Friday, February 23, 1996
In recent years new knowledge of cartilage and bone at the molecular level has improved the understanding of mechanisms in tissue breakdown and repair. The study of altered synthesis and breakdown of matrix molecules provides important information on mechanisms in diseases which affect joint structures. This year's Steindler Lecturer, Dick Heinegard, MD, Lund, Sweden, discussed some of these issues in his presentation "Molecular Functions and Events in Joint Tissue with Implication for the Management of Disease."
Dr. Heinegard focused on osteoarthritis (OA) and how new developments may help physicians diagnose and begin treating the condition at an earlier stage. "This disease is usually not diagnosed until it has reached the end stages, at which point there is no truly disease-modifying therapy we can employ," Dr. Heinegard said. "So, we must find a way to identify the disease early and introduce therapy to prevent or stop the development of clinical osteoarthritis." This will require new diagnostic approaches that depend on improved understanding of underlying mechanisms, he added.
When looking at tissue loss, there is usually a balance between degradation and new synthesis. In OA, however, there is an obvious imbalance between breakdown and synthesis. "Not all loss of substance is permanent or destructive," Dr. Heinegard said, pointing out the facts that proteoglycans are lost upon immobilization and that acute reactive arthritis occurs without permanent or chronic disease. "The early events affect the matrix of cartilage and bone. Therefore we must study the composition of the matrix and functions of their components," he said. "These components include the collagen network and proteoglycans."
More than 95 percent of proteoglycans in cartilage is aggrecan, Dr. Heinegard said. This includes about 100 chrodoitin sulfate chains with 80-100 negatively charged groups fixed to core protein at one end; many aggrecan molecules can be found fixed to hyaluronan.
Some components that are part of the collagen network include Collagen IX, Decorin, Fibromodulin, Lumican, Fibronectin, and CMP (not in articular cartilage). "We see collagen fibers of limited length, and in order to optimize the tensile properties of the fibrillar network, fibers are 'glued' together," said Dr. Heinegard. "An early sign of OA is that we start to see surface fibrillation of the articular cartilage."
Some of the other alterations observed in early OA include the increased synthesis of COMP, 92 kDa, 39 kDa, and Fibronectin proteins. "These may be markers in the early diagnosis of this disease," he said.
Results of recent studies have led Dr. Heinegard and other researchers to several conclusions:
Increasing s-COMP and s-BSP most likely reflect increased cartilage and bone matrix turnover and appear to be of prognostic significance in OA of the knee joint.
Signs of episodic progression can be found in the cartilage as well as in the subchondral bone; changes in s-COMP and s-BSP appear to reflect events that are not directly related.
Increased levels of s-COMP in early RA predicts aggressive disease.
Dr. Heinegard hopes that future developments will lead to the identification of the character of the fragments released and that the cleavage site may help to define proteinase-inhibitors. "Hopefully, specific diagnoses may be ascertained from studying the cleavage pattern," said Dr. Heinegard. Detailed knowledge of events in the joint tissues at the molecular level will allow the development of new diagnostic procedures and provide a basis for new avenues of therapeutic intervention.
||1996 Academy News Index|
Last modified 27/September/1996