Linked Life Data

16183342

Source:http://linkedlifedata.com/resource/pubmed/id/16183342

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2005-12-12
pubmed:abstractText
The IGF axis is important for long bone development, homeostasis and disease. The activities of IGF-I and IGF-II are regulated by IGF binding proteins (IGFBPs). IGF-I and IGFBP2 are co-expressed in dynamic fashions in the developing long bones of the chick wing, and we have found that IGF-II is present in the cartilage model and surrounding perichondrium, proliferative and hypertrophic chondrocytes and developing periosteum. To gain insight into endogenous roles of IGF-I, IGF-II and IGFBP2 in long bone development, we have overexpressed IGFBP2 in the developing skeletal elements of the embryonic chick wing in vivo, using an RCAS retroviral vector. IGFBP2 overexpression led to an obvious shortening of the long bones of the wing. We have investigated, at the cellular and molecular levels, the mechanism of action whereby IGFBP2 overexpression impairs long bone development in vivo. At an early stage, IGFBP2 excess dramatically inhibits proliferation by the chondrocytes of the cartilage models that prefigure the developing long bones. Later, IGFBP2 excess also reduces proliferation of the maturing chondrocytes and attenuates proliferation by the perichondrium/developing periosteum. IGFBP2 excess does not affect morphological or molecular indicators of chondrocyte maturation, osteoblast differentiation or cell/matrix turnover, such as expression of Ihh, PTHrP, type X collagen and osteopontin, or distribution and relative abundance of putative clast cells. We also have found that IGFBP2 blocks the ability of IGF-I and IGF-II to promote proliferation and matrix synthesis by wing chondrocytes in vitro. Together, our results suggest that the mechanism of action whereby IGFBP2 excess impairs long bone development is to inhibit IGF-mediated proliferation and matrix synthesis by the cartilage model; reduce the proliferation and progression to hypertrophy by the maturing chondrocytes; and attenuate proliferation and formation of the periosteal bony collar. These actions retard the growth and longitudinal expansion of the developing long bones, resulting in shortened wing skeletal elements. Our results emphasize the importance of a balance of IGF/IGFBP2 action at several stages during normal long bone development.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
8756-3282
pubmed:author
pubmed:issnType
Print
pubmed:volume
37
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
741-50
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Role of IGFBP2, IGF-I and IGF-II in regulating long bone growth.
pubmed:affiliation
Center for Limb and Skeletal Development, Department of BioStructure and Function, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural