Biochemical and functional modulation of the cartilage collagen network by IGF1, TGFβ2 and FGF2

Objective: Examine effects of insulin-like growth factor 1 (IGF1), transforming growth factor beta 2 (TGF beta 2) and fibroblast growth factor 2 (FGF2) on proteoglycan and collagen network and biomechanical properties of the newly formed cartilage matrix. Methods: Bovine articular chondrocytes were cultured in alginate beads for 3 weeks with or without FGF2, TGF beta 2 or IGF1 in the presence of 10% FCS. Proteoglycan content, collagen content, hydroxylysylpyridinoline cross-links and overall matrix metalloproteinase (MMP) activity in the culture medium were measured. Alginate disks cultured for 5 weeks were used to evaluate the effect of growth factors on mechanical properties of the construct by determining the equilibrium aggregate modulus and secant modulus. Results: IGF1 increased collagen and proteoglycan deposition. FGF2 mainly decreased collagen deposition and TGF beta 2 proteoglycan deposition. A decrease in cross-links was observed in matrix produced by chondrocytes cultured in the presence of TGF beta 2. IGF1 and FGF2 had no influence on the number of cross-links per collagen molecule. Overall MMP activity was significantly higher in culture medium of cells cultured with FGF2. TGF beta 2 and IGF1 had no effect on MMP activity. After 35 days of culture, the matrix produced under influence of IGF1 had a lower permeability and a trend to increase stiffness. FGF2 showed a trend to lower both properties. TGF beta 2 had no effect on these parameters. Conclusion: IGF1, TGF beta 2 and FGF2 had differential effects on collagen network formation. Of the three growth factors tested, IGF1 seems to be best in promoting the formation of a functional collagen network since it increased proteoglycan and collagen deposition and improved the mechanical properties. (C) 2006 OsteoArthritis Research Society International. Published by Elsevier Ltd. All rights reserved.