The potential of IGF-1 and TGFbeta1 for promoting "adult" articular cartilage repair: an in vitro study.
Research into articular cartilage repair, a tissue unable to spontaneously regenerate once injured, has focused on the generation of a biomechanically functional repair tissue with the characteristics of hyaline cartilage. This study was undertaken to provide insight into how to improve ex vivo chondrocyte amplification, without cellular dedifferentiation for cell-based methods of cartilage repair. We investigated the effects of insulin-like growth factor 1 (IGF-1) and transforming growth factor beta 1 (TGFbeta1) on cell proliferation and the de novo synthesis of sulfated glycosaminoglycans and collagen in chondrocytes isolated from skeletally mature bovine articular cartilage, whilst maintaining their chondrocytic phenotype. Here we demonstrate that mature differentiated chondrocytes respond to growth factor stimulation to promote de novo synthesis of matrix macromolecules. Additionally, chondrocytes stimulated with IGF-1 or TGFbeta1 induced receptor expression. We conclude that IGF-1 and TGFbeta1 in addition to autoregulatory effects have differential effects on each other when used in combination. This may be mediated by regulation of receptor expression or endogenous factors; these findings offer further options for improving strategies for repair of cartilage defects.
Davies
Lindsay C
LC
Department of Oral Surgery, Medicine, and Pathology, School of Dentistry, Cardiff University, Heath Park, Cardiff, United Kingdom.
Blain
Emma J
EJ
Gilbert
Sophie J
SJ
Caterson
Bruce
B
Duance
Victor C
VC
D000818:Animals; D002358:Cartilage, Articular / Q000293:injuries / Q000378:metabolism* / Q000473:pathology; D002417:Cattle; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D019902:Chondrocytes / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D006025:Glycosaminoglycans / Q000096:biosynthesis; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D017526:Receptor, IGF Type 1 / Q000096:biosynthesis; D018125:Receptors, Transforming Growth Factor beta / Q000096:biosynthesis; D012038:Regeneration / Q000187:drug effects*; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*
D006025:Glycosaminoglycans; D018125:Receptors, Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1