A Broad Perspective on Chondrocyte Gene Expression

Synovial joints are composed of different tissues that function together to achieve movement with an amazingly low coefficient of friction between apposing bone surfaces. In health, joints move smoothly and painlessly with a full range of motion. Joint injuries, however, can cause inflammation and degenerative changes in multiple tissues, including the joint capsule, synovial membrane, ligaments, articular cartilage, and the bone underneath the articular cartilage. Unfortunately, not all of these tissues have good regenerative properties. Cartilage, in particular, does not heal efficiently. The cells in articular cartilage (called chondrocytes) have only a limited capacity to repair structural defects in the joint surface, which is a primary reason why osteoarthritis is a chronic and progressive disease. Lesions in the articular surface do not repair well, and joint function often deteriorates further over time.

Many scientists interested in synovial joints and osteoarthritis study the cell biology of chondrocytes. There are many important questions to investigate. How does the normal function of chondrocytes change as a horse matures? How do healthy chondrocytes respond when a horse starts into heavy work and the biomechanical stresses placed on joints increase? What variables compromise the function of chondrocytes, allowing structural lesions in articular cartilage to develop? How are chondrocyte functions altered by medications and other therapeutic interventions? Why are chondrocytes normally unable to repair a lesion in the joint surface and fully restore the structural and biomechanical integrity of articular cartilage? If and when structural lesions in the joint surface develop, what can be done to enhance the regenerative potential of chondrocytes?

An important strategy to investigate these and related questions is an analysis of chondrocyte gene expression. The basic premise is that valuable insight about cartilage can be obtained from studying changes in the pattern of chondrocyte gene expression. New technology is becoming available to make this scientific strategy much more powerful and efficient. Traditionally, gene expression has been studied one gene at a time, and scientists have been quite limited in the number of genes they could evaluate in any given experiment. With approximately 30,000 genes in the total genome, this has been an inefficient process. The new methods allow scientists to initially take a much broader perspective, screening expression across large subsets of genes in a single experiment. This capability enables informed decisions to be made subsequently on which individual genes should be most interesting to focus on at greater detail. Essentially, scientists can evaluate the “forest” before making a decision on which individual “trees” should be investigated further. To take advantage of these experimental genomic strategies, we have been working over the past two years to develop a cDNA clone set representing 9,322 different genes expressed by chondrocytes in equine articular cartilage. This clone set will enable gene expression profiling of experimental samples on a broad scale, generating data from thousands of genes not routinely studied in cartilage and more than 1,000 transcripts that do not match any functionally annotated genes. Availability of equine-specific DNA sequences is very important, because it enables our studies to be performed with specificity and sensitivity on samples isolated from horses. For scientific research on equine lameness, expression profiling of chondrocytes holds the promise of identifying both novel genes that are functionally important in cartilage and quantitative changes in gene expression that will provide valuable insight into arthritis and other joint diseases.

Dr. Jamie MacLeod, John S. and Elizabeth A. Knight Chair in Equine Musculoskeletal Sciences
(859) 257-4757, jnmacleod@uky.edu
Maxwell H. Gluck Equine Research Center. University of Kentucky.