生长因子可诱导干细胞成软骨分化，但是常用的转化生长因子（Transforming growth factor β1, TGF-β1）价格昂贵、半衰期短，且容易引起功能异质性，不利于临床应用。我们的前期研究发现了从眼镜蛇毒中提取的天然活性蛋白—神经生长因子（NGF）具有特异性成软骨诱导作用，且效果相比于TGF-β1更为显著。进一步研究其分子生物学机制，基于RNA-Seq、生物信息学分析及实验验证，预测蛇毒NGF可能通过抑制PHLPP1激活TNF信号通路上调sox9表达，从而诱导骨髓间充质干细胞（BMSCs）成软骨分化。为进一步证实此假说，本项目将研究PHLPP1及TNF信号通路在NGF诱导软骨形成中的作用及机制研究，以及对软骨生成的影响，阐明蛇毒NGF成软骨分化机理，为软骨诱导生长因子的优化设计奠定理论基础。

Growth factors can induce chondrogenic differentiation of stem cells. The commonly used transforming growth factor (TGF-β1) falls short in meeting the needs of clinical applications because they are limited by their high cost and rapid degradation ready. Our previous study found that nerve growth factor (NGF), a natural active protein extracted from cobra venom, has specific cartilage-inducing effects and is more effective than TGF-β1. To further study its molecular biology mechanism, RNA-Seq, bioinformatics analysis and experimental verification were performed. Based on the results, we predicted that snake venom NGF may up-regulate sox9 expression by inhibiting PHLPP1, subsequently activation of TNF signaling pathway, thereby inducing chondrogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). This project will study the role and mechanism of PHLPP1 and TNF signaling pathways in NGF-induced cartilage formation to elucidate the chondrogenic differentiation mechanism of snake venom NGF, which may provide a theoretical basis for the optimal design of cartilage-induced growth factors.