This 2005 study deleted the active part of ADAMTS5, the enzyme also called aggrecanase-2, in mice. After surgery made their knees unstable, these mice had significantly less cartilage destruction than normal mice. The authors called it the first single gene deletion shown to block cartilage destruction in an animal model of osteoarthritis.
Aggrecan, the proteoglycan that lets cartilage resist compression, is cut at a specific aggrecanase site in damaged human cartilage, and several ADAMTS enzymes can make that cut. To find out which one matters most, the researchers bred mice lacking the catalytic domain of ADAMTS5, surgically destabilised the knee joint, and compared cartilage destruction with that in normal (wild-type) mice.
After the surgery, the ADAMTS5 knockout mice had significantly less severe cartilage destruction than the wild-type mice. The authors concluded that ADAMTS5 is the primary aggrecanase responsible for aggrecan breakdown in this mouse model, and that this points to ways of intervening in the disease.
The abstract does not give the number of mice or how long they were followed. Mice lacking a gene from birth differ from adults whose enzyme is blocked later in life. Surgical instability in a mouse knee is a model of injury-driven damage, and mouse joints differ from human ones. The study did not look at MMP13.
It made ADAMTS5 the leading enzyme for aggrecan, as MMP13 is for type II collagen. Read alongside Little 2009, in which mice lacking MMP13 had less cartilage erosion, it shows cartilage has two main cutting enzymes for its two main components, and removing either one in mice reduced damage.
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...
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...
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...