Department of Physiology and Pharmacology, Schulich School of Medicine & Dentistry, The Bone and Joint Institute, The University of Western Ontario, London, Canada.
Sydney Medical School, University of Sydney, Sydney, Australia.
Connect Tissue Res. 2020 Jan;61(1):63-81. doi: 10.1080/03008207.2019.1665034. Epub 2019 Oct 10.
: The intervertebral disc (IVD) is composed of cell types whose subtle phenotypic differences allow for the formation of distinct tissues. The role of the nucleus pulposus (NP) in the initiation and progression of IVD degeneration is well established; however, the genes and pathways associated with NP degeneration are poorly characterized.: Using a genetic strategy for IVD lineage-specific fluorescent reporter expression to isolate cells, gene expression and bioinformatic analysis was conducted on the murine NP at 2.5, 6, and 21 months-of-age and the annulus fibrosus (AF) at 2.5 and 6 months-of-age. A subset of differentially regulated genes was validated by qRT-PCR.: Transcriptome analysis identified distinct profiles of NP and AF gene expression that were remarkably consistent at 2.5 and 6 months-of-age. and were increased >50-fold in the AF relative to NP. The most highly enriched NP genes included and , members of the cadherin superfamily, and microRNAs and . Changes in the NP between 2.5 and 6 months-of-age were associated with up-regulation of molecular functions linked to laminin and Bmp receptor binding (including up-regulation of & ), with the most up-regulated genes being , and . NP degeneration was associated with molecular functions linked to alpha-actinin binding (including up-regulation of & ) and cytoskeletal protein binding, with the overall most up-regulated genes being and .: This study provided insight into the phenotypes of NP and AF cells, and identified candidate pathways that may regulate degeneration.
椎间盘（IVD）由细胞类型组成，其微妙的表型差异允许形成不同的组织。核髓（NP）在 IVD 退变的发生和进展中的作用已得到充分证实；然而，与 NP 退变相关的基因和途径尚未得到充分描述。
使用用于 IVD 谱系特异性荧光报告基因表达的遗传策略来分离细胞，对 2.5、6 和 21 月龄的小鼠 NP 以及 2.5 和 6 月龄的纤维环（AF）进行了基因表达和生物信息学分析。通过 qRT-PCR 验证了一组差异调节基因。
转录组分析确定了 NP 和 AF 基因表达的不同谱，在 2.5 和 6 月龄时非常一致。在 AF 中，与 NP 相比， 和 的表达增加了 50 多倍。最丰富的 NP 基因包括钙粘蛋白超家族成员 和 ，以及 microRNAs 和 。NP 从 2.5 到 6 月龄之间的变化与与层粘连蛋白和 Bmp 受体结合相关的分子功能的上调有关（包括 和 的上调），上调最明显的基因是 、 和 。NP 退变与与α-辅肌动蛋白结合相关的分子功能（包括 和 的上调）和细胞骨架蛋白结合有关，上调最明显的基因是 和 。
本研究深入了解了 NP 和 AF 细胞的表型，并确定了可能调节退变的候选途径。
