Division of Cell Matrix Biology and Regenerative Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Stopford Building, Oxford Road, Manchester, M13 9PT, United Kingdom.
Department of Neurosurgery, Salford Royal NHS Foundation Trust, Manchester Academic Health Science Centre, Salford, United Kingdom.
Sci Rep. 2017 May 4;7(1):1501. doi: 10.1038/s41598-017-01567-w.
The nucleus pulposus (NP) of the intervertebral disc (IVD) demonstrates substantial changes in cell and matrix composition with both ageing and degeneration. While recent transcriptomic profiling studies have helped define human NP cell phenotype, it remains unclear how expression of these markers is influenced by ageing or degeneration. Furthermore, cells of the NP are thought to derive from the notochord, although adult NP lacks identifiable notochordal (NC) cells. This study aimed to confirm expression of previously identified NP and NC marker genes in adult human NP cells from a range of ages and degenerate states. Importantly, using gene expression analysis (N = 60) and immunohistochemistry (N = 56) the study demonstrates expression of NP markers FoxF1, Pax-1, keratin-8/18, carbonic anhydrase-12, and NC markers brachyury, galectin-3 and CD24 in cells of the NP irrespective of age or degeneration. Our immunohistochemical data, combined with flow cytometry (N = 5) which identified a small number of CA12Gal3TCD24 cells, suggests the possible presence of a sub-population of cells with an NC-like phenotype in adult NP tissue. These findings suggest that the NP contains a heterogeneous population of cells, which may possess varied phenotypic and functional profiles and thus warrant further investigation to improve our understanding of IVD homeostasis and repair.
椎间盘的髓核(NP)在细胞和基质组成上随着年龄增长和退变发生显著变化。虽然最近的转录组分析研究有助于定义人类 NP 细胞表型,但 NP 细胞中这些标志物的表达如何受年龄或退变影响仍不清楚。此外,NP 细胞被认为来源于脊索,但成年 NP 缺乏可识别的脊索细胞(NC)。本研究旨在确认一系列年龄和退变状态下成人 NP 细胞中先前鉴定的 NP 和 NC 标记基因的表达。重要的是,通过基因表达分析(N=60)和免疫组织化学(N=56),该研究证明了 NP 标记物 FoxF1、Pax-1、角蛋白-8/18、碳酸酐酶-12 和 NC 标记物 brachyury、半乳糖凝集素-3 和 CD24 在 NP 细胞中的表达,无论年龄或退变如何。我们的免疫组织化学数据,结合流式细胞术(N=5)鉴定出少量 CA12Gal3TCD24 细胞,提示成年 NP 组织中可能存在具有 NC 样表型的细胞亚群。这些发现表明 NP 包含一个异质细胞群体,这些细胞可能具有不同的表型和功能特征,因此需要进一步研究以提高我们对 IVD 稳态和修复的理解。