Graduate Student Dan Mittelstaedt Publishes in Cartilage


Graduate Student Dan Mittelstaedt Publishes in Cartilage 

Medical Physics graduate student Dan Mittelstaedt published a paper in the October 2015 issue of the journal Cartilage (Volume 6, Pages 216-225) about the depth-dependent glycosaminoglycan concentration in articular cartilage by quantitative contrast-enhanced micro-computed tomography. Mittelstaedt works with CBR member Yang Xia, of the Department of Physics. Xia’s research is supported by grant R01AR052353 from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, one of the National Institutes of Health. 

Below are excerpts from the introduction of the paper. 

Articular cartilage is comprised of an extracellular matrix (ECM) primarily composed of water, collagen fibers, and proteoglycans (PG) composed of negatively charged glycosaminoglycans (GAG). The interaction between these macromolecules creates a hydraulic permeability allowing diffusion from the synovial fluid to obtain nutrients essential to maintaining integrity of the tissue. The collagen fibers are oriented depth-dependently into 3 subtissue zones with respect to the surface defined as: parallel (superficial zone [SZ]), random (transitional zone [TZ]), and perpendicular (radial zone [RZ]). The collagen fibers in the ECM are intertwined with PG molecules depth-dependently in different concentrations. PG macromolecules are composed of a protein core composed of highly electronegative side chains, chondroitin and keratan sulfate, and hyaluronan, which binds aggrecan monomers to form highly charged aggregates that help regulate the diffusion of solutes attributed to the hydrophilic fixed charge density (FCD) and contributes to pore size with a link protein. Reduced GAG concentration, either natural or contrived, exhibits both an increased diffusion rate and increased equilibrium concentration of an anion due to the reduced FCD. Reduction of GAG alters the collagen fiber structural integrity and has been associated with the initial degradation and/or onset of diseases (e.g., osteoarthritis [OA]) and quantitative depth-dependent measurements may aid in diagnosing and treating nonhealthy cartilage…. 

The aim of the present study was to quantify and compare of the depth and zonal dependencies of the GAG concentration of native and degraded ex vivo articular cartilage using quantitative contrast enhanced micro–computed tomography (qCECT) at high resolution.