OBJECTIVES: This article addresses the interaction of transforming growth factor beta1 (TGF-beta1) and bone morphogenic protein 2 (BMP-2) during osteo-chondrogenic differentiation of adipose-derived adult stem cells (ASC). TGF-beta1 was expected to modulate the BMP-2-induced effects through transcriptional regulation of Dlx-5, Msx-2 and Runx-2.
MATERIALS AND METHODS: Encapsulated ASC were cultured for 14 days in medium containing TGF-beta1 and/or BMP-2. mRNA expression of the extracellular matrix molecules col2a1, cartilage oligomeric matrix protein, col10a1, alkaline phosphatase (AP) and transcription factors Msx-2, Dlx-5 and Runx-2 was analysed. Release of glycosaminoglycans, collagen types II and X into the extracellular matrix was demonstrated.
RESULTS: BMP-2 and TGF-beta1 induced a chondrogenic phenotype in ASC. Combined growth factor treatment had a synergistic effect on col10a1 and an additive effect on col2a1 mRNA expression. Synthesis of glycosaminoglycans was enhanced by combined growth factor treatment. Addition of TGF-beta1 inhibited BMP-2 induced AP expression and activity and both proteins promoted chondrogenic maturation.
CONCLUSIONS: Prevention of BMP-2-induced osteogenic transdifferentiation by TGF-beta1 seemed not to be mediated by transcriptional regulation of Dlx-5. Due to these findings, simultaneous stimulation of ASC with BMP-2 and TGF-beta1 seemed to be beneficial for complete differentiation of ASC into chondrocytes.