Principal Investigator: R. Lane Smith, PhD Project Staff: Gary S. Beaupré, PhD; Dennis R. Carter, PhD; Andrew R. Hoffman, MD; George Sims, MD; John Zauner, MD; Stuart B. Goodman, MD, PhD; and David J. Schurman, MD Project Category: Arthritis - 2004 Articular cartilage destruction in osteoarthritis (OA) is induced by alterations in the mechanical loading of cartilage and changes in cartilage cell metabolism. Loss of load bearing properties of the cartilage extracellular matrix culminates in loss of joint function. Changes in chondrocyte gene expression leads to a matrix that undergoes a progressive loss of integrity with continued loading of the joint during activities of daily living. The loss of joint function results in severe impairment of daily activity and is a major clinical problem that seriously impacts personal productivity, long-term health and general well-being. Physiological levels of intermittent hydrostatic pressure applied to the chondrocytes is an important determinant in maintaining normal diarthrodial joint function. The work proposed here addresses the hypothesis that activation articular cartilage matrix gene expression requires exposure to intermittent hydrostatic pressure. The specific hypothesis to be tested is that intermittent hydrostatic pressure serves as a critical stimulus for normal cartilage extracellular matrix synthesis and deposition. This study will investigate how intermittent hydrostatic pressure applied over precisely defined loading periods serves as a stimulus for articular cartilage repair and regeneration. The experiments test effects of applying intermittent hydrostatic pressure on human osteoarthritic cartilage cells to: (1) induce expression of the large aggregating proteoglycans, aggrecans and type II collagen; (2) decrease expression of the matrix metalloproteinases; and (3) act in concert with the effects of serum-derived and purified growth factors. Milestones: Publication documenting effects of intermittent hydrostatic pressure on suppression of cartilage matrix metalloproteinase and inflammatory cytokine and chemokine expression. Presentation at the Combined Meeting of the Orthopaedic Research Society documenting effects of bone morphogenetic protein-2 (BMP-2)and intermittent hydrostatic pressure on cartilage matrix protein expression in OA chondrocytes. Funding Source: VA RR&D Merit Review Funding Status: Active |
