Physiology and Biochemistrypgpic

It was originally thought that due to the avascularity of cartilage, low oxygen consumption and poor healing, that cartilage is essentially metabolically inert. However work on the uptake of labelled sulphate complexes into cartilage in the 1960’s and 70’s demonstrated clearly that adult cartilage is constantly turning over. This turnover however is not uniform and some areas have high turnover while others have lower turnover. Additionally it would seem that proteoglycan turnover is faster than collagen turnover. Consequently it became clear that cartilage cells are actually quite active metabolically and are more or less constantly producing cartilage matrix.

Extracellular matrix consists of framework of collagen, glycosaminoglycans (GAG), and proteoglycans (PG) in a ground substance composed mainly of water. Water makes up 79-80% of articular cartilage with collagen making up 10% and GAGs and PGs 10%. Collagen fibrils are made principally of Type 2 collagen along with Type XI collagen. Hyaluronic acid is the only GAG in cartilage not bound to a protein to form a proteoglycan molecule. Proteoglycans consist of a backbone of protein with side chains of the GAGs Chondroitin Sulfate and Keratan Sulfate. The GAGs are chains of sugars with negative charges that repel each other leading to a "bottlebrush" structure of the proteoglycan. Due to it’s polar nature, water is drawn to the molecule and held loosely there. (picture of proteoglycan).

Cartilage matrix breakdown is principally under the action of collagenase, hyaluronidase, matrix metalloproteinases (MMP’s), and aggrecanase. These enzymes are produced both by the chondrocytes in the articular cartilage and also by the synovial cells.

Normal regulation of cartilage metabolism is influenced by a variety of factors including endocrine (insulin like growth factors, transforming growth factor beta, fibroblast growth factor), autocrine (various interleukins) and local tissue environment (pH, O2 tension, protein breakdown products). There are so many interactions and positive and negative feedback controls that it is almost impossible to produce a model that in any way reflects the complexity of interactions. Many diseases of the joint are caused by derangement in one or more of these control mechanisms.