MMP13 vs MMP1: what's the difference?

Three collagenases

Only a few enzymes can cut the tightly wound collagen molecule. Three are known as collagenases: MMP-1, MMP-8 and MMP-13 (Roy 2025). MMP-1 is the fibroblast collagenase and MMP-8 the neutrophil collagenase (Knäuper 1996). When MMP13 was cloned in 1994 it was the third member of the group, so it was named collagenase-3 (Freije 1994).

Same cut, different speed

MMP13 and MMP-1 cleave type II collagen at the same bond, giving the characteristic three-quarter and one-quarter fragments. MMP13 then makes a second cut that trims three amino acids from the shorter piece (Mitchell 1996).

The big difference is speed. Mitchell and colleagues found that MMP13 turned over type II collagen at least ten times faster than MMP-1 (Mitchell 1996). Reboul and colleagues measured a catalytic rate about five times higher (Reboul 1996). The two studies used different methods, so the exact figure differs, but both put MMP13 well ahead.

Different tastes in collagen

Purified human MMP13 preferred soluble type II collagen and was five or six times less efficient at cutting types I and III (Knäuper 1996). On fibrillar type I collagen it was about as efficient as MMP-1 and MMP-8 (Knäuper 1996). Unlike those two, MMP13 also broke down gelatin and two test peptides efficiently, which fits its active site resembling the gelatinases (Knäuper 1996). It cuts aggrecan as well (Fosang 1996).

Where they are made

Both turn up in cartilage. In worn human cartilage, levels of MMP13 and MMP-1 varied, and the inflammatory messenger IL-1 alpha significantly raised both (Mitchell 1996). Earlier work had suggested MMP-1 contributes to cartilage collagen breakdown. After finding MMP13 in chondrocytes and measuring its speed on type II collagen, Mitchell's group concluded that MMP13 plays a significant role in that breakdown (Mitchell 1996). Human chondrocytes from damaged cartilage made about 9.5 times as much collagenase-3 protein as those from normal cartilage (Reboul 1996).

Different switches

The two genes are switched on differently. In cartilage cells, IL-1 needed p38, JNK and NF-kB to turn on MMP13. MMP-1 relied on a different combination of routes, which also varied between cell types (Mengshol 2000). That matters to researchers, because a compound that calms one route might affect one collagenase and not the other.

Which one matters more for cartilage

Reviews now name MMP13 the major collagenase in damaged cartilage, with the highest activity against type II collagen (Li 2011), and the primary MMP involved in cartilage breakdown (Hu 2021). MMP-1 isn't irrelevant. Curcumin with omega-3 lowered MMP-1, MMP-3 and MMP13 together in human cartilage cells (Jhun 2025), and a 2025 study argued that blocking MMP-8 as well as MMP13 matters for protecting cartilage (Roy 2025).

Other questions people ask

Sources

1. Roy HS, Kulkarni C, Neethu KM et al. Curcumin monoglucuronide protects cartilage from progressive degeneration by blocking MMP-13. Arch Pharm Res 2025.
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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. 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
4. 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
5. 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.
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6. 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
7. 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
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. 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
10. Jhun J, Lee D, Na HS et al. Curcumin and omega-3 ameliorate experimental osteoarthritis progression in terms of joint pain and mitochondrial dysfunction. J Inflamm (Lond) 2025.
    PMID 40665304DOI 10.1186/s12950-025-00453-xOur summary

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