Differential Regulation of Immature Articular Cartilage Compressive Moduli and Poisson’s Ratios by in vitro Stimulation With IGF-1 and TGF-β1

Gregory M. Williams, University of San Diego
Kristin J. Dills, California Polytechnic State University - San Luis Obispo
Christian R. Flores, California Polytechnic State University - San Luis Obispo
Michael E. Stender, California Polytechnic State University - San Luis Obispo
Kevin M. Stewart, California Polytechnic State University - San Luis Obispo
Lauren M. Nelson, California Polytechnic State University - San Luis Obispo
Albert C. Chen, University of San Diego
Koichi Masuda, University of San Diego
Scott J. Hazelwood, California Polytechnic State University - San Luis Obispo
Stephen M. Klisch, University of San Diego
Robert L. Sah, University of San Diego

Article comments

Copyright © 2010 Elsevier. The definitive version is available at http://dx.doi.org/10.1016/j.jbiomech.2010.05.022.

NOTE: At the time of publication, the author Steven M. Klisch was not yet affiliated with Cal Poly.

Abstract

Mechanisms of articular cartilage growth and maturation have been elucidated by studying composition-function dynamics during in vivo development and in vitro culture with stimuli such as insulin-like growth factor-1 (IGF-1) and transforming growth factor-beta 1 (TGF-β1). This study tested the hypothesis that IGF-1 and TGF-β1 regulate immature cartilage compressive moduli and Poisson’s ratios in a manner consistent with known effects on tensile properties. Bovine calf articular cartilage from superficial-articular (S) and middle-growth (M) regions were analyzed fresh or following culture in medium with IGF-1 or TGF-β1. Mechanical properties in confined (CC) and unconfined (UCC) compression, cartilage matrix composition, and explant size were assessed. Culture with IGF-1 resulted in softening in CC and UCC, increased Poisson’s ratios, substantially increased tissue volume, and accumulation of glycosaminoglycan (GAG) and collagen (COL). Culture with TGF-β1 promoted maturational changes in the S layer, including stiffening in CC and UCC and increased concentrations of GAG, COL, and pyridinoline crosslinks (PYR), but little growth. Culture of M layer explants with TGF-β1 was nearly homeostatic. Across treatment groups, compressive moduli in CC and UCC were positively related to GAG, COL, and PYR concentrations, while Poisson’s ratios were negatively related to concentrations of these matrix components. Thus, IGF-1 and TGF-β1 differentially regulate the compressive mechanical properties and size of immature articular cartilage in vitro. Prescribing tissue growth, maturation, or homeostasis by controlling the in vitro biochemical environment with such growth factors may have applications in cartilage repair and tissue engineering.