title: Transport of tissue inhibitor of metalloproteinases-1 through cartilage: contributions of fluid flow and electrical migration.
abstract: The preservation of the structure of articular cartilage depends on the availability of inhibitors of matrix-degrading enzymes. Tissue inhibitor of metalloproteinases-1 is thought to be an important contributor to the integrity of the matrix of articular cartilage, but the mechanisms that regulate its availability within the tissue are poorly understood. These studies elucidate the contributions of diffusion, fluid flow, and electrical migration to the transport of iodinated recombinant human tissue inhibitor of metalloproteinases-1 through explants of adult bovine articular cartilage under conditions relevant to the loading of cartilage. With use of measured partition coefficients of the cartilage explants, the diffusivity of the inhibitor was 0.5-1.6 x 10(-7) cm2/sec. Fluid velocities that were induced by applying an electrical current across the cartilage disks increased the flux of the inhibitor by approximately 20 to more than 150-fold compared with the effect of diffusion alone for the range of current densities that were applied. We examined the contribution of electrophoretic migration by titrating the charge on the inhibitor during measurements of flux and found that flux in the presence of the applied current decreased as the inhibitor became more negatively charged. Enhancements in the flux of the inhibitor were observed relative to the flux during diffusion alone even under conditions in which electrophoretic migration opposed the flux due to fluid flow, suggesting that of the transport mechanisms tested, fluid flow was dominant. These results suggest that the physical phenomena present during physiologic loading conditions (e.g., fluid flows and streaming currents) can affect the transport of tissue inhibitor of metalloproteinases-1 through the matrix of cartilage.
authors.affiliation: Center for Biomedical Engineering and Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, USA.
authors.forename: A M
authors.initials: AM
authors.lastname: Garcia
authors.forename: M W
authors.initials: MW
authors.lastname: Lark
authors.forename: S B
authors.initials: SB
authors.lastname: Trippel
authors.forename: A J
authors.initials: AJ
authors.lastname: Grodzinsky
mesh_terms: D000818:Animals; D001692:Biological Transport; D002358:Cartilage, Articular / Q000378:metabolism*; D002417:Cattle; D004058:Diffusion; D006801:Humans; D011994:Recombinant Proteins / Q000493:pharmacokinetics; D012995:Solubility; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000493:pharmacokinetics*
chemical_list: D011994:Recombinant Proteins; D019715:Tissue Inhibitor of Metalloproteinase-1