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Clinical significance
- Articular Cartilage Collagen: an irreplaceable framework?

Knowledge of the molecular structure of the collagenous framework of articular cartilage and how it grows, remodels and matures through its various pericellular, territorial, and interterritorial domains is essential for understanding mechanisms of its breakdown in disease. The extent to which chondrocytes can remodel this crosslinked polymer in the adult joint and whether pericellular/ territorial collagen is the primary target of such remodelling or the remote interterritorial matrix as well, are open questions. Accelerated synthesis (and breakdown) of collagen is evident in OA and begins within hours after joint injury, but needs to be understood better in terms of where new deposition occurs in the microarchitecture of the matrix and in molecular detail. If increased collagen synthesis is directed at the deposition of new fibrils having the high proportion of collagen types IX and XI seen in developing cartilage, then control mechanisms of gene expression and protein assembly in the adult may be more susceptible to the effects of genetic variations (polymorphisms) than during skeletogenesis. Osteoarthritic disease progression might be particularly rapid in individuals with a genotype that compromises the ability of mature chondrocytes to repair and remodel their matrix after joint trauma.

The covalent addition of type III collagen to the polymeric matrix of articular cartilage of adult human joints suggests an active remodelling process. It occurs in both normal and osteoarthritic joints, but whether it signals pathological events or a healthy repair mechanism is not known. In considering tissue engineering strategies and the feasibility of promoting articular cartilage repair or formation de novo in an adult joint, the complex collagen architecture and unique molecular phenotype are clearly a challenge to recreate and a candidate benchmark of success.


This work was supported in part by grants from the National Institutes of Health and the Burgess Chair Endowment of the University of Washington.

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