Conclusion
ASC CM-derived TGF-beta1-induced chondrogenic differentiation of ASCs resulted in significant reduction in chondrogenic activity after inhibition of the p38 pathway, revealing involvement of this MAPK pathway in TGF-beta1 signalling. On the other hand, TGF-beta1 signalling also led to SMAD activation that could directly increase chondrogenic activity of ASCs.
Results
Of these proteins, 33 were identified as chondrogenic factors or proteins including type 2 collagen, biglycan, insulin-like growth factor-binding protein and transforming growth factor-beta 1 (TGF-beta1). ASCs are a possible cell source for cartilage regeneration as they are able to secrete a number of functional cytokines including chondrogenesis-inducing molecules such as TGF-beta1 and bone morphogenetic protein 4 (BMP4). The chondrogenic phenotype of cultured ASCs was effectively induced by ASC-culture media (CM) containing BMP4 and TGF-beta1, and maintained after pre-treatment for 14 days in vitro and subcutaneous implantation in vivo. Chondrogenic differentiation efficiency of cultured ASCs and cultured mouse skin-derived progenitor cells (SPCs) depended absolutely on ASC CM-fold concentration. Cell density was also a very important factor for chondrogenic behaviour development during differentiation of ASCs and SPCs.