Cotransfected human chondrocytes: over-expression of IGF-I and SOX9 enhances the synthesis of cartilage matrix components collagen-II and glycosaminoglycans

• Published in: Brazilian journal of medical and biological research Vol. 48; no. 12; pp. 1063 - 1070
• Main Authors: M. Simental-Mendía, J. Lara-Arias, E. Álvarez-Lozano, S. Said-Fernández, A. Soto-Domínguez, G. R. Padilla-Rivas, H. G. Martínez-Rodríguez
• Format: Journal Article
• Language: English
• Published: Associação Brasileira de Divulgação Científica 01.10.2015
• Subjects: Articular cartilage; Cotransfection; Glycosaminoglycans; Human chondrocytes; IGF-I/SOX9 transgenes; Type II collagen
• ISSN: 1414-431X
• DOI: 10.1590/1414-431x20154732

Damage to cartilage causes a loss of type II collagen (Col-II) and glycosaminoglycans (GAG). To restore the original cartilage architecture, cell factors that stimulate Col-II and GAG production are needed. Insulin-like growth factor I (IGF-I) and transcription factor SOX9 are essential for the synthesis of cartilage matrix, chondrocyte proliferation, and phenotype maintenance. We evaluated the combined effect of IGF-I and SOX9 transgene expression on Col-II and GAG production by cultured human articular chondrocytes. Transient transfection and cotransfection were performed using two mammalian expression plasmids (pCMV-SPORT6), one for each transgene. At day 9 post-transfection, the chondrocytes that were over-expressing IGF-I/SOX9 showed 2-fold increased mRNA expression of the Col-II gene, as well as a 57% increase in Col-II protein, whereas type I collagen expression (Col-I) was decreased by 59.3% compared with controls. The production of GAG by these cells increased significantly compared with the controls at day 9 (3.3- vs 1.8-times, an increase of almost 83%). Thus, IGF-I/SOX9 cotransfected chondrocytes may be useful for cell-based articular cartilage therapies.