Is joint pain really just 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.
What wear and tear implies
The phrase pictures cartilage as a tread that thins with use until it's gone. The research on this site measures cartilage, its collagen and the enzymes that cut it, not pain, so it can only speak to the cartilage half of the question. On that half, it describes something more active than rubbing away.
Richard Loeser starts from the same picture, a car tyre, and then points to the difference.
The big difference between your joints and an automobile tire is that your joints are made up of living tissues, and so it's the tissues themselves that are changing and developing osteoarthritis, meaning that it's not just simply a wearing down, but the cells within the tissue are releasing factors that cause the breakdown of the tissue.
Cartilage is taken apart by enzymes
Cartilage cells make the enzymes that break cartilage down. In 1996, two groups showed that human chondrocytes make MMP13 (Mitchell 1996; Reboul 1996). Of the collagen-cutting enzymes, MMP13 has the highest activity against type II collagen, the fibre network of cartilage (Li 2011), and reviews now name it the primary MMP in cartilage breakdown (Hu 2021). Mice made to produce extra active MMP13 in their cartilage developed cartilage erosion (Neuhold 2001). Mice lacking it had less erosion after a knee injury (Little 2009).
Age alone doesn't do it
If cartilage simply wore out, older cartilage should look progressively worn. A study of healthy ankle cartilage from 30 donors aged 16 to 75 found otherwise. Type II collagen and proteoglycan content didn't change after 30, all four collagenases were present but didn't change with age, and collagen synthesis and breakdown stayed at a steady state (Aurich 2002). The authors wrote that they found no molecular evidence of degenerative changes, which set ageing apart from the disease process.
What age did change, in a 2005 study, was the cells' reaction. Cartilage cells from older donors made significantly more MMP13 than cells from younger donors when provoked with an inflammatory messenger or fragments of a matrix protein (Forsyth 2005).
Then what provokes the cells?
Many things, in lab studies of human cartilage cells:
- inflammatory messengers such as IL-1 and TNF-alpha (Reboul 1996);
- oxidative stress and calcium phosphate crystals (Rong 2019; Rong 2019);
- a disrupted body clock inside the cells (Snelling 2016);
- higher glucose, and leptin at levels the authors linked to joint fluid in metabolic syndrome (Jain 2024; Primrose 2023).
Each of these raised MMP13. Several of the studies came from the University of Auckland.
Where use does come in
Load still matters, but the research describes it acting through the cells rather than by abrasion. In rats, mechanical stress led to a build-up of reactive oxygen species in cartilage cells, cell death and joint changes, and in cultured cells mechanical stress raised oxidative stress and inflammatory messengers (Kaneko 2019). In mice, the damage models used to study MMP13 and ADAMTS5 begin with a surgically unstable knee (Glasson 2005; Little 2009). Use and injury are the trigger. The cells, and enzymes such as MMP13, do the breaking down.
Tom Appleton worries about what the label does to the way people use their joints.
Wear and tear is simply not correct. And unfortunately, when people hear wear and tear, if we call it wear and tear arthritis, you've probably heard people say that before, it actually deters people from using their joints.
Other questions people ask
Is cartilage breakdown a normal part of ageing?
Not on the evidence of healthy ankle cartilage from donors aged 16 to 75, which showed no molecular signs of degeneration with age. Older cartilage cells did react more strongly to provocation in a separate study.
Does mechanical stress damage cartilage?
In rats, mechanical stress raised reactive oxygen species in cartilage cells and led to cell death and joint changes. The damage came through the cells' chemistry rather than simple abrasion.
Do these studies explain joint pain?
No. They measure cartilage, collagen and enzymes. Pain has other sources, and these papers don't test it directly.
Sources
- 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.
- 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.
- 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.
- Hu Q, Ecker M. Overview of MMP-13 as a Promising Target for the Treatment of Osteoarthritis. Int J Mol Sci 2021.
- 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.
- 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.
- Aurich M, Poole AR, Reiner A et al. Matrix homeostasis in aging normal human ankle cartilage. Arthritis Rheum 2002.
- Forsyth CB, Cole A, Murphy G et al. Increased matrix metalloproteinase-13 production with aging by human articular chondrocytes in response to catabolic stimuli. J Gerontol A Biol Sci Med Sci 2005.
- Rong J, Zhu M, Munro J et al. Altered expression of the core circadian clock component PERIOD2 contributes to osteoarthritis-like changes in chondrocyte activity. Chronobiol Int 2019.
- 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.
- Snelling SJ, Forster A, Mukherjee S et al. The chondrocyte-intrinsic circadian clock is disrupted in human osteoarthritis. Chronobiol Int 2016.
- 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.
- 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.
- Kaneko Y, Tanigawa N, Sato Y et al. Oral administration of N-acetyl cysteine prevents osteoarthritis development and progression in a rat model. Sci Rep 2019.
- Glasson SS, Askew R, Sheppard B et al. Deletion of active ADAMTS5 prevents cartilage degradation in a murine model of osteoarthritis. Nature 2005.
Read next
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...
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...
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...
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...