Transcription Role of VDR in regulation of genes involved in osteoporosis
Role of VDR in regulation of genes involved in osteoporosis
Osteoporosis is a common disease affecting the majority of older women and asignificant minority of older men. It is defined as the gradual reduction in bonestrength with advancing age, particularly in post-menopause women. Osteoporosis is one ofthe major and growing health care problems around the world. One of the first genes to beassociated with the common form of osteoporosis is that for the Vitamin D receptor (VDR ) [1]. This gene encodes the nuclear hormone receptor for vitaminD3 belonging to the family of trans-acting transcriptional regulatory factors. VDRis activated by active form of vitamin D - Calcitriol. Calcitriol isproduced in the kidneys via CYP27B1 by conversion from Calcifediol.
VDR downstream targets are principally involved in mineral metabolism. Theeffects of the vitamin D system on calcium and bone homeostasis are largely mediated bypromoting active intestinal calcium transport via the induction of the epithelial calciumchannel - Transient receptor potential cation channel, subfamily V, member 6 (TRPV6 ) [2]. The accumulation of intracellular calcium generated bythe constitutively open TRPV6 channels, however, impairs further calcium transportactivity of these channels unless this intracellular free calcium is buffered by proteinssuch as Calbindin ( CALB1 ). Transcription of CALB1 is positively regulatedby VDR.
Many essential and typical osteoblast genes are shown to be highly regulated byVDR including RUNX2, Type I collagen alpha 1 ( COL1A1 ),Osteopontin, Osteocalcin. VDR stimulates Ligand for receptoractivator of nuclear factor kappaB ( RANKL )/ Receptor activator of nuclearfactor kappaB ( RANK ) -mediated osteoclastogenesis and bone resorption throughup-regulation of RANKL [2]. Osteoclast-mediated bone resorption couldbe inhibited by Osteoprotegerin ( OPG ) which binds RANKL to preventassociation with its receptor [3].
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