Aggrecan

Aggrecan is a proteoglycan, a protein core carrying many sugar chains called glycosaminoglycans. It is a major component of cartilage matrix and gives the tissue its compressive resistance (Glasson 2005).

The main enzyme that cuts it is ADAMTS5. Mice lacking a working ADAMTS5 had significantly less cartilage destruction after a joint injury (Glasson 2005). MMP13 cuts aggrecan too, at two sites (Fosang 1996).

Researchers draw a line between aggrecan and collagen. Aggrecan loss is thought to be early and reversible, while type II collagen loss is considered irreversible (Li 2011). In mice without MMP13, aggrecan was still lost after injury but cartilage eroded less (Little 2009).

In cell studies, glucosamine sulphate raised aggrecan production by cartilage cells from patients' knees (Dodge 2003), and high leptin lowered the aggrecan gene (Primrose 2023).

Sources

1. Glasson SS, Askew R, Sheppard B et al. Deletion of active ADAMTS5 prevents cartilage degradation in a murine model of osteoarthritis. Nature 2005.
   PMID 15800624DOI 10.1038/nature03369Our summary
2. Fosang AJ, Last K, Knäuper V et al. Degradation of cartilage aggrecan by collagenase-3 (MMP-13). FEBS Lett 1996.
   PMID 8603731DOI 10.1016/0014-5793(95)01539-6Our summary
3. Li NG, Shi ZH, Tang YP et al. New hope for the treatment of osteoarthritis through selective inhibition of MMP-13. Curr Med Chem 2011.
   PMID 21254976DOI 10.2174/092986711794940905Our summary
4. Little CB, Barai A, Burkhardt D et al. Matrix metalloproteinase 13-deficient mice are resistant to osteoarthritic cartilage erosion but not chondrocyte hypertrophy or osteophyte development. Arthritis Rheum 2009.
   PMID 19950295DOI 10.1002/art.25002Our summary
5. Dodge GR, Jimenez SA. Glucosamine sulfate modulates the levels of aggrecan and matrix metalloproteinase-3 synthesized by cultured human osteoarthritis articular chondrocytes. Osteoarthritis Cartilage 2003.
   PMID 12801482DOI 10.1016/s1063-4584(03)00052-9Our summary
6. Primrose JG, Jain L, Bolam SM et al. Concentration-dependent effects of leptin on osteoarthritis-associated changes in phenotype of human chondrocytes. Connect Tissue Res 2023.
   PMID 37171229DOI 10.1080/03008207.2023.2214249Our summary

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