Matrix metalloproteinase

MMPs share a common build. Each has a zinc-binding site at its working centre and a short stretch that keeps the enzyme switched off until it is activated (Freije 1994). They are released as inactive proenzymes and become active when part of the molecule is cut away (Knäuper 1996).

The family divides into groups by what they cut. The collagenases (MMP-1, MMP-8, MMP-13) cut intact collagen (Freije 1994), while others such as MMP-3, MMP-2 and MMP-9 appear in cartilage studies as markers of matrix breakdown (Dodge 2003; Hsu 2022).

The body controls MMPs with its own inhibitors, the TIMPs (Brew 2010). Drugs that blocked many MMPs at once caused musculoskeletal side effects in people without clear benefit (Krzeski 2007), which is why research moved to blocking MMP13 selectively (Li 2011).

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. 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
3. 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
4. Hsu HC, Ke YL, Lai YH et al. Chondroitin Sulfate Enhances Proliferation and Migration via Inducing β-Catenin and Intracellular ROS as Well as Suppressing Metalloproteinases through Akt/NF-κB Pathway Inhibition in Human Chondrocytes. J Nutr Health Aging 2022.
   PMID 35297475DOI 10.1007/s12603-022-1752-5Our summary
5. Brew K, Nagase H. The tissue inhibitors of metalloproteinases (TIMPs): an ancient family with structural and functional diversity. Biochim Biophys Acta 2010.
   PMID 20080133DOI 10.1016/j.bbamcr.2010.01.003Our summary
6. Krzeski P, Buckland-Wright C, Bálint G et al. Development of musculoskeletal toxicity without clear benefit after administration of PG-116800, a matrix metalloproteinase inhibitor, to patients with knee osteoarthritis: a randomized, 12-month, double-blind, placebo-controlled study. Arthritis Res Ther 2007.
   PMID 17958901DOI 10.1186/ar2315Our summary
7. 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

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