Exercise accelerated the degeneration of lumbar IVDs from surgical lumbar instability, similar to the clinical degeneration process

Given the leading cause of disability worldwide, low back pain (LBP) is recognized as a pivotal socio-economic challenge to the aging population, which is importantly attributed to intervertebral disc degeneration (IVDD), a highly prevalent affliction of aging. Elastic nucleus pulposus (NP) tissue is essential for maintenance of IVD structural and functional integrity. Native NP cells exhibit crucial functions for regulating extracellular matrix homeostasis, constructing an accommodating biomechanical environment and maintaining the gelatinous property of NP tissue. Mechanical stresses, including compulsion position and aberrant mechanical loading, are regarded as etiological factors of IVDD, and to further investigate the effect of mechanical exercise during the degeneration of IVDs, we surgically resected the lumbar 4th-lumbar 5th (L4-L5) spinous processes of the rat spine along with the supraspinous and interspinous ligaments to induce lumbar surgical instability (LSI). Additionally, we applied RNA sequencing technology to describe the degeneration-associated molecular atlas of the LSI model during exercise, and found that exercise accelerated the degenerative process of IVDs from LSI, which is involved in cytosolic DNA sensing-mediated inflammatory activation, similar to the degenerative patterns of the clinical IVDD process.作为全球范围内导致残疾的首要原因，下背痛（low back pain, LBP）被视为人口老龄化进程中的关键社会经济挑战，其重要诱因之一为椎间盘退变（intervertebral disc degeneration, IVDD）——一种高发的老年性疾患。弹性髓核（elastic nucleus pulposus, NP）组织对维持椎间盘结构与功能完整性至关重要。天然NP细胞在调控细胞外基质稳态、构建适宜的生物力学环境以及维持NP组织胶状特性方面发挥关键作用。包括压迫体位与异常机械负荷在内的机械应力被认为是IVDD的致病因素。为进一步探究机械运动在椎间盘退变过程中的作用，本研究通过手术切除大鼠脊柱第4腰椎-第5腰椎（lumbar 4th-lumbar 5th, L4-L5）棘突及棘上、棘间韧带，构建腰椎手术不稳模型（lumbar surgical instability, LSI）。此外，本研究采用RNA测序（RNA sequencing）技术描绘了运动状态下LSI模型的退变相关分子图谱，发现运动可加速LSI模型椎间盘的退变进程，该过程涉及胞质DNA感知介导的炎症激活，与临床IVDD的退变模式相似。