# MMP13 Cartilage Technology

> MMP13 (matrix metalloproteinase-13, collagenase-3) is the enzyme that cuts type II collagen, the scaffold of joint cartilage. Adult cartilage barely replaces that collagen, so what MMP13 cuts stays cut. This site explains the enzyme, what switches it on, and the ingredients studied against it, with every fact cited to a PubMed-indexed paper and labelled by evidence type (human trial, human cells, animal, lab).

## Core pages
- [The enzyme](https://mmp13.com/science): What MMP13 is, how it cuts type II collagen, why that collagen doesn't come back, and what switches the enzyme on.
- [Technology](https://mmp13.com/technology): A formulation technology built around MMP13: soothe, nourish and lubricate, with every active studied against the enzyme.
- [Ingredients](https://mmp13.com/ingredients): Boswellia, curcumin, glucosamine, chondroitin, vitamin C, hyaluronic acid, omega-3 and NAC: what each does and what the research found.
- [Study library](https://mmp13.com/studies): 43 peer-reviewed studies on MMP13 and the ingredients studied against it, labelled by evidence type and linked to PubMed.
- [Questions](https://mmp13.com/questions): Plain answers to common questions about MMP13, cartilage and collagen, each cited to peer-reviewed research on PubMed.
- [Glossary](https://mmp13.com/glossary): Plain-English definitions of the terms used in MMP13 and cartilage research, from aggrecan to type II collagen.
- [About](https://mmp13.com/about): Why this site exists, how we choose and label research, and what it can and can't tell you.

## Questions
- [What is MMP13?](https://mmp13.com/what-is-mmp13): MMP13, short for matrix metalloproteinase-13 and also called collagenase-3, is an enzyme that cuts collagen. Cartilage cells make it, and of the collagen-cutting enzymes it has the highest activity against type II collagen, the fibre that holds joint cartilage together. That is why cartilage researchers single it out.
- [What does MMP13 do to cartilage?](https://mmp13.com/what-does-mmp13-do-to-cartilage): MMP13 cuts type II collagen, the rope-like fibre that gives cartilage its strength. It cleaves each three-stranded collagen molecule at one spot, leaving a three-quarter piece and a one-quarter piece. It also cuts aggrecan, the cushioning molecule. In mice, too much active MMP13 was enough to erode joint cartilage.
- [What is type II collagen?](https://mmp13.com/what-is-type-ii-collagen): Type II collagen is the main collagen in joint cartilage. Collagen makes up about two-thirds of adult cartilage's dry mass, and type II is its principal molecule, woven with smaller amounts of other collagens into a fibre network. On most measurements adults replace that network very slowly, if at all, though one group found faster turnover in ankle cartilage. That slow renewal is why the enzymes that cut it matter.
- [Does cartilage grow back?](https://mmp13.com/does-cartilage-grow-back): Its collagen barely does, on most measurements. Radiocarbon dating of knee cartilage from 23 people found virtually no replacement of the collagen network after the skeleton finished growing, and another study put the half-life of cartilage collagen at 117 years. Some researchers argue cartilage repairs more than that, pointing to faster turnover in ankle cartilage and to repair after knee joint distraction. The cushioning aggrecan is a different story.
- [Is cartilage damage reversible?](https://mmp13.com/is-cartilage-damage-reversible): It depends which part is damaged. Reviews describe losing aggrecan, the water-holding molecule in cartilage, as an early and reversible step, and losing type II collagen as irreversible, because the collagen network renews so slowly in adults. Some researchers argue cartilage can repair more than that, pointing to faster turnover in the ankle and to repair after knee joint distraction.
- [Is joint pain really just wear and tear?](https://mmp13.com/is-joint-pain-really-wear-and-tear): For cartilage, wear and tear is an incomplete picture. Cartilage is broken down by enzymes its own cells make, chiefly MMP13 for the collagen. Healthy cartilage from donors aged 16 to 75 showed no degenerative changes with age. What changes with age is how strongly cartilage cells react when something provokes them.
- [Does MMP13 increase with age?](https://mmp13.com/does-mmp13-increase-with-age): Not on its own. In healthy ankle cartilage from 30 donors aged 16 to 75, all four collagen-cutting enzymes were present but did not change with age. What age changed was the response: cartilage cells from older donors made significantly more MMP13 when provoked with an inflammatory messenger or matrix protein fragments.
- [What switches MMP13 on?](https://mmp13.com/what-switches-mmp13-on): In human cartilage cells, MMP13 rose in response to inflammatory messengers such as IL-1, oxidative stress, calcium phosphate crystals, a disrupted cell body clock, higher glucose and high leptin. In animals, joint injury and mechanical stress did it too. Cells from older donors reacted more strongly to the same triggers.
- [Does inflammation increase MMP13?](https://mmp13.com/does-inflammation-increase-mmp13): Yes, in lab studies. The inflammatory messenger IL-1 raised MMP13 in human cartilage and cartilage cells in several studies, and TNF-alpha did too. To switch the MMP13 gene on, IL-1 needs three signalling routes inside the cell: p38, JNK and NF-kB. Most of this evidence comes from cells in a dish.
- [Does blood sugar affect cartilage?](https://mmp13.com/does-blood-sugar-affect-cartilage): In the lab, it can. University of Auckland researchers found that raising glucose from 4 to 10 mM, within the range from normal to high blood sugar, made cells from damaged knee cartilage produce more MMP13 and ADAMTS5 when oxygen was plentiful. Cells from normal-looking cartilage did not respond the same way.
- [MMP13 vs MMP1: what's the difference?](https://mmp13.com/mmp13-vs-mmp1): Both are collagenases, enzymes that can cut intact collagen, and they cut type II collagen at the same bond. MMP13 is much faster at it: at least ten times faster than MMP-1 in one study and about five times in another. MMP13 also prefers type II collagen, the cartilage kind, and breaks down gelatin well.
- [MMP13 vs ADAMTS5: what's the difference?](https://mmp13.com/mmp13-vs-adamts5): They attack different parts of cartilage. MMP13 is the main enzyme that cuts type II collagen, the fibre network. ADAMTS5 is the main aggrecanase, cutting aggrecan, the molecule that resists squashing. Researchers describe aggrecan loss as early and reversible and collagen loss as irreversible. Mouse studies link each enzyme to cartilage damage.
- [Why is MMP13 a drug target?](https://mmp13.com/why-is-mmp13-a-drug-target): Because it acts at the step reviews call irreversible. MMP13 is the main enzyme cutting type II collagen in damaged cartilage, and that collagen renews very slowly. Mice without MMP13 had less cartilage erosion after injury. Broad MMP-blocking drugs caused joint and muscle side effects in people, so research turned to blocking MMP13 selectively. No MMP13 drug has reached patients.
- [Does curcumin inhibit MMP13?](https://mmp13.com/does-curcumin-inhibit-mmp13): In lab and animal studies, yes. Curcumin lowered MMP13 in rat cartilage cells exposed to IL-1 beta, and a curcumin metabolite bound and blocked MMP13 directly and protected cartilage in rats. No study here measured MMP13 in people taking curcumin, and curcumin taken on its own is poorly absorbed.
- [Does boswellia inhibit MMP13?](https://mmp13.com/does-boswellia-inhibit-mmp13): In animal and lab studies, yes. AKBA, the lead boswellic acid, suppressed MMP13 in rats with chemically induced knee damage, and a frankincense extract lowered MMP13 gene activity in cartilage samples. Human trials of boswellia extracts measured other markers, such as MMP-3 and collagen breakdown fragments, not MMP13 itself.
- [Do glucosamine and chondroitin affect MMP13?](https://mmp13.com/do-glucosamine-and-chondroitin-affect-mmp13): The lab evidence is thin and mixed. Glucosamine lowered MMP13 in one study of human cartilage cells and stem cells, but in another it didn't change cytokine-driven MMP13. Other studies found glucosamine lowered MMP-3 and chondroitin lowered MMP-2 and MMP-9. None of these studies measured MMP13 in people.
- [How does the body keep MMP13 in check?](https://mmp13.com/how-does-the-body-keep-mmp13-in-check): In two main ways. Cells release MMP13 as an inactive proenzyme that must be cut before it works, and the body makes its own inhibitors, the TIMPs. TIMP-1, TIMP-2 and TIMP-3 each blocked active MMP13 one to one in the lab. Healthy cartilage keeps its collagen-cutting enzymes at steady levels.
- [Does MMP13 break down anything besides collagen?](https://mmp13.com/does-mmp13-break-down-anything-besides-collagen): Yes. Besides type II collagen, MMP13 cuts aggrecan, the water-holding molecule in cartilage, at two sites, one of them not seen with other enzymes. Purified MMP13 also broke down gelatin efficiently, unlike the other collagenases. It can cut types I and III collagen too, though five or six times less efficiently than type II.

## Study summaries
- [Collagenase-3, the enzyme now called MMP13, is cloned for the first time](https://mmp13.com/study-freije-1994-collagenase-3-first-cloned): PMID 8207000
- [MMP13 is found in human cartilage cells and cuts type II collagen at least ten times faster than MMP-1](https://mmp13.com/study-mitchell-1996-mmp13-cuts-type-ii-collagen): PMID 8609233
- [Human cartilage cells make collagenase-3, but cells from the joint lining do not](https://mmp13.com/study-reboul-1996-chondrocytes-make-collagenase-3): PMID 8621789
- [Cartilage collagen has an estimated half-life of 117 years](https://mmp13.com/study-verzijl-2000-cartilage-collagen-half-life): PMID 10976109
- [In healthy ankle cartilage, collagen stays in balance as people age](https://mmp13.com/study-aurich-2002-ageing-ankle-cartilage-balance): PMID 12428230
- [Cartilage cells from older donors make more MMP13 when provoked](https://mmp13.com/study-forsyth-2005-older-cartilage-cells-mmp13): PMID 16183949
- [A review of why researchers want drugs that block MMP13 alone](https://mmp13.com/study-li-2011-selective-mmp13-inhibition-review): PMID 21254976
- [Cartilage cells keep their own body clock, and disrupting it raised MMP13](https://mmp13.com/study-snelling-2016-cartilage-cell-body-clock): PMID 27019373
- [Inflammation, oxidative stress and calcium crystals upset the cartilage cell clock and raise MMP13](https://mmp13.com/study-rong-2019-period2-clock-gene-mmp13): PMID 30403881
- [Calcium phosphate crystals raise MMP13 in human cartilage cells through a calcium signal](https://mmp13.com/study-rong-2019-calcium-crystals-raise-mmp13): PMID 30456555
- [A review of MMP13 as a target for protecting cartilage](https://mmp13.com/study-hu-2021-mmp13-target-review): PMID 33572320
- [Oxygen level changes how cells from worn and healthy-looking cartilage behave](https://mmp13.com/study-jain-2023-oxygen-and-cartilage-cells): PMID 37108698
- [High leptin raises MMP13 in human cartilage cells](https://mmp13.com/study-primrose-2023-leptin-raises-mmp13): PMID 37171229
- [Higher glucose pushes cells from worn cartilage to make more MMP13 when oxygen is plentiful](https://mmp13.com/study-jain-2024-glucose-mmp13-adamts5): PMID 38595042
- [A 90-day placebo-controlled trial of a boswellia extract in people with knee osteoarthritis](https://mmp13.com/study-sengupta-2008-boswellia-5-loxin-trial): PMID 18667054
- [Frankincense extract stopped collagen breakdown in cartilage samples in the lab](https://mmp13.com/study-blain-2010-frankincense-cartilage-explants): PMID 19943332
- [Two boswellia extracts compared with placebo over 90 days](https://mmp13.com/study-sengupta-2010-5-loxin-vs-aflapin-trial): PMID 21060724
- [A boswellia extract protected the cartilage matrix in rats](https://mmp13.com/study-shin-2022-boswellia-extract-rats): PMID 36310623
- [A 180-day trial of a boswellia extract measured knee cartilage on MRI](https://mmp13.com/study-kumar-2025-boswellia-mri-cartilage-trial): PMID 39700461
- [Boswellia with celery seed extract lowered collagen breakdown markers over 90 days](https://mmp13.com/study-vaidya-2025-boswellia-celery-seed-trial): PMID 39875757
- [AKBA from boswellia suppressed MMP13 and protected cartilage in rats](https://mmp13.com/study-abo-zalam-2025-akba-mmp13-rats): PMID 41403440
- [Black pepper's piperine raised curcumin absorption by 2000% in human volunteers](https://mmp13.com/study-shoba-1998-piperine-curcumin-absorption): PMID 9619120
- [Curcumin turned down MMP13 and raised type II collagen in rat cartilage cells](https://mmp13.com/study-wang-2017-curcumin-mmp13-rat-chondrocytes): PMID 28627596
- [Curcumin with omega-3 lowered MMP13 in human cartilage cells and conserved cartilage in rats](https://mmp13.com/study-jhun-2025-curcumin-omega-3): PMID 40665304
- [A curcumin metabolite bound and blocked MMP13 and protected cartilage in rats](https://mmp13.com/study-roy-2025-curcumin-monoglucuronide-blocks-mmp13): PMID 40731199
- [Glucosamine raised aggrecan and lowered MMP-3 in cells from patients' knee cartilage](https://mmp13.com/study-dodge-2003-glucosamine-aggrecan-mmp3): PMID 12801482
- [Chondroitin raised type II collagen and enzyme brakes in a human cartilage cell line](https://mmp13.com/study-hsu-2022-chondroitin-human-chondrocytes): PMID 35297475
- [Hyaluronan turned down MMP13 in human cartilage cells through its CD44 receptor](https://mmp13.com/study-julovi-2011-hyaluronan-inhibits-mmp13): PMID 20706991
- [Vitamin C stopped MMP13 rising in cartilage tumour cells and lessened cartilage changes in rats](https://mmp13.com/study-chiu-2016-vitamin-c-chondrocytes): PMID 28035982
- [NAC by mouth held back MMP13 and type II collagen loss in rats](https://mmp13.com/study-kaneko-2019-oral-nac-rats): PMID 31822750
- [Purified collagenase-3 prefers type II collagen and is blocked by the body's TIMPs](https://mmp13.com/study-knauper-1996-collagenase-3-characterised): PMID 8576151
- [MMP13 also cuts aggrecan, the cushioning molecule in cartilage](https://mmp13.com/study-fosang-1996-mmp13-cuts-aggrecan): PMID 8603731
- [IL-1 needs three cell pathways to switch on MMP13 in cartilage cells](https://mmp13.com/study-mengshol-2000-il-1-switches-on-mmp13): PMID 10765924
- [Mice made to produce active MMP13 in their cartilage developed cartilage erosion](https://mmp13.com/study-neuhold-2001-active-mmp13-mice): PMID 11134178
- [What the collagen in joint cartilage is made of](https://mmp13.com/study-eyre-2002-collagen-of-articular-cartilage): PMID 11879535
- [Mice without working ADAMTS5 lost less cartilage after joint injury](https://mmp13.com/study-glasson-2005-adamts5-knockout-mice): PMID 15800624
- [Glucosamine inhibited MMP13 in human cartilage cells and stem cells in the lab](https://mmp13.com/study-derfoul-2007-glucosamine-mmp13-pellets): PMID 17337215
- [A broad MMP-blocking drug brought joint side effects and no clear benefit](https://mmp13.com/study-krzeski-2007-mmp-inhibitor-trial): PMID 17958901
- [Mice without MMP13 resisted cartilage erosion after knee injury](https://mmp13.com/study-little-2009-mmp13-deficient-mice): PMID 19950295
- [A review of the TIMPs, the body's own inhibitors of matrix metalloproteinases](https://mmp13.com/study-brew-2010-timp-family-review): PMID 20080133
- [Glucosamine calmed IL-1 beta in human cartilage cells but did not change MMP13](https://mmp13.com/study-imagawa-2011-glucosamine-epigenetics): PMID 21219853
- [Radiocarbon dating shows adult cartilage collagen is almost never replaced](https://mmp13.com/study-heinemeier-2016-radiocarbon-cartilage-collagen): PMID 27384346
- [A review of ADAMTS5, the main aggrecan-cutting enzyme in cartilage](https://mmp13.com/study-jiang-2021-adamts5-review): PMID 34434966

## Glossary
- [ADAMTS5](https://mmp13.com/glossary-adamts5): ADAMTS5 is the main enzyme that cuts aggrecan, the cushioning molecule in cartilage. It is a separate enzyme family from MMP13, which cuts the collagen.
- [Aggrecan](https://mmp13.com/glossary-aggrecan): Aggrecan is the large water-holding molecule packed into cartilage's collagen network, which lets cartilage resist being squashed. Its loss is described as early and reversible.
- [AKBA](https://mmp13.com/glossary-akba): AKBA is the boswellic acid most studied in boswellia resin research. In rats it suppressed MMP13 and raised the MMP inhibitor TIMP-1.
- [Animal model](https://mmp13.com/glossary-animal-model): An animal model is a laboratory animal, usually a rat or mouse, used to study a process such as cartilage damage that can't be tested the same way in people.
- [Articular cartilage](https://mmp13.com/glossary-articular-cartilage): Articular cartilage is the smooth, firm tissue that covers the ends of bones where they meet in a joint. It is built from a type II collagen network holding the water-retaining molecule aggrecan.
- [Boswellic acids](https://mmp13.com/glossary-boswellic-acids): Boswellic acids are compounds in the gum resin of Boswellia trees, the source of frankincense. AKBA is the most studied of them.
- [Chondrocyte](https://mmp13.com/glossary-chondrocyte): A chondrocyte is the cell that lives inside cartilage and maintains it. Chondrocytes make cartilage's building materials and also the enzymes, including MMP13, that break it down.
- [Chondroitin](https://mmp13.com/glossary-chondroitin): Chondroitin sulphate is a sugar chain found in cartilage, bone, skin and other connective tissue. In a human cartilage cell line it lowered MMP-2 and MMP-9 and raised the inhibitors TIMP-1 and TIMP-2.
- [Collagenase](https://mmp13.com/glossary-collagenase): A collagenase is an enzyme that can cut intact collagen, the tightly wound protein that gives tissues their strength. Humans have three main collagenases: MMP-1, MMP-8 and MMP-13.
- [Curcumin](https://mmp13.com/glossary-curcumin): Curcumin is a compound from the root of turmeric, Curcuma longa. In lab and rat studies it lowered MMP13, and one of its metabolites blocked MMP13 directly.
- [Explant](https://mmp13.com/glossary-explant): An explant is a small piece of living tissue, such as cartilage, taken from the body and kept alive in a dish for experiments. It keeps cells in their natural matrix.
- [Extracellular matrix](https://mmp13.com/glossary-extracellular-matrix): The extracellular matrix is the material cells build around themselves. In cartilage it is the collagen network and aggrecan gel that make up almost all of the tissue.
- [Glucosamine](https://mmp13.com/glossary-glucosamine): Glucosamine is an amino sugar that is a building block of the glycosaminoglycans in cartilage. Lab studies of its effect on MMP13 have given mixed results.
- [Half-life](https://mmp13.com/glossary-half-life): A half-life is the time it takes for half of something to be replaced, broken down or cleared. Cartilage collagen's half-life has been estimated at 117 years.
- [Hyaluronic acid](https://mmp13.com/glossary-hyaluronic-acid): Hyaluronic acid is a long sugar molecule found in joint fluid and cartilage. In human cartilage cells it lowered IL-1 beta-driven MMP13, more at higher doses.
- [IL-1 beta](https://mmp13.com/glossary-il-1-beta): IL-1 beta is a messenger protein, or cytokine, released during inflammation. It is the trigger most cartilage studies use to switch on MMP13 in cells.
- [In vitro](https://mmp13.com/glossary-in-vitro): In vitro means done outside a living body, in a dish or test tube. Most MMP13 research is in vitro, using cartilage cells or purified enzymes.
- [Matrix metalloproteinase](https://mmp13.com/glossary-matrix-metalloproteinase): Matrix metalloproteinases, or MMPs, are a family of zinc-dependent enzymes that break down proteins in the material around cells. MMP13 is one of them.
- [MMP13](https://mmp13.com/glossary-mmp13): MMP13 is an enzyme made by cartilage cells that cuts type II collagen, the main fibre of joint cartilage. Of the collagen-cutting enzymes it has the highest activity against type II collagen.
- [N-acetyl-cysteine](https://mmp13.com/glossary-n-acetyl-cysteine): N-acetyl-cysteine, or NAC, is an antioxidant compound. Given by mouth to rats, it held back MMP13 and the loss of type II collagen in a joint damage model.
- [NF-kB](https://mmp13.com/glossary-nf-kb): NF-kB is a control protein inside cells that switches on inflammation-related genes when it moves into the nucleus. MMP13 is one of the genes it helps switch on.
- [Piperine](https://mmp13.com/glossary-piperine): Piperine is the compound in black pepper that slows the body's breakdown of some other compounds. Taken with curcumin, it raised curcumin absorption by 2000% in human volunteers.
- [Randomised controlled trial](https://mmp13.com/glossary-randomised-controlled-trial): A randomised controlled trial assigns people by chance to a treatment or a comparison such as a placebo, so differences in outcome can be credited to the treatment. Double-blind means neither participants nor researchers know who got which.
- [TIMP](https://mmp13.com/glossary-timp): TIMPs, tissue inhibitors of metalloproteinases, are the body's own blockers of MMPs and related enzymes. Humans have four, TIMP-1 to TIMP-4.
- [Type II collagen](https://mmp13.com/glossary-type-ii-collagen): Type II collagen is the main collagen in joint cartilage, forming the fibre network that gives cartilage its strength. In adults it is replaced very slowly.