title: Differential regulation of immature articular cartilage compressive moduli and Poisson's ratios by in vitro stimulation with IGF-1 and TGF-beta1.
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-beta1). This study tested the hypothesis that IGF-1 and TGF-beta1 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-beta1. 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-beta1 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-beta1 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-beta1 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.
authors.affiliation: Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093-0412, USA.
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Williams
authors.forename: Kristin J
authors.initials: KJ
authors.lastname: Dills
authors.forename: Christian R
authors.initials: CR
authors.lastname: Flores
authors.forename: Michael E
authors.initials: ME
authors.lastname: Stender
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Stewart
authors.forename: Lauren M
authors.initials: LM
authors.lastname: Nelson
authors.forename: Albert C
authors.initials: AC
authors.lastname: Chen
authors.forename: Koichi
authors.initials: K
authors.lastname: Masuda
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Hazelwood
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Klisch
authors.forename: Robert L
authors.initials: RL
authors.lastname: Sah
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D002358:Cartilage, Articular / Q000187:drug effects* / Q000254:growth & development / Q000502:physiology; D002417:Cattle; D003094:Collagen / Q000378:metabolism; D019245:Compressive Strength; D006025:Glycosaminoglycans / Q000378:metabolism; D006706:Homeostasis; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D013718:Tensile Strength / Q000502:physiology; D046509:Tissue Culture Techniques; D023822:Tissue Engineering; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*
chemical_list: D006025:Glycosaminoglycans; D053773:Transforming Growth Factor beta1; D007334:Insulin-Like Growth Factor I; D003094:Collagen