Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
1999-12-20
pubmed:abstractText
Insulin-like growth factor (IGF)-binding protein-4 (IGFBP-4), one of the most abundant IGFBPs produced by bone cells, is a potent inhibitor of IGF actions in vitro. To evaluate the modulation of IGF actions on bone formation in vivo by IGFBP-4, we produced intact and fragment (50- to 100-fold reduced IGF affinity) forms of BP-4 and examined their local and systemic effects using biochemical markers. Local administration of IGF-I over the right parietal bone significantly increased bone extract alkaline phosphatase activity; this was completely blocked by an equimolar dose of intact IGFBP-4, but not IGFBP-4 fragment. A single sc administration of IGF-I (2 microg/g BW) significantly increased bone formation markers in both serum and skeletal extracts; surprisingly, so did intact IGFBP-4, but not fragment IGFBP-4. Subcutaneous administration of an equimolar dose of IGFBP-4 along with IGF-I did not significantly block the IGF-I effect. Administration of intact IGFBP-4 significantly increased the serum 50-kDa IGF pool and decreased the 150-kDa IGF pool without significantly changing total IGF-I. We postulate that the increase in the 50-kDa IGF pool might enhance IGFs bioavailability via a mechanism involving IGFBP-4-specific protease. This study demonstrates for the first time that a single local administration of IGFBP-4 inhibits IGF-I-induced increases in bone formation, whereas systemic administration of IGFBP-4 alone increases serum levels of bone formation markers.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0013-7227
pubmed:author
pubmed:issnType
Print
pubmed:volume
140
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5719-28
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Effects of recombinant insulin-like growth factor-binding protein-4 on bone formation parameters in mice.
pubmed:affiliation
Musculoskeletal Disease Center, J. L. Pettis Veterans Administration Medical Center, Loma Linda, California 92357, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't