Osteoarthritis

Pathology

See also: Synovial Joints, Fibrous Connective Tissues

The extracellular matrix of cartilage is made up of two main macromolecules: type II collagen and aggrecan. Aggrecan is a large aggregating proteoglycan which retains water. The type II collagen provides intrinsic resistance to tension, and allows the proteoglycans to swell against it to provide resistance to compression. There are other more minor components that also play a role in matrix structure such as other forms of collagen (e.g. types IX, XI, and VI collagen), proteoglycans (e.g. biglycan, decorin), and cartilage oligomerix matrix protein.

In the normal state there is an equilibrium between synthesis and degradation of the extracellular matrix. Degradation allows for clearing of old components so that fresh components can be synthesised. In osteoarthritis there is a disruption of this balance so that the degradative processes are favoured, leading to cartilage destruction.

The classic degradative enzymes, produced in the chondrocyte and synovium, are the metalloproteinases (MMPs) which facilitate the turnover of the extracellular matrix in both normal and osteoarthritic states. It is thought that MMP-1 is the primary collagenase in rheumatoid arthritis, and MMP-13 is the primary collagenase in osteoarthritis.

The A Disintegrin And Metalloproteinase with Thrombospondin Motifs (ADAMTS) group of proteinases were discovered later and are involved in both the synthesis and degradation of the extracellular matrix. ADAMTS enzymes include the procollagen propeptidases that are involved in collagen biosynthesis, and the aggrecanases that are involved in aggrecan degradation.

There are also important inhibitors, and the tissue inhibitors of metalloproteinases (TIMPs) are able to inhibit the activity of MMPs and potentially ADAMTS. In osteoarthritis there can be an imbalance between metalloproteinase and TIMP activities.