Orthopaedic Biomechanics, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.
Institute for Biomechanics, Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland.
J Orthop Res. 2019 May;37(5):1110-1116. doi: 10.1002/jor.24268. Epub 2019 Apr 1.
Inflammatory cytokines play an important role in intervertebral disc degeneration. Although largely produced by immune cells, nucleus pulposus (NP) cells can also secrete them under various conditions, for example, under free swelling. Thus, tissue hypotonicity may be an inflammatory trigger for NP cells. The aim of this study was to investigate whether decreased tonicity under restricted swelling conditions (as occurring in early disc degeneration) could initiate an inflammatory cascade that mediates further degeneration. Healthy bovine NP tissue was balanced against different PEG concentrations (0-30%) to obtain various tissue tonicities. Samples were then placed in an artificial annulus (fixed volume) and were cultured for 3, 7, or 21 days, with free swelling NP as control. Tissue content (water, glycosaminoglycan, collagen) was analyzed, and both the tissue and medium were screened for tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), prostaglandin-E (PGE ), and nitric oxide (NO). A range of tonicities (isotonic to hypotonic) was present at day 3 in the PEG-treated samples. However, during culture, the tonicity range narrowed as GAGs leached from the tissue. TNF-α and IL-1β were below detection limits in all conditions, while mid- and downstream inflammatory cytokines were detected. This may suggest that the extracellular environment directly affects NP cells instead of inducing a classical inflammatory cascade. Furthermore, IL-8 increased in swelling restricted samples, while IL-6 and PGE were elevated in free swelling controls. These findings may suggest the involvement of different mechanisms in disc degeneration with intact AF compared to herniation, and encourage further investigation. © 2019 The Authors. Journal of Orthopaedic Research® Published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society. J Orthop Res.
炎性细胞因子在椎间盘退变中起着重要作用。尽管主要由免疫细胞产生，但核髓（NP）细胞在各种条件下也可以分泌它们，例如在自由肿胀下。因此，组织低渗可能是 NP 细胞的炎症触发因素。本研究的目的是研究在限制肿胀条件下（如早期椎间盘退变中发生的情况），组织低渗是否可以引发炎症级联反应，从而介导进一步的退变。将健康的牛 NP 组织与不同浓度的 PEG（0-30%）平衡，以获得不同的组织渗透压。然后将样品置于人工环（固定体积）中，并在自由肿胀 NP 作为对照的情况下培养 3、7 或 21 天。分析组织含量（水、糖胺聚糖、胶原蛋白），并筛选组织和培养基中的肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）、白细胞介素-8（IL-8）、前列腺素-E（PGE）和一氧化氮（NO）。在 PEG 处理的样品中，第 3 天存在一系列渗透压（等渗至低渗）。然而，在培养过程中，由于 GAG 从组织中渗出，渗透压范围变窄。在所有条件下，TNF-α 和 IL-1β 均低于检测限，而中效和下游炎性细胞因子则被检测到。这可能表明细胞外环境直接影响 NP 细胞，而不是诱导经典的炎症级联反应。此外，在肿胀受限的样本中，IL-8 增加，而在自由肿胀对照中，IL-6 和 PGE 升高。这些发现可能表明，与完整的 AF 相比，椎间盘退变中涉及不同的机制，这鼓励进一步的研究。©2019 作者。骨科研究杂志®由 Wiley 期刊出版公司代表骨科研究协会出版。J 骨科 Res。
