Differential effects of BMP-2 and TGF-β1 on chondrogenic differentiation of adipose derived stem cells

Objectives : This article addresses the interaction of transforming growth factor beta 1 ( TGF- beta 1) and bone morphogenic protein 2 ( BMP- 2) during osteo- chondrogenic differentiation of adipose- derived adult stem cells ( ASC). TGF- beta 1 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- beta 1 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- beta 1 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- beta 1 inhibited BMP- 2 induced AP expression and activity and both proteins promoted chondrogenic maturation. Conclusions : Prevention of BMP- 2- induced osteogenic transdifferentiation by TGF- beta 1 seemed not to be mediated by transcriptional regulation of Dlx- 5. Due to these findings, simultaneous stimulation of ASC with BMP- 2 and TGF- beta 1 seemed to be beneficial for complete differentiation of ASC into chondrocytes.