bone by using mice with inducible Vdr gene knockout in the whole intestine (villin-[CreER.sup.T2+/-] * [Vdr.sup.f/f], WIK) or in the large intestine (Cdx2-[CreER.sup.T2+/-] *[Vdr.sup.f/f], LIK). At 4-month-old, Vdr alleles were recombined (0.05 mg 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).sub.2][D.sub.3], 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).sub.2][D.sub.3] 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).sub.2][D.sub.3] (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. Key Words: vitamin D, nutrition, transcription factors, intestinal calcium absorption, [micro]CT, genetic animal models Abbreviations: [micro]CT, microcomputed tomography; 1,25[(OH).sub.2][D.sub.3], 1,25-dihydroxyvitamin [D.sub.3]; BMC, bone mineral content; BMD, bone mineral density; BV/TV, bone volume fraction; Ca, calcium; Ct.Ar, cortical bone area; CtAr/Tt.Ar, cortical area fraction; CtTh, cortical bone thickness; Dd, duodenum; IP, intraperitoneal; HVDRR, hereditary vitamin D-resistant rickets; KO, knockout; LIK, Cdx2-[CreER.sup.T2+/]- *[Vdr.sup.f/f]; mRNA, messenger RNA; PBM, peak bone mass; PCo, proximal colon; PCR, polymerase chain reaction; PTH, parathyroid hormone; qPCR, quantitative polymerase chain reaction; ROI, region of interest; RT, real-time; Tb.N, trabecular number; Tb.Sp, trabecular separation; Tb.Th, trabecular thickness; TtAr, total area; VDR, vitamin D receptor; WIK, villin-[CreER.sup.T2+/]- * [Vdr.sup.f/f].
Osteoporosis is a global public health concern characterized by low bone mass and bone structural deterioration, causing bone fragility and increased risk for fracture at multiple bone sites (1). Increasing [...]