Chondrocytes Differentiation Of Bone Marrow-derived Mesenchymal Stem Cells Induced By HDAC Inhibitor In Vitro

In cartilage tissue engineering, the treatment for cartilage diseases is primarily palliative cause adult cartilage tissue has poor capability of self-repairing and regeneration, which has led to efforts to develop alternative means to supply sufficient chondrocytes.Bone marrow-derived mesenchymal stem cells (MSCs) have been shown to differentiate into distinct mesenchymal tissues including bone and cartilage. The capacity of MSCs to replicate undifferentiated and to differentiate into cartilaginous tissues suggests these cells as an attractive cell source for cartilage tissue engineering. Vaproic acid (VPA), as an typical histone deacetylase (HDAC) inhibitor, has been identified the potential of inducing MSCs differentiation into hepatocytes, neurocytes as well as osteoblasts. However, none has been reported about related studies on chondrocytes differentiation till now. Here we showed that the stimulation of murine bone marrow-derived MSCs with Vaproic acid sodium (VPA) resulted in chondrogenic lineage development under serum-free conditions. Detection on the morphous, protein and gene levels suggested that MSCs are able to differentiate into homogeneous chondrocyte-like cells which have the ability of depositing the cartilage-specific type II collagen as well as proteoglycan. It has also been compared of the VPA to basic fibrolast growth factor (FGF-2) on the efficacy of MSCs chondrocyte differentiation. Results showed that VPA plays a similar effect on the inducing process with FGF-2, while the combination of VPA and FGF-2 leads to cell apoptosis. The fact that FGF-2 is an important growth factor on chondrocyte differentiation reminds us that VPA may completes the inducing procedure by exposuring the transcription factor binding sites of FGF-2 by modifying chromosome structures. Using flow cytometer (FCM), it was showed that the cell cycle of a large proportion of cells induced for 6 days was blocked in the G0-G1 stage, meanwhile, mRNA of CollagenII achieved a high level, which suggested that the MSCs have exited the proliferation cycle and differentiated actively. The present study reveals the latent capacity of VPA as a single inducer on the MSCs chondrocyte differentiation. Therefore, MSCs stimulated with VPA may serve as a valuable source of easily accessible mesenchymal progenitor cells for the evolving field of tissue engineering to regenerate cartilage autologously.