Gruber Helen E, Ingram Jane A, Hoelscher Gretchen L, Marrero Emilio, Hanley Edward N
Department of Orthopaedic Surgery, Carolinas Medical Center, PO Box 32861, Charlotte, NC, USA.
Orthopaedic Research Biology, Carolinas Medical Center, Cannon Research Center, Room 304, PO Box 32861, Charlotte, NC, 28232, USA.
BMC Musculoskelet Disord. 2017 May 8;18(1):182. doi: 10.1186/s12891-017-1541-1.
Back pain and disc degeneration have a growing socioeconomic healthcare impact. Mucin 1 (MUC1) is a transmembrane glycoprotein whose extracellular and intracellular domains participate in cellular signaling. Little is currently known about the presence or role of MUC1 in human disc degeneration.
In this IRB-approved research study, 29 human disc specimens were analyzed for MUC1 immunohistochemical localization and gene expression, and annulus fibrosus (annulus) cells were also isolated and cultured in 3D. Microarray analysis assessed expression levels of MUC1 in healthy and degenerated disc tissue and in cells exposed to proinflammatory cytokines (IL-1ß or TNF-α).
MUC1 was shown to be present in annulus cells at the protein level using immunochemistry, and its expression was significantly upregulated in annulus tissue from more degenerated grade V discs compared to healthier grade I-II discs (p = 0.02). A significant positive correlation was present between the percentage of MUC1-positive cells and disc grade (p = 0.009). MUC1 expression in annulus cells cultured in 3D was also analyzed following exposure to IL-1ß or TNF-α; exposure produced significant MUC1 downregulation (p = 0.0006).
Here we present the first data for the constitutive presence of MUC1 in the human disc, and its altered expression during disc degeneration. MUC1 may have an important role in disc aging and degeneration by acting as a regulator in the hypoxic environment, helping disc cells to survive under hypoxic conditions by stabilization and by activation of HIF-1α as previously recognized in pancreatic cancer cells.
背痛和椎间盘退变对社会经济医疗保健的影响日益增大。黏蛋白1（MUC1）是一种跨膜糖蛋白，其细胞外和细胞内结构域参与细胞信号传导。目前对于MUC1在人类椎间盘退变中的存在情况或作用了解甚少。
在这项经机构审查委员会批准的研究中，对29个人类椎间盘标本进行了MUC1免疫组化定位和基因表达分析，同时还分离并在三维环境中培养了纤维环细胞。微阵列分析评估了MUC1在健康和退变椎间盘组织以及暴露于促炎细胞因子（IL-1β或TNF-α）的细胞中的表达水平。
采用免疫化学方法显示MUC1在纤维环细胞中呈蛋白水平存在，与健康的I-II级椎间盘相比，其在退变程度更高的V级椎间盘纤维环组织中的表达显著上调（p = 0.02）。MUC1阳性细胞百分比与椎间盘分级之间存在显著正相关（p = 0.009）。在暴露于IL-1β或TNF-α后，还分析了三维培养的纤维环细胞中MUC1的表达；暴露导致MUC1显著下调（p = 0.0006）。
在此我们首次提供了关于MUC1在人类椎间盘中的组成性存在及其在椎间盘退变过程中表达改变的数据。MUC1可能通过在缺氧环境中作为调节因子发挥重要作用，通过稳定作用以及如先前在胰腺癌细胞中所认识到的激活缺氧诱导因子-1α（HIF-1α）来帮助椎间盘细胞在缺氧条件下存活，从而在椎间盘老化和退变中发挥重要作用。
