MMP13

MMP13 was cloned in 1994 from breast tumour tissue and named collagenase-3, as the third human collagenase known (Freije 1994). In 1996 two groups showed that human cartilage cells make it (Mitchell 1996; Reboul 1996). It turned over type II collagen at least ten times faster than MMP-1 (Mitchell 1996) and prefers type II collagen to types I and III (Knäuper 1996).

Cells release it as an inactive proenzyme that has to be cut to become active, and the body's TIMP inhibitors block it one to one (Knäuper 1996). Mice made to produce always-active MMP13 in their cartilage developed cartilage erosion (Neuhold 2001), while mice lacking it had less erosion after a knee injury (Little 2009).

Reviews call it the primary MMP in cartilage breakdown (Hu 2021) and the major collagenase in damaged cartilage (Li 2011), which makes it a drug target. Inflammatory messengers, calcium crystals, glucose and leptin are among the things that raise it in human cartilage cells (Mengshol 2000; Rong 2019; Jain 2024; Primrose 2023).

Sources

1. Freije JM, Díez-Itza I, Balbín M et al. Molecular cloning and expression of collagenase-3, a novel human matrix metalloproteinase produced by breast carcinomas. J Biol Chem 1994.
   PMID 8207000Our summary
2. Mitchell PG, Magna HA, Reeves LM et al. Cloning, expression, and type II collagenolytic activity of matrix metalloproteinase-13 from human osteoarthritic cartilage. J Clin Invest 1996.
   PMID 8609233DOI 10.1172/JCI118475Our summary
3. Reboul P, Pelletier JP, Tardif G et al. The new collagenase, collagenase-3, is expressed and synthesized by human chondrocytes but not by synoviocytes. A role in osteoarthritis. J Clin Invest 1996.
   PMID 8621789DOI 10.1172/JCI118636Our summary
4. Knäuper V, López-Otin C, Smith B et al. Biochemical characterization of human collagenase-3. J Biol Chem 1996.
   PMID 8576151DOI 10.1074/jbc.271.3.1544Our summary
5. Neuhold LA, Killar L, Zhao W et al. Postnatal expression in hyaline cartilage of constitutively active human collagenase-3 (MMP-13) induces osteoarthritis in mice. J Clin Invest 2001.
   PMID 11134178DOI 10.1172/JCI10564Our summary
6. 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
7. Hu Q, Ecker M. Overview of MMP-13 as a Promising Target for the Treatment of Osteoarthritis. Int J Mol Sci 2021.
   PMID 33572320DOI 10.3390/ijms22041742Our summary
8. 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
9. Mengshol JA, Vincenti MP, Coon CI et al. Interleukin-1 induction of collagenase 3 (matrix metalloproteinase 13) gene expression in chondrocytes requires p38, c-Jun N-terminal kinase, and nuclear factor kappaB: differential regulation of collagenase 1 and collagenase 3. Arthritis Rheum 2000.
   PMID 10765924DOI 10.1002/1529-0131(200004)43:4<801::AID-ANR10>3.0.CO;2-4Our summary
10. Rong J, Pool B, Zhu M et al. Basic Calcium Phosphate Crystals Induce Osteoarthritis-Associated Changes in Phenotype Markers in Primary Human Chondrocytes by a Calcium/Calmodulin Kinase 2-Dependent Mechanism. Calcif Tissue Int 2019.
    PMID 30456555DOI 10.1007/s00223-018-0494-1Our summary
11. Jain L, Bolam SM, Monk P et al. Elevated glucose promotes MMP13 and ADAMTS5 production by osteoarthritic chondrocytes under oxygenated but not hypoxic conditions. J Cell Physiol 2024.
    PMID 38595042DOI 10.1002/jcp.31271Our summary
12. 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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