%0 Journal Article
%T Progression of Gene Expression Changes following a Mechanical Injury to Articular Cartilage as a Model of Early Stage Osteoarthritis
%A R. S. McCulloch
%A M. S. Ashwell
%A C. Maltecca
%A A. T. O'Nan
%A P. L. Mente
%J Arthritis
%D 2014
%I Hindawi Publishing Corporation
%R 10.1155/2014/371426
%X An impact injury model of early stage osteoarthritis (OA) progression was developed using a mechanical insult to an articular cartilage surface to evaluate differential gene expression changes over time and treatment. Porcine patellae with intact cartilage surfaces were randomized to one of three treatments: nonimpacted control, axial impaction (2000£¿N), or a shear impaction (500£¿N axial, with tangential displacement to induce shear forces). After impact, the patellae were returned to culture for 0, 3, 7, or 14 days. At the appropriate time point, RNA was extracted from full-thickness cartilage slices at the impact site. Quantitative real-time PCR was used to evaluate differential gene expression for 18 OA related genes from four categories: cartilage matrix, degradative enzymes and inhibitors, inflammatory response and signaling, and cell apoptosis. The shear impacted specimens were compared to the axial impacted specimens and showed that shear specimens more highly expressed type I collagen (Col1a1) at the early time points. In addition, there was generally elevated expression of degradative enzymes, inflammatory response genes, and apoptosis markers at the early time points. These changes suggest that the more physiologically relevant shear loading may initially be more damaging to the cartilage and induces more repair efforts after loading. 1. Introduction Osteoarthritis is estimated to affect 27 million Americans and this number is predicted to rise over the coming years [1]. While the causes and progression of OA are not completely understood, a prior joint injury is a known predisposing factor for the development of OA [2]. Therefore, in a laboratory setting, an injury model may be used to study the early stage progression of cartilage degeneration. One common method of modeling OA in a laboratory setting is that of an impact injury. In this scenario, a controlled impact is delivered to the joint surface and induced changes are evaluated. The impacts can be done in vivo [3¨C5] or in vitro [6¨C9]. However, an in vivo impact injury may prove difficult to evaluate in terms of ongoing loading following the discrete loading event. Thus, an in vitro model allows for much more accurate quantification of the mechanical forces delivered to the articular surface. Most impact studies have utilized loading normal to the cartilage surface [3, 5¨C11]; however a real physiologic loading event likely has loading along multiple axes. Therefore one of our aims was to employ a more complex impact model with elevated shear loading. Identifying differences in gene
%U http://www.hindawi.com/journals/arthritis/2014/371426/