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127. THE CONCISE GUIDE TO PHARMACOLOGY 2015/16: Overview

Author

Alexander, Stephen PH, Kelly, Eamonn, Marrion, Neil, Peters, John A, Benson, Helen E, Faccenda, Elena, Pawson, Adam J, Sharman, Joanna L, Southan, Christopher, Buneman, Peter O, Catterall, William A, Cidlowski, John A, Davenport, Anthony P, Fabbro, Doriano, Fan, Grace, McGrath, John C, Spedding, Michael, Davies, Jamie A, Aldrich, R, Attali, B, Bäck, M l, Barnes, N M, Bathgate, R, Beart, P M, Becirovic, E, Biel, M, Birdsall, N J, Boison, D, Bräuner-Osborne, H, Bröer, S, Bryant, C, Burnstock, G, Burris, T, Cain, D, Calo, G, Chan, S L, Chandy, K G, Chiang, N, Christakos, S, Christopoulos, A, Chun, J J, Chung, J-J, Clapham, D E, Connor, M A, Coons, L, Cox, H M, Dautzenberg, F M, Dent, G, Douglas, S D, Dubocovich, M L, Edwards, D P, Farndale, R, Fong, T M, Forrest, D, Fowler, C J, Fuller, P, Gainetdinov, R R, Gershengorn, M A, Goldin, A, Goldstein, S AN, Grimm, S L, Grissmer, S, Gundlach, A L, Hagenbuch, B, Hammond, J R, Hancox, J C, Hartig, S, Hauger, R L, Hay, D L, Hébert, T, Hollenberg, A N, Holliday, N D, Hoyer, D, Ijzerman, A P, Inui, K I, Ishii, S, Jacobson, K A, Jan, L Y, Jarvis, G E, Jensen, R, Jetten, A, Jockers, R, Kaczmarek, L K, Kanai, Y, Kang, H S, Karnik, S, Kerr, I D, Korach, K S, Lange, C A, Larhammar, D, Leeb-Lundberg, F, Leurs, R, Lolait, S J, Macewan, D, Maguire, J J, May, J M, Mazella, J, Mcardle, C A, Mcdonnell, D P, Michel, M C, Miller, L J, Mitolo, V, Monie, T, Monk, P N, Mouillac, B, Murphy, P M, Nahon, J-L, Nerbonne, J, Nichols, C G, Norel, X, Oakley, R, Offermanns, S, Palmer, L G, Panaro, M A, Perez-Reyes, E, Pertwee, R G, Pike, J W, Pin, J P, Pintor, S, Plant, L D, Poyner, D R, Prossnitz, E R, Pyne, S, Ren, D, Richer, J K, Rondard, P, Ross, R A, Sackin, H, Safi, R, Sanguinetti, M C, Sartorius, C A, Segaloff, D L, Sladek, F M, Stewart, G, Stoddart, L A, Striessnig, J, Summers, R J, Takeda, Y, Tetel, M, Toll, L, Trimmer, J S, Tsai, M-J, Tsai, S Y, Tucker, S, Usdin, T B, Vilargada, J-P, Vore, M, Ward, D T, Waxman, S G, Webb, P, Wei, A D, Weigel, N, Willars, G B, Winrow, C, Wong, S S, Wulff, H, Ye, R D, Young, M, and Zajac, J-M

Published
2015
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146. Normocalcemia is maintained in mice under conditions of calcium malabsorption by vitamin D-induced inhibition of bone mineralization

Author

Lieben, Liesbet, Masuyama, Ritsuko, Torrekens, Sophie, Van Looveren, Riet, Schrooten, Jan, Baatsen, Pieter, Lafage-Proust, Marie-Helene, Dresselaers, Tom, Feng, Jian Q., Bonewald, Lynda F., Meyer, Mark B., Pike, J. Wesley, Bouillon, Roger, and Carmeliet, Geert

Subjects
Calcium metabolism -- Research, Alfacalcidol -- Research, Calcifediol -- Research, Vitamin D -- Research, Calcification -- Research, Fractures -- Research, Osteopenia -- Research, Health care industry
Abstract

Serum calcium levels are tightly controlled by an integrated hormone-controlled system that involves active vitamin D [1,25[(OH).sub.2]D], which can elicit calcium mobilization from bone when intestinal calcium absorption is decreased. The skeletal adaptations, however, are still poorly characterized. To gain insight into these issues, we analyzed the consequences of specific vitamin D receptor (Vdr) inactivation in the intestine and in mature osteoblasts on calcium and bone homeostasis. We report here that decreased intestinal calcium absorption in intestine-specific Vdr knockout mice resulted in severely reduced skeletal calcium levels so as to ensure normal levels of calcium in the serum. Furthermore, increased 1,25[(OH).sub.2]D levels not only stimulated bone turnover, leading to osteopenia, but also suppressed bone matrix mineralization. This resulted in extensive hyperosteoidosis, also surrounding the osteocytes, and hypomineralization of the entire bone cortex, which may have contributed to the increase in bone fractures. Mechanistically, osteoblastic VDR signaling suppressed calcium incorporation in bone by directly stimulating the transcription of genes encoding mineralization inhibitors. Ablation of skeletal Vdr signaling precluded this calcium transfer from bone to serum, leading to better preservation of bone mass and mineralization. These findings indicate that in mice, maintaining normocalcemia has priority over skeletal integrity, and that to minimize skeletal calcium storage, 1,25[(OH).sub.2]D not only increases calcium release from bone, but also inhibits calcium incorporation in bone., Introduction Ionized serum calcium levels are critical for the correct functioning of multiple vital cellular processes. Accordingly, the regulation of calcium homeostasis is directed at maintaining serum calcium levels within [...]

Published
2012
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