PMID- 23072922
OWN - NLM
STAT- MEDLINE
DCOM- 20130926
LR  - 20211203
IS  - 1873-2763 (Electronic)
IS  - 1873-2763 (Linking)
VI  - 54
IP  - 2
DP  - 2013 Jun
TI  - Vitamin D signaling in osteocytes: effects on bone and mineral homeostasis.
PG  - 237-43
LID - S8756-3282(12)01315-4 [pii]
LID - 10.1016/j.bone.2012.10.007 [doi]
AB  - The active form of vitamin D [1,25(OH)2D] is an important regulator of calcium 
      and bone homeostasis, as evidenced by the consequences of 1,25(OH)2D inactivity 
      in man and mice, which include hypocalcemia, hypophosphatemia, secondary 
      hyperparathyroidism and bone abnormalities. The recent generation of 
      tissue-specific (intestine, osteoblast/osteocyte, chondrocyte) vitamin D receptor 
      (Vdr) null mice has provided mechanistic insight in the cell-specific actions of 
      1,25(OH)2D and their contribution to the integrative physiology of VDR signaling 
      that controls bone and mineral metabolism. These studies have demonstrated that 
      even with normal dietary calcium intake, 1,25(OH)2D is crucial to maintain normal 
      calcium and bone homeostasis and accomplishes this primarily through stimulation 
      of intestinal calcium transport. When, moreover, insufficient calcium is acquired 
      from the diet (severe dietary calcium restriction, lack of intestinal VDR 
      activity), 1,25(OH)2D levels will increase and will directly act on osteoblasts 
      and osteocytes to enhance bone resorption and to suppress bone matrix 
      mineralization. Although this system is essential to maintain normal calcium 
      levels in blood during a negative calcium balance, the consequences for bone are 
      disastrous and generate an increased fracture risk. These findings evidently 
      demonstrate that preservation of serum calcium levels has priority over skeletal 
      integrity. Since vitamin D supplementation is an essential part of 
      anti-osteoporotic therapy, mechanistic insight in vitamin D actions is required 
      to define the optimal therapeutic regimen, taking into account the amount of 
      dietary calcium supply, in order to maximize the targeted outcome and to avoid 
      side-effects. We will review the current understanding concerning the functions 
      of osteoblastic/osteocytic VDR signaling which not only include the regulation of 
      bone metabolism, but also comprise the control of calcium and phosphate 
      homeostasis via fibroblast growth factor (FGF) 23 secretion and the maintenance 
      of the hematopoeitic stem cell (HSC) niche, with special focus on the 
      experimental data obtained from systemic and osteoblast/osteocyte-specific Vdr 
      null mice.
CI  - Copyright (c) 2012 Elsevier Inc. All rights reserved.
FAU - Lieben, Liesbet
AU  - Lieben L
AD  - Clinical and Experimental Endocrinology, KU Leuven, Leuven, Belgium.
FAU - Carmeliet, Geert
AU  - Carmeliet G
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20121013
PL  - United States
TA  - Bone
JT  - Bone
JID - 8504048
RN  - 0 (FGF23 protein, human)
RN  - 0 (Fgf23 protein, mouse)
RN  - 0 (Minerals)
RN  - 1406-16-2 (Vitamin D)
RN  - 7Q7P4S7RRE (Fibroblast Growth Factor-23)
SB  - IM
MH  - Animals
MH  - Bone and Bones/*metabolism
MH  - Fibroblast Growth Factor-23
MH  - *Homeostasis
MH  - Humans
MH  - Minerals/*metabolism
MH  - Osteocytes/*metabolism
MH  - *Signal Transduction
MH  - Vitamin D/*metabolism
EDAT- 2012/10/18 06:00
MHDA- 2013/09/27 06:00
CRDT- 2012/10/18 06:00
PHST- 2012/08/16 00:00 [received]
PHST- 2012/10/02 00:00 [revised]
PHST- 2012/10/04 00:00 [accepted]
PHST- 2012/10/18 06:00 [entrez]
PHST- 2012/10/18 06:00 [pubmed]
PHST- 2013/09/27 06:00 [medline]
AID - S8756-3282(12)01315-4 [pii]
AID - 10.1016/j.bone.2012.10.007 [doi]
PST - ppublish
SO  - Bone. 2013 Jun;54(2):237-43. doi: 10.1016/j.bone.2012.10.007. Epub 2012 Oct 13.