Browsing by Subject "growth factor"

Now showing 1 - 3 of 3
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    Customized biomaterials to augment chondrocyte gene therapy
    (Elsevier, 2017-04) Aguilar, Izath Nizeet; Trippel, Stephen; Shi, Shuiliang; Bonassar, Lawrence J.; Orthopaedic Surgery, School of Medicine
    A persistent challenge in enhancing gene therapy is the transient availability of the target gene product. This is particularly true in tissue engineering applications. The transient exposure of cells to the product could be insufficient to promote tissue regeneration. Here we report the development of a new material engineered to have a high affinity for a therapeutic gene product. We focus on insulin-like growth factor-I (IGF-I) for its highly anabolic effects on many tissues such as spinal cord, heart, brain and cartilage. One of the ways that tissues store IGF-I is through a group of insulin like growth factor binding proteins (IGFBPs), such as IGFBP-5. We grafted the IGF-I binding peptide sequence from IGFBP-5 onto alginate in order to retain the endogenous IGF-I produced by transfected chondrocytes. This novel material bound IGF-I and released the growth factor for at least 30 days in culture. We found that this binding enhanced the biosynthesis of transfected cells up to 19-fold. These data demonstrate the coordinated engineering of cell behavior and material chemistry to greatly enhance extracellular matrix synthesis and tissue assembly, and can serve as a template for the enhanced performance of other therapeutic proteins.
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    Osteoglophonic dysplasia: A ‘common’ mutation in a rare disease
    (Wiley Online Library, 2010-08) Sow, AJ; Ramli, R.; Latiff, ZA; Ichikawa, S.; Gray, AK; Nordin, R.; Abd Jabar, MN; Primuharsa Putra, SHA; Siar, CH; Econs, MJ; Department of Medicine, IU School of Medicine
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    Regulation of articular chondrocyte catabolic genes by growth factor interaction
    (Wiley, 2019-02-27) Shi, Shuiliang; Mercer, Scott; Eckert, George J.; Trippel, Stephen B.; Orthopaedic Surgery, School of Medicine
    Osteoarthritis is characterized by a loss of articular cartilage homeostasis in which degradation exceeds formation. Several growth factors have been shown to promote cartilage formation by augmenting articular chondrocyte anabolic activity. This study tests the hypothesis that such growth factors also play an anti-catabolic role. We transferred individual or combinations of the genes encoding insulin- like growth factor I, bone morphogenetic protein-2, bone morphogenetic protein-7, transforming growth factor-β1 and fibroblast growth factor-2, into adult bovine articular chondrocytes and measured the expression of catabolic marker genes encoding A disintegrin and metalloproteinase with thrombospondin motifs-4 and −5, matrix metalloproteinases-3 and −13, and interleukin-6. When delivered individually, or in combination, these growth factor transgenes differentially regulated the direction, magnitude and time course of expression of the catabolic marker genes. In concert, the growth factor transgenes regulated the marker genes in an interactive fashion that ranged from synergistic inhibition to synergistic stimulation. Synergistic stimulation prevailed over synergistic inhibition, reaching maxima of 15.2-fold and 2.7-fold, respectively. Neither the magnitude nor the time course of the effect of the transgene combinations could be predicted on the basis of the individual transgene effects. With few exceptions, the data contradict our hypothesis. The results demonstrate that growth factors that are traditionally viewed as chondrogenic tend also to promote catabolic gene expression. The competing actions of these potential therapeutic agents add an additional level of complexity to the selection of regulatory factors for restoring articular cartilage homeostasis or promoting repair.