Abstract
The active form of vitamin D, 1,25(OH)2D, is a crucial regulator of calcium homeostasis, especially through stimulation of intestinal calcium transport. Lack of intestinal vitamin D receptor (VDR) signaling does however not result in hypocalcemia, because the increased 1,25(OH)2D levels stimulate calcium handling in extra-intestinal tissues. Systemic VDR deficiency, on the other hand, results in hypocalcemia because calcium handling is impaired not only in the intestine, but also in kidney and bone. It remains however unclear whether low intestinal VDR activity, as observed during aging, is sufficient for intestinal calcium transport and for mineral and bone homeostasis. To this end, we generated mice that expressed the Vdr exclusively in the gut, but at reduced levels. We found that ~15% of intestinal VDR expression greatly prevented the Vdr null phenotype in young-adult mice, including the severe hypocalcemia. Serum calcium levels were, however, in the low-normal range, which may be due to the suboptimal intestinal calcium absorption, renal calcium loss, insufficient increase in bone resorption and normal calcium incorporation in the bone matrix. In conclusion, our results indicate that low intestinal VDR levels improve intes...Continue Reading
References
Dec 15, 1991·Gene·C PerretM Thomasset
Feb 1, 1990·Endocrinology·R L HorstT A Reinhardt
Aug 1, 1997·Nature Genetics·T YoshizawaS Kato
Oct 28, 1999·Endocrinology·M AmlingM B Demay
Feb 19, 2000·Biochemical and Biophysical Research Communications·F LorgetM Brazier
Nov 1, 2001·Proceedings of the National Academy of Sciences of the United States of America·S J Van CromphautG Carmeliet
Jun 29, 2002·Molecular Endocrinology·Reinhold G ErbenRudi Balling
Mar 31, 2004·Proceedings of the National Academy of Sciences of the United States of America·Melita M DvorakDaniela Riccardi
Jun 18, 2004·Cell Calcium·Melita M Dvorak, Daniela Riccardi
Apr 22, 2005·Human Molecular Genetics·Yingben XueDengshun Miao
Jun 11, 2005·Endocrinology·Sutada LotinunRussell T Turner
Jun 25, 2005·Proceedings of the National Academy of Sciences of the United States of America·Yves SabbaghMarie B Demay
Nov 2, 2006·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·R MentaverriE M Brown
Nov 14, 2006·The Journal of Clinical Investigation·Ritsuko MasuyamaGeert Carmeliet
Nov 18, 2006·Endocrinology·Yurong Song, James C Fleet
Sep 4, 2008·Science Signaling·Wenhan ChangDolores Shoback
Mar 4, 2009·Gastroenterology·Yingben Xue, James C Fleet
Apr 28, 2009·The British Journal of Nutrition·Christian OudshoornEdgar M Colin
Jul 15, 2009·Lancet·William D Fraser
Feb 10, 2010·Cell Metabolism·Jun GuoHenry M Kronenberg
Apr 20, 2010·Bone·L LiebenG Carmeliet
May 27, 2010·Endocrinology·Jun GuoHenry M Kronenberg
Jun 10, 2010·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Mary L BouxseinRalph Müller
Dec 22, 2010·Proceedings of the National Academy of Sciences of the United States of America·Takao HiraiHenry M Kronenberg
Oct 1, 2011·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Melita M Dvorak-EwellDolores M Shoback
Apr 12, 2012·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Ritsuko MasuyamaToshihisa Komori
Apr 24, 2012·The Journal of Clinical Investigation·Liesbet LiebenGeert Carmeliet
Oct 18, 2012·Bone·Liesbet Lieben, Geert Carmeliet
Feb 8, 2013·Endocrinology·Yoko YamamotoYuuki Imai
Citations
Dec 29, 2017·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Atsushi UekawaRitsuko Masuyama
Aug 3, 2019·The Journal of Nutrition·Yujing HuangWeiqun Shu
Sep 25, 2017·Endocrinology·Puneet DhawanSylvia Christakos
Mar 18, 2020·Reviews in Endocrine & Metabolic Disorders·A GiustinaJ P Bilezikian
Dec 1, 2020·The American Journal of Chinese Medicine·Xiao-Li LiYan Zhang
Aug 14, 2021·Nutrition·Aiko Ono-OhmachiRitsuko Masuyama