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Chondroadherin binds to type II collagen
Arthritis Research & Therapy volume 3, Article number: 72650 (2001)
Context
Chondroadherin belongs to a family of small leucine-rich repeat (LRR) proteoglycans that is a major component of the cartilage matrix. This family also includes biglycan, decorin, fibromodulin, and lumican. Type II collagen (CII) is the major collagenous component in cartilage; previous studies have demonstrated binding of CII with several LRR proteins, as well as to cartilage oligomeric matrix protein. This study tested the hypothesis that chondroadherin binds to CII.
Significant findings
Chondroadherin was 36 kDa in monomeric form, and 67 kDa in dimeric form. CII and chondroadherin were found to co-fractionate and were detected in tightly associated complexes. Chondroadherin was bound to specific sites on the collagen fibrils, at 185 nm and 267 nm from the C-terminal end of the collagen. These associations were similar in both extracted complexes from in vivo materials, and in reconstituted complexes from pure proteins. The equilibrium dissociation constant for this interaction was 40 nM.
Comments
This report demonstrated definitively that chondroadherin binds to CII. Furthermore, based on extraction from biological materials, and the intactness of the extracted complexes, this report provided strong evidence that binding may also occur in vivo. The most significant implication from this study is that as chondroadherin is a territorial component, its binding to CII suggests that this complex may have cell regulatory function, in addition to structural functions. The cell regulatory function may be mediated by the complexes in association with a2-?1 integrins that are expressed on the cell surface of chondrocytes. Chondroadherin is localized in a restrictive manner in the late proliferative cells of the growth plate, and to the developing articular cartilage (see Additional information [1]). This further suggests that the interactions between chondroadherin and collagen may regulate chondrocyte growth and proliferation. In addition to chondroadherin, several other LRR proteins are also bound to collagen fibrils. Targeted disruption of biglycan in mice leads to loss of integrity of the collagen network and an osteoporosis-like phenotype (see Additional information [2]). Altered levels of biglycan, decorin and fibromodulin were detected in an experimental osteoarthritic model (see Additional information [3]). Therefore, another significant implication from the current study is that chondroadherin contributes to the integrity of collagen network by regulating the assembly. Deregulation of chondroadherin may then lead to congenital skeletal disorder, or cartilage degenerative diseases such as arthritis. The biochemical interactions of chondroadherin and collagen may represent yet another mechanism for collagen homeostasis.
Methods
Molecular cloning, sequencing, expression of recombinant chondroadherin, generation of antibodies, biochemical extraction and purification, ion exchange chromatography, zonal rate centrifugation in glycerol gradients, SDS-PAGE, western blotting, transmission electron microscopy, surface plasmon resonance
Additional information
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1.
Shen Z, Gantcheva S, Mansson B, Heinegard D, Sommarin Y: Chondroadherin expression changes in skeletal development.
Biochem J 1998, 330:549-557 (PubMed abstract).
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2.
Xu T, Bianco P, Fisher LW, Longenecker G, Smith E, Goldstein S, Bonadio J, Boskey A, Heegaard AM, Sommer B, Satomura K, Dominguez P, Zhao C, Kulkarni AB, Robey PG, Young MF: Targeted disruption of the biglycan gene leads to an osteoporosis-like phenotype in mice.
Nat Genet 1998, 20:78-82 (PubMed abstract).
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3.
Dourado GS, Adams ME, Matyas JR, Huang D: Expression of biglycan, decorin and fibromodulin in the hypertrophic phase of experimental osteoarthritis.
Osteoarthritis Cartilage 1996, 4:187-196 (PubMed abstract).
Genebank entry, human chondroadherin, AF371328
Online Mendelian Inheritance in Man, entry 602178 Chondroadherin
References
- 1.
Mansson B, Wenglen C, Morgelin M, Saxne T, Heinegard D: Association of chondroadherin with collagen type II. J Biol Chem. 2001, 276: 32883-32888.
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Shum, L. Chondroadherin binds to type II collagen. Arthritis Res Ther 3, 72650 (2001). https://doi.org/10.1186/ar-2001-72650
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Keywords
- Articular cartilage
- binding assay
- chondroadherin
- protein extraction
- type II collagen
