TonEBP-deficiency accelerates age-dependent intervertebral disc degeneration underscored by matrix remodeling, cytoskeletal rearrangements, and changes in proinflammatory gene expression

Our studies show that TonEBP-deficiency causes pronounced degeneration of all three intervertebral disc compartments with greater incidence of herniation in the mouse. The disc phenotype is marked by extracellular matrix remodeling, actin cytoskeleton rearrangements, and suppressed proinflammatory gene expression, advancing our understanding of the contributions of TonEBP in intervertebral disc homeostasis and disease. We used microarray to explore the transcriptomics of differentially expressed genes of annulus fibrosus (AF) and nucleus pulposus (NP) tissue in TonEBP haploinsufficient mice on a C57BL/6 background. AF and NP tissue were dissected from lumbar discs (L1-S1) of 12-month-old TonEBP haploinsufficient and wild-type mice (n=3). RNA extraction and hybridization on Affymetrix microarrays.

本研究证实，张力反应元件结合蛋白（TonEBP）缺陷可导致小鼠椎间盘三个分区均出现显著退变，且椎间盘突出的发生率更高。该椎间盘表型以细胞外基质重塑、肌动蛋白细胞骨架重排及促炎基因表达受抑为特征，加深了我们对TonEBP在椎间盘稳态与疾病进程中作用的认知。我们采用基因芯片技术，对C57BL/6背景下TonEBP单倍剂量不足小鼠的纤维环（annulus fibrosus, AF）与髓核（nucleus pulposus, NP）组织的差异表达基因转录组展开探究。从12月龄TonEBP单倍剂量不足小鼠与野生型小鼠的腰椎间盘（L1-S1节段）中分离获取AF与NP组织（每组n=3）。随后完成RNA提取，并在Affymetrix基因芯片上完成杂交实验。