Degradation of extracellular matrix (ECM) in intervertebral disks (IVDs) during IVD degeneration plays a vital role in low back pain (LBP). In healthy IVDs, synthesis and degradation of ECM are kept in balance by matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs. MMPs are enzymes responsible for ECM degradation, and their expression levels are known to increase in degenerated disks. However, the exact pathophysiological concentration of MMP-1 in the degenerated disks of patients with chronic LBP has not been reported previously. Factors secreted by human mesenchymal stem cells (hMSCs) have shown positive results in cell therapy of degenerated disks. The aim of this study was to investigate the pathophysiological MMP-1 concentration (in ng/mL) in degenerated disk tissue and to evaluate if conditioned media (CM) from hMSCs could mitigate the effects of MMP-1 at the detected levels in a 3D in vitro disk cell (DC) pellet model. Tissue levels of MMP-1 were quantified in disk tissue collected from 6 chronic LBP patients undergoing surgery. DC pellet cultures were performed to investigate the effects of MMP-1 alone and the effects of conditioned media (CM) in the presence of MMP-1. MMP-1 was introduced in the pellets on day 14 at concentrations of 5, 50, or 100 ng/mL. The pellets were harvested on day 28 and evaluated for cell viability, proliferation, and ECM production. The mean concentration of MMP-1 in disk tissue was 151 ng/mL. Results from pellet cultures demonstrated a higher number of viable cells, glycosaminoglycan production, and ECM accumulation in the CM group even in the presence of MMP-1 compared to the controls. However, the level decreased with increasing MMP-1 concentration. The results demonstrated that CM has the ability to mitigate matrix degradation property of MMP-1 up to 50 ng/mL suggesting that CM could potentially be used to treat early stages of disk degeneration.

中文翻译：

---

来自间充质干细胞的信号肽可以减轻退化椎间盘中 MMP-1 的人类水平

IVD 变性期间椎间盘 (IVD) 中细胞外基质 (ECM) 的降解在腰痛 (LBP) 中起着至关重要的作用。在健康的 IVD 中，ECM 的合成和降解通过基质金属蛋白酶 (MMP) 和 MMP 的组织抑制剂保持平衡。MMP 是负责 ECM 降解的酶，已知它们的表达水平会在退化的圆盘中增加。然而，之前尚未报道慢性 LBP 患者退化椎间盘中 MMP-1 的确切病理生理浓度。人类间充质干细胞 (hMSCs) 分泌的因子在退化椎间盘的细胞治疗中显示出积极的结果。本研究的目的是研究退化的椎间盘组织中的病理生理学 MMP-1 浓度（以 ng/mL 为单位），并评估来自 hMSCs 的条件培养基 (CM) 是否可以减轻 MMP-1 在 3D 中检测到的水平的影响。体外圆盘细胞 (DC) 颗粒模型。在从 6 名接受手术的慢性 LBP 患者收集的椎间盘组织中量化 MMP-1 的组织水平。进行 DC 颗粒培养以研究单独的 MMP-1 的影响和在 MMP-1 存在下条件培养基 (CM) 的影响。MMP-1 在第 14 天以 5、50 或 100 ng/mL 的浓度加入颗粒中。在第 28 天收获沉淀并评估细胞活力、增殖和 ECM 产生。椎间盘组织中 MMP-1 的平均浓度为 151 ng/mL。与对照组相比，即使在 MMP-1 存在的情况下，颗粒培养的结果表明，CM 组中的活细胞数量、糖胺聚糖产量和 ECM 积累量更高。然而，该水平随着 MMP-1 浓度的增加而降低。结果表明，CM 能够将 MMP-1 的基质降解特性降低至 50 ng/mL，这表明 CM 有可能用于治疗椎间盘退化的早期阶段。