Mice made to produce active MMP13 in their cartilage developed cartilage erosion

What they did

The team built transgenic mice carrying a constitutively active human MMP13, a version that is always switched on. A cartilage-specific promoter limited it to the cartilage and joints, and a tetracycline control let the researchers switch the gene on after birth. They then examined the mice's joints for changes.

What they found

Once the gene was switched on, the mice's articular cartilage showed changes similar to those seen in human joint disease. These included the characteristic erosion of the cartilage, loss of proteoglycan, excessive cleavage of type II collagen by collagenase, and synovial hyperplasia, an overgrowth of the joint lining. The authors concluded that excessive MMP13 activity can result in cartilage breakdown and joint changes of this kind.

What it can't tell us

These mice made a permanently active enzyme at levels set by the experiment, which is not how MMP13 behaves in a normal joint. The abstract does not say how many mice were studied or for how long. It shows MMP13 can cause this damage, not that it is the cause in any particular person.

Why it matters

Finding more MMP13 in damaged cartilage could mean the enzyme causes damage, or simply follows it. This study tested cause directly. Turning on active MMP13 in otherwise normal mouse cartilage was enough to produce erosion and excess type II collagen cleavage.

The paper

1. 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/JCI10564

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