Linked Life Data

11356715

Source:http://linkedlifedata.com/resource/pubmed/id/11356715

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2001-5-17
pubmed:abstractText
Insulin-like growth factor (IGF)-binding protein-4 (IGFBP-4) is a potent inhibitor of IGF actions in vitro. However, we found that systemic administration of IGFBP-4 at pharmacological doses caused a significant increase in bone formation parameters in mice by a mechanism that may involve increased IGF bioavailability via proteolysis of IGFBP-4. To evaluate the hypothesis that proteolysis of IGFBP-4 is essential for the stimulatory effects of systemically administered IGFBP-4, we produced wild-type, protease-resistant, and IGFBP-4 proteolytic fragments and evaluated their effects using biochemical markers. Protease-resistant IGFBP-4 was more potent than wild-type IGFBP-4 in inhibiting IGF-I-induced mouse osteoblast cell proliferation in vitro and in inhibiting IGF-I-induced increase in alkaline phosphatase (ALP) activity in bone extract after local administration in vivo. Systemic administration of wild-type IGFBP-4, but not protease-resistant IGFBP-4, increased serum osteocalcin, serum ALP, and ALP in skeletal extracts in a dose-dependent manner, with a maximal effect of 40% (P < 0.05) at 1.25 nmol/mouse. Systemic administration of wild-type, but not protease-resistant, IGFBP-4 increased free IGF-I levels in serum in normal mice. IGF-I, but not wild-type IGFBP-4, increased bone formation parameters in IGF-I-deficient mice. This study demonstrates that systemic administration of IGFBP-4 increases bone formation parameters in mice by increasing IGF bioavailability in the circulation via an IGFBP-4 protease-dependent mechanism.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0013-7227
pubmed:author
pubmed:issnType
Print
pubmed:volume
142
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2641-8
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:11356715-Alkaline Phosphatase, pubmed-meshheading:11356715-Animals, pubmed-meshheading:11356715-Biological Availability, pubmed-meshheading:11356715-Blood Glucose, pubmed-meshheading:11356715-Bone Development, pubmed-meshheading:11356715-Bone and Bones, pubmed-meshheading:11356715-Cell Division, pubmed-meshheading:11356715-Cells, Cultured, pubmed-meshheading:11356715-Female, pubmed-meshheading:11356715-Humans, pubmed-meshheading:11356715-Insulin-Like Growth Factor Binding Protein 4, pubmed-meshheading:11356715-Insulin-Like Growth Factor I, pubmed-meshheading:11356715-Metalloendopeptidases, pubmed-meshheading:11356715-Mice, pubmed-meshheading:11356715-Mice, Inbred C3H, pubmed-meshheading:11356715-Osteoblasts, pubmed-meshheading:11356715-Osteocalcin, pubmed-meshheading:11356715-Peptide Fragments, pubmed-meshheading:11356715-Pregnancy-Associated Plasma Protein-A, pubmed-meshheading:11356715-Recombinant Proteins
pubmed:year
2001
pubmed:articleTitle
Systemic administration of insulin-like growth factor (IGF)-binding protein-4 (IGFBP-4) increases bone formation parameters in mice by increasing IGF bioavailability via an IGFBP-4 protease-dependent mechanism.
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, Non-U.S. Gov't