This 2010 review describes the tissue inhibitors of metalloproteinases (TIMPs). Humans carry four TIMP genes. TIMPs were first known as MMP inhibitors but also block several ADAM and ADAMTS enzymes, so they regulate the enzymes that break down the extracellular matrix. They also have effects that do not depend on blocking enzymes.
This is a review of published research, not a new experiment. The authors summarised what was known about the TIMP family: its spread across the animal kingdom, the structures of TIMPs locked onto their target enzymes, efforts to engineer TIMP variants that block selected enzymes, activities that have nothing to do with blocking enzymes, and findings from mice with TIMP genes deleted.
TIMPs are widely distributed in the animal kingdom, and the human genome has four genes, for TIMP-1 to TIMP-4. They inhibit MMPs and several ADAMs and ADAMTSs, so they regulate the enzymes that degrade the extracellular matrix and shed molecules from cell surfaces. Structural studies show TIMPs bind their targets at several sites, which has let researchers make variants that block selected groups of enzymes, though changes in the TIMP's flexibility on binding complicate this. TIMPs also affect cell growth and differentiation, cell migration, blood vessel growth, cell death and synaptic plasticity. Mice with specific TIMP genes deleted have shown their importance in health and disease.
A review adds no new data. The abstract does not single out MMP13 or cartilage, and it does not say which TIMP matters most in joints. It describes how TIMPs work in general, not whether raising them would protect cartilage in people.
MMP13 is not left to run unchecked. The TIMPs are the body's own brakes on it and its relatives, and Knäuper's 1996 study showed TIMP-1, TIMP-2 and TIMP-3 each block MMP13 one to one. Some of the plant-compound studies on this site report a rise in TIMP-1, which only makes sense once you know what TIMPs do.
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...
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...