Snuggs Joseph W, Day Rebecca E, Bach Frances C, Conner Matthew T, Bunning Rowena A D, Tryfonidou Marianna A, Le Maitre Christine L
Biomolecular Sciences Research Centre Sheffield Hallam University Sheffield UK.
Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine Utrecht University Utrecht The Netherlands.
JOR Spine. 2019 Mar 22;2(1):e1049. doi: 10.1002/jsp2.1049. eCollection 2019 Mar.
The intervertebral disc (IVD) is a highly hydrated tissue, the rich proteoglycan matrix imbibes water, enabling the disc to withstand compressive loads. During aging and degeneration increased matrix degradation leads to dehydration and loss of function. Aquaporins (AQP) are a family of transmembrane channel proteins that selectively allow the passage of water in and out of cells and are responsible for maintaining water homeostasis in many tissues. Here, the expression of all 13 AQPs at gene and protein level was investigated in human and canine nondegenerate and degenerate IVDs to develop an understanding of the role of AQPs during degeneration. Furthermore, in order to explore the transition of notochordal cells (NCs) towards nucleus pulposus (NP) cells, AQP expression was investigated in canine IVDs enriched in NCs to understand the role of AQPs in IVD maturation. AQP0, 1, 2, 3, 4, 5, 6, 7, and 9 were expressed at gene and protein level in both nondegenerate and degenerate human NP tissue. AQP2 and 7 immunopositivity increased with degeneration in human NP tissue, whereas AQP4 expression decreased with degeneration in a similar way to AQP1 and 5 shown previously. All AQP proteins that were identified in human NP tissue were also expressed in canine NP tissue. AQP2, 5, 6, and 9 were found to localize to vacuole-like membranes and cell membranes in NC cells. In conclusion, AQPs were abundantly expressed in human and canine IVDs. The expression of many AQP isotypes potentially alludes to multifaceted functions related to adaption of NP cells to the conditions they encounter within their microenvironment in health and degeneration. The presence of AQPs within the IVD may suggest an adaptive role for these water channels during the development and maintenance of the healthy, mature IVD.
椎间盘(IVD)是一种高度水合的组织,其丰富的蛋白聚糖基质吸收水分,使椎间盘能够承受压缩负荷。在衰老和退变过程中,基质降解增加导致脱水和功能丧失。水通道蛋白(AQP)是一类跨膜通道蛋白家族,可选择性地允许水进出细胞,并负责维持许多组织中的水平衡。在此,研究了13种AQP在人及犬类非退变和退变IVD中的基因和蛋白水平表达,以了解AQP在退变过程中的作用。此外,为了探索脊索细胞(NCs)向髓核(NP)细胞的转变,研究了富含NCs的犬类IVD中的AQP表达,以了解AQP在IVD成熟中的作用。AQP0、1、2、3、4、5、6、7和9在非退变和退变的人NP组织中均在基因和蛋白水平表达。在人NP组织中,AQP2和7的免疫阳性随着退变而增加,而AQP4的表达随着退变而降低,与之前显示的AQP1和5的方式相似。在人NP组织中鉴定出的所有AQP蛋白也在犬类NP组织中表达。发现AQP2、5、6和9定位于NC细胞中的液泡样膜和细胞膜。总之,AQP在人及犬类IVD中大量表达。许多AQP同种型的表达可能暗示了与NP细胞适应其在健康和退变微环境中所遇到条件相关的多方面功能。IVD中AQP的存在可能表明这些水通道在健康、成熟IVD的发育和维持过程中具有适应性作用。