If DNA is the “source code” for our bodies, then the end product—the stuff that makes our bodies work—are the proteins. Only recently has it become possible to study proteins on a grand scale, thanks to the development of fantastic databases, the sequencing of the genome, computers, and a special device called a mass spectrometer. The first problem to consider is that there are thought to be 30-40,000 genes, but there are ten times as many proteins. This means that DNA sequencing alone does not “explain” everything, that the proteins are somehow modified to reflect specialized function. This is the realm of post translational modification, which is where mass spectrometry excels.

Fortunately, compared with most tissues, cartilage does not have many proteins. Cartilage is composed of a small volume of cells that secrete proteins into the matrix, or gel; thxxe gel attracts water, and it is this firm but elastic, acellular material that moves our joints and bears our weight. If the gel cracks and splits, it will eventually delaminate and we lose the cushion upon which we walk. Arthritis (osteoarthritis) is the condition named for deterioration of the joint that is visible, on radiographs, by the loss of this cushion. Radiographs do not image the cartilage directly.

So cartilage provides a good model for studying a relatively small number of (important) proteins with a specific function. I have collaborated with the proteomics group at the University of Virginia, Dr. Ben Garcia and Dr. Don Hunt, in applying this technology. We have found, first of all, that the study of very, very small amounts of protein is possible by this method, and the specific proteins can be identified accurately. Secondly, there are approximately 100 proteins, some of very small abundance, in cartilage, and many of these have not before been recognized. Our studies will hopefully lay a foundation to examine these proteins in health and disease. Future treatments aimed at reversing cartilage disease will ultimately be proven by methods such as this—and the results will be measurable.

Protein Profile of osetoarthritic human articular cartilage using tandem mass spectrometry. Garcia, B, Platt, M Born, T. Shabanowitz, J Marcus N.A. & Hunt, D.F./ RAPID COMMUNICATIONS IN MASS SPECTROMETRY 2006, 20; 1-8.