Tumor necrosis factor-a inhibition restores matrix formation by human adipose-derived stem cells in the late stage of chondrogenic differentiation

摘要

BACKGROUND Cartilage tissue engineering is a promising strategy for treating cartilage damage. Matrix formation by adipose-derived stem cells (ADSCs), which are one type of seed cell used for cartilage tissue engineering, decreases in the late stage of induced chondrogenic differentiation in vitro, which seriously limits research on ADSCs and their application. AIM To improve the chondrogenic differentiation efficiency of ADSCs in vitro, and optimize the existing chondrogenic induction protocol. METHODS Tumor necrosis factor-alpha (TNF-alpha) inhibitor was added to chondrogenic culture medium, and then Western blotting, enzyme linked immunosorbent assay, immunofluorescence and toluidine blue staining were used to detect the cartilage matrix secretion and the expression of key proteins of nuclear factor kappa-B (NF-kappa B) signaling pathway. RESULTS In this study, we found that the levels of TNF-alpha and matrix metalloproteinase 3 were increased during the chondrogenic differentiation of ADSCs. TNF-alpha then bound to its receptor and activated the NF-kappa B pathway, leading to a decrease in cartilage matrix synthesis and secretion. Blocking TNF-alpha with its inhibitors etanercept (1 mu g/mL) or infliximab (10 mu g/mL) significantly restored matrix formation. CONCLUSION Therefore, this study developed a combination of ADSC therapy and targeted anti-inflammatory drugs to optimize the chondrogenesis of ADSCs, and this approach could be very beneficial for translating ADSC-based approaches to treat cartilage damage.

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