Linked Life Data

17595320

Source:http://linkedlifedata.com/resource/pubmed/id/17595320

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2007-10-1
pubmed:abstractText
The 1,25 dihydroxyvitamin D3 [1,25(OH)2D3]-induced differentiation of osteoblasts comprises the sequential induction of cell cycle arrest at G0/G1 and the expression of bone matrix proteins. Reports differ on the effects of IGF binding protein (IGFBP)-5 on bone cell growth and osteoblastic function. IGFBP-5 can be growth stimulatory or inhibitory and can enhance or impair osteoblast function. In previous studies, we have shown that IGFBP-5 localizes to the nucleus and interacts with the retinoid receptors. We now show that IGFBP-5 interacts with nuclear vitamin D receptor (VDR) and blocks retinoid X receptor (RXR):VDR heterodimerization. VDR and IGFBP-5 were shown to colocalize to the nuclei of MG-63 and U2-OS cells and coimmunoprecipitate in nuclear extracts from these cells. Induction of osteocalcin promoter activity and alkaline phosphatase activity by 1,25(OH)2D3 were significantly enhanced when IGFBP-5 was down-regulated in U2-OS cells. Moreover, we found IGFBP-5 increased basal alkaline phosphatase activity and collagen alpha1 type 1 expression, and that 1,25(OH)2D3 was unable to further induce the expression of these bone differentiation markers in MG-63 cells. Expression of IGFBP-5 inhibited MG-63 cell growth and caused cell cycle arrest at G0/G1 and G2/M. Furthermore, IGFBP-5 reduced the effects of 1,25(OH)2D3 in blocking cell cycle progression at G0/G1 and decreased the expression of cyclin D1. These results demonstrate that IGFBP-5 can interact with VDR to prevent RXR:VDR heterodimerization and suggest that IGFBP-5 may attenuate the 1,25(OH)2D3-induced expression of bone differentiation markers while having a modest effect on the 1,25(OH)2D3-mediated inhibition of cell cycle progression in bone cells.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0888-8809
pubmed:author
pubmed:issnType
Print
pubmed:volume
21
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2378-90
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:17595320-Alkaline Phosphatase, pubmed-meshheading:17595320-Biological Markers, pubmed-meshheading:17595320-Calcitriol, pubmed-meshheading:17595320-Cell Cycle, pubmed-meshheading:17595320-Cell Differentiation, pubmed-meshheading:17595320-Cell Nucleus, pubmed-meshheading:17595320-Cells, Cultured, pubmed-meshheading:17595320-Collagen Type I, pubmed-meshheading:17595320-Dimerization, pubmed-meshheading:17595320-Humans, pubmed-meshheading:17595320-Insulin-Like Growth Factor Binding Protein 5, pubmed-meshheading:17595320-Ligands, pubmed-meshheading:17595320-Osteoblasts, pubmed-meshheading:17595320-Osteocalcin, pubmed-meshheading:17595320-Promoter Regions, Genetic, pubmed-meshheading:17595320-Receptors, Calcitriol, pubmed-meshheading:17595320-Retinoid X Receptor alpha, pubmed-meshheading:17595320-Vitamin D, pubmed-meshheading:17595320-Vitamin D Response Element
pubmed:year
2007
pubmed:articleTitle
Insulin-like growth factor binding protein-5 interacts with the vitamin D receptor and modulates the vitamin D response in osteoblasts.
pubmed:affiliation
Kolling Institute of Medical Research, Royal North Shore Hospital, St. Leonards, New South Wales 2065, Australia. lyns@med.usyd.edu.au
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't