? The ability of cartilage to withstand mechanical stress depends on the quality of the type II/IX/XI collagen heterofibrillar network that frames cartilage. In arthritis, progressive degradation of this network leads to a loss of normal joint function since cartilage has a limited capacity to heal. In the new field of research, cartilage tissue engineering, which has the ambitious goal of stimulating cartilage repair in vivo or growing cartilage tissue in vitro to resurface or reconstruct joints, it is known that cartilage cells can be induced to synthesize and form a matrix based on type II collagen. To what degree the fibrillar matrix is normal, in terms of the correct assemblies of minor collagens (types IX and XI) with type II collagen is not well characterized. The goal of this study is to use methods in protein chemistry to establish a molecular fingerprint of collagen heterofibril assembly as a biomarker for normal and engineered cartilage.
The aim i s to investigate the ability of chondrocytes, cultured under suitable conditions or induced with fibroblast growth factor-18, to assemble collagen types II, IX and XI into the co-polymeric cross-linked network that typifies hyaline cartilage in vivo. Since each of the minor collagens is essential in regulating the organization of the network, fingerprinting the pattern of inter-type cross-linking provides a screen for normal matrix assembly. This will be invaluable in understanding the temporal sequence of events in fibrillogenesis of the type II collagen heterofibril and lay the foundation for assessing the changing quality of cartilage in disease, when produced as a healing response or when induced by tissue engineering methods. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Small Research Grants (R03)
Project #
5R03AR052896-03
Application #
7242645
Study Section
Special Emphasis Panel (ZAR1-EHB-E (M1))
Program Officer
Tyree, Bernadette
Project Start
2005-07-01
Project End
2009-06-30
Budget Start
2007-07-01
Budget End
2009-06-30
Support Year
3
Fiscal Year
2007
Total Cost
$71,872
Indirect Cost
Name
University of Washington
Department
Orthopedics
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Hrabe, Nikolas W; Heinl, Peter; Bordia, Rajendra K et al. (2013) Maintenance of a bone collagen phenotype by osteoblast-like cells in 3D periodic porous titanium (Ti-6Al-4 V) structures fabricated by selective electron beam melting. Connect Tissue Res 54:351-60
Seegmiller, Robert E; Bomsta, Brandon D; Bridgewater, Laura C et al. (2008) The heterozygous disproportionate micromelia (dmm) mouse: morphological changes in fetal cartilage precede postnatal dwarfism and compared with lethal homozygotes can explain the mild phenotype. J Histochem Cytochem 56:1003-11
Fernandes, Russell J; Weis, Maryann; Scott, Melissa A et al. (2007) Collagen XI chain misassembly in cartilage of the chondrodysplasia (cho) mouse. Matrix Biol 26:597-603
Hjorten, Rebecca; Hansen, Uwe; Underwood, Robert A et al. (2007) Type XXVII collagen at the transition of cartilage to bone during skeletogenesis. Bone 41:535-42
Fernandes, Russell J; Harkey, Michael A; Weis, Maryann et al. (2007) The post-translational phenotype of collagen synthesized by SAOS-2 osteosarcoma cells. Bone 40:1343-51