Journal article
Co-localization of insulin-like growth factor binding protein 3 and fibronectin in human articular cartilage
Osteoarthritis and cartilage, Vol.10(7), pp.556-563
07/2002
DOI: 10.1053/joca.2002.0791
PMID: 12127836
Abstract
The anabolic cytokine insulin-like growth factor I (IGF-I) stimulates chondrocyte synthesis of matrix macromolecules and several lines of evidence suggest that it has a major role in maintaining articular cartilage and possibly in cartilage repair. Despite the apparent importance of IGF-I in articular cartilage metabolism and its potential importance in joint diseases, little is known about the regulation of IGF-I activity within the tissue. Insulin-like growth factor binding proteins (IGFBPs) bind IGF-I and can modify its activity. At least three IGFBPs are expressed by chondrocytes: IGFBP-3, -4 and -5. Localization of IGFPBs in the articular cartilage extracellular matrix (ECM) could create reservoirs of IGF-I within the articular cartilage ECM and thereby regulate local IGF-I levels. We hypothesized that ECM molecules bind and concentrate IGFPBs in the pericellular/territorial matrix.
Semi-quantitative immunohistological measures of co-localization were used to compare the spatial distribution of IGFBP-3, -4, and -5 with the distributions of three peri-cellularly-enriched matrix molecules fibronectin, tenascin-C, and type VI collagen in osteoarthritic and non-osteoarthritic human articular cartilage. Purified proteins were used in an agarose diffusion assay to compare IGFBP-3 binding to the same three matrix proteins.
IGFBP-3 associated with fibronectin in the pericellular/territorial matrix (approximately 40% co-localization) but not with tenascin-C, or type VI collagen (approximately 6% and approximately 15% co-localization respectively, P< 0.05). Neither IGFBP-4, nor IGFBP-5 were associated with any of the three ECM proteins (P< 0.05). In agarose diffusion assays IGFBP-3 interacted with fibronectin and heparan sulfate proteoglycan but not with type VI collagen or tenascin-C.
Direct binding between purified IGFBP-3 and fibronectin and the strong co-localization the two proteins in the cartilage matrix support the hypothesis that IGFPB-3 and fibronectin help regulate local IGF-I levels.
Details
- Title: Subtitle
- Co-localization of insulin-like growth factor binding protein 3 and fibronectin in human articular cartilage
- Creators
- J A Martin - Iowa City Veterans Administration Medical Center and University of Iowa Department of Orthopaedics, Iowa City, USAB A MillerM B ScherbL A LembkeJ A Buckwalter
- Resource Type
- Journal article
- Publication Details
- Osteoarthritis and cartilage, Vol.10(7), pp.556-563
- DOI
- 10.1053/joca.2002.0791
- PMID
- 12127836
- NLM abbreviation
- Osteoarthritis Cartilage
- ISSN
- 1063-4584
- eISSN
- 1522-9653
- Publisher
- England
- Language
- English
- Date published
- 07/2002
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Stead Family Department of Pediatrics; Pharmaceutical Sciences and Experimental Therapeutics; Orthopedics and Rehabilitation; Physical Therapy and Rehabilitation Science; Injury Prevention Research Center
- Record Identifier
- 9984040537102771
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