Principal Investigator: R. Lane Smith, PhD Co-Investigator: Gary S. Beaupré, PhD Collaborators: Nicholas J. Giori, MD, PhD; John C. Zauner, MD; and Christopher R. Jacobs, PhD Project Category: Arthritis - 2005 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 and long-term health status. Current treatment methods are limited to surgical approaches that require the transfer of good cartilage from one site on the joint surface to an area with cartilage degradation. This goal of this research is to establish a way to repair OA cartilage that will avoid transfer of good cartilage by regeneration of damaged cartilage in situ. The mechanical loading environment within diarthrodial joints is critical for the normal homeostasis of the articular cartilage load-bearing extracellular matrix. The matrix is produced by the articular chondrocytes in the tissue, which are responsive to the mechanical loads applied during daily activity. The work proposed here addresses the hypothesis that activation articular cartilage matrix gene expression requires optimal 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 under precisely defined loading conditions in the presence and absence of the growth factor, bone morphogenetic 2 (BMP-2), serves as stimulus for articular cartilage repair and regeneration in osteoarthritis. The experiments test the effect of applying intermittent hydrostatic pressure on human osteoarthritic cartilage explants with and without BMP-2 on expression of the large aggregating proteoglycans, aggrecans and type II collagen. In addition, the experiments will examine the differences in the effect of loading with and without BMP-2 on expression of the cartilage matrix between normal and osteoarthritic cartilage. Milestones:
Funding Source: VA RR&D Merit Review Funding Status: Active
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