Basic research on mechanism of lumbar disc degeneration and ne w development of treatment

Era/GRIP1和转化生长因子-b/MKK6/p38MAPK通路之间的交叉通路通过调节细胞外基质的表达对软骨代谢起保护作用；PHD3通过调节核因子-αB信号调控肿瘤坏死因子-κ的活性。当PHD3被抑制时，肿瘤坏死因子-α诱导的分解代谢标志物包括ADAMTS5、Syndecan4、MMP13的表达显著减少，同时凝集素和II型胶原的表达也得到恢复。在活体研究中，退行性腰椎侧弯患者的Cobb角与CPII呈显著正相关。结果提示退行性腰椎侧弯患者II型胶原合成和降解水平较高。这些发现可能会导致开发一种治疗软骨退变的新方法。

Crosstalks between ERa/GRIP1 and TGF -b/MKK6/p38 MAPK pathway have protective roles on cartilage metabolism via regulating the extracellular matrices expression.PHD3 controls TNF-α activity by modulating NF-κB signaling. When PHD3 is silenced, there is a significant decrease in TNF -α-induced expression of catabolic markers that include ADAMTS5, syndecan4, MMP13, and at the same time, there is restoration of aggrecan and collagen type II expression. In vivo study, there was a significant positive correlation between the Cobb angle and CPII in degenerative lumbar scoliosis. The results suggest degenerative lumbar scoliosis patients have higher levels of type II collagen synthesis and degradation. These findings may lead to the development of a novel therapeutic approach for cartilage degeneration