HO1 activates autophagy to protect intervertebral disc degeneration

Intervertebral disc degeneration (IDD) is majorly resulted from disordered extracellular matrix (ECM) metabolism, including decreased anabolism and increased catabolism activities in the nucleus pulposus (NP) cells of discs. Pro-inflammatory cytokines such as interleukin-1ß (IL-1ß) are considered to be potent mediators of ECM loss. We reported previously that hemeoxygenase-1 (HO-1) inducer cobalt protoporphyrin IX (CoPP) could attenuate the ECM breakdown which induced by IL-1ß, however, the underlying mechanism remains elusive. Here we found that autophagy family genes were involved in the HO-1 mediated anti-inflammatory processes in human NP cells by using high throughput RNA-Seq technique. These findings suggest that autophagy might play a role in inflammation related ECM metabolism disorder, thus offering a direction of our in-depth study and providing a framework for the searching of potential therapeutic targets in the treatment of IDD Overall design: Examination of the gene expression profile of human nucleus pulposus cells treated with CoPP or/and Interlukin-1ß

椎间盘退变（intervertebral disc degeneration, IDD）主要由细胞外基质（extracellular matrix, ECM）代谢紊乱引发，具体表现为椎间盘髓核（nucleus pulposus, NP）细胞的合成代谢活性降低、分解代谢活动增强。白细胞介素-1β（interleukin-1β, IL-1β）等促炎细胞因子被认为是ECM流失的强效介导因子。本团队既往研究证实，血红素加氧酶-1（hemeoxygenase-1, HO-1）诱导剂钴原卟啉IX（cobalt protoporphyrin IX, CoPP）可缓解IL-1β诱导的ECM降解，但具体分子机制仍不明确。本研究通过高通量RNA测序（high throughput RNA-Seq）技术，发现自噬相关基因参与了人NP细胞中HO-1介导的抗炎过程。上述结果提示，自噬可能在炎症相关的ECM代谢紊乱中发挥作用，可为后续深入研究提供方向，并为探寻治疗IDD的潜在治疗靶点构建理论框架。整体实验设计：检测经CoPP单独或联合白细胞介素-1β处理后人髓核细胞的基因表达谱。