体外软骨再生为软骨缺损修复提供了新策略，但力学强度不足严重阻碍了其临床转化。课题组前期证实静水压能显著提高体外再生软骨力学强度，但其作用机制不清。基因芯片分析发现，静水压组c-Jun氨基末端激酶（JNK2/MAPK9）表达水平显著上调。查阅文献证实JNK2的确与软骨再生密切相关。据此提示：JNK2在静水压促进体外软骨再生过程中发挥了重要作用，但JNK2如何介导了这一过程尚不清楚。要阐明其详细分子机制，需回答以下关键科学问题：JNK2是否是静水压调控体外软骨再生的关键通路？静水压如何上调了JNK2表达？JNK2又通过哪些下游通路促进了体外软骨再生？围绕上述问题，本项目拟通过JNK2上、下游相关信号通路的抑制/激活及相关因子的阻断，结合软骨再生效果评估，从基因、蛋白、细胞、组织多水平阐明JNK2介导静水压调控体外软骨再生的分子机制，为推动体外软骨再生技术临床应用转化奠定技术基础和理论依据。

Cartilage regenerationin vitro provide a new strategy for clinical repairment of cartilage defect, however, the translation from tissue engineering cartilage to clinical application has still not been accomplished because of the poor quality of in vitro Tissue engineering cartilage. In our previous study, hydrostatic pressure stimulation model has been set up and improved the mechanical strength of regeneration in vitro cartilage，but the mechanism is still unclear. Furthermore, The results of gene arrays indicated that c-jun N-terminal kinases(JNK2/MAPK9) gene expression was significantly increased in hydrostatic pressure group. A large number of studies also have shown that JNK2 is closely related with cartilage regeneration. Above scientific phenomenon reminder that JNK2 plays an important role in cartilage regeneration in vitro under hydrostatic pressure. However, it is unclear how JNK2 mediates this process，so several important issues still need to be elucidated. For example: Is JNK2 is the key pathway of cartilage regeneration in vitro under hydrostatic pressure ? What is the molecular mechanism of increased expression of JNK2 through hydrostatic pressure? Which factor plays an important role in JNK2 promoting cartilage regeneration in vitro by downstream? Around these issues, our research intends to inhibit or activate the related downstream and upstream signaling pathways of JNK2 to clarify molecular mechanism of cartilage regeneration in vitro mediated by JNK2 under hydrostatic pressure, which combined with cartilage regeneration effect evaluation from the level of gene, protein, cell, tissue. It is expected that the mechanical strength of in vitro engineered cartilage can be significantly enhanced by solving these problem, which apparently helps to establish the technology and theoretical basis for the clinical translation of in vitro engineered cartilage.