Holguin Nilsson, Aguilar Rhiannon, Harland Robin A, Bomar Bradley A, Silva Matthew J
Department of Orthopedics, Washington University, St. Louis, Missouri; and
Department of Orthopedics, Washington University, St. Louis, Missouri; and.
J Appl Physiol (1985). 2014 Jun 15;116(12):1551-60. doi: 10.1152/japplphysiol.01322.2013. Epub 2014 May 1.
Murine lumbar and coccygeal (tail) regions of spines are commonly used to study cellular signaling of age-related disc diseases, but the tissue-level changes of aging intervertebral discs and vertebrae of each spinal region remain unclear. Furthermore, the impact of aging lumbar and coccygeal discs on Wnt/β-catenin signaling, which is putatively involved in the catabolism of intervertebral discs, is also unclear. We compared disc/vertebrae morphology and mechanics and biochemical composition of intervertebral discs from lumbar and coccygeal regions between young (4-5 mo) and old (20-22 mo) female C57BL/6 mice. Center intervertebral disc height from both regions was greater in old discs than young discs. Compared with young, old lumbar discs had a lower early viscous coefficient (a measure of stiffness) by 40%, while conversely old coccygeal discs were stiffer by 53%. Biochemically, old mice had double the collagen content in lumbar and coccygeal discs of young discs, greater glycosaminoglycan in lumbar discs by 37%, but less glycosaminoglycan in coccygeal discs by 32%. Next, we compared Wnt activity of lumbar and coccygeal discs of 4- to 5-mo and 12- to 14-mo TOPGAL mice. Despite the disc-specific changes, aging decreased Wnt signaling in the nucleus pulposus from both spinal regions by ≥64%. Compared with young, trabecular bone volume/tissue volume and ultimate force were less in old lumbar vertebrae, but greater in old coccygeal vertebrae. Thus intervertebral discs and vertebrae age in a spinal region-dependent manner, but these differential age-related changes may be uncoupled from Wnt signaling. Overall, lumbar and coccygeal regions are not interchangeable in modeling human aging.
小鼠腰椎和尾椎区域的脊柱常用于研究与年龄相关的椎间盘疾病的细胞信号传导,但每个脊柱区域的老化椎间盘和椎体的组织水平变化仍不清楚。此外,老化的腰椎和尾椎椎间盘对Wnt/β-连环蛋白信号传导的影响也不清楚,该信号传导被认为与椎间盘的分解代谢有关。我们比较了年轻(4-5个月)和年老(20-22个月)雌性C57BL/6小鼠腰椎和尾椎区域椎间盘/椎体的形态、力学和生化组成。两个区域的中央椎间盘高度在老年椎间盘比年轻椎间盘更大。与年轻相比,老年腰椎间盘的早期粘性系数(一种刚度测量)低40%,而相反,老年尾椎椎间盘更硬,增加了53%。生化方面,老年小鼠腰椎和尾椎椎间盘的胶原蛋白含量是年轻椎间盘的两倍,腰椎间盘的糖胺聚糖增加37%,但尾椎椎间盘的糖胺聚糖减少32%。接下来,我们比较了4至5个月和12至14个月大的TOPGAL小鼠腰椎和尾椎椎间盘的Wnt活性。尽管存在椎间盘特异性变化,但老化使两个脊柱区域髓核中的Wnt信号传导降低≥64%。与年轻相比,老年腰椎椎体的小梁骨体积/组织体积和极限力较小,但老年尾椎椎体则较大。因此,椎间盘和椎体以脊柱区域依赖的方式老化,但这些与年龄相关的差异变化可能与Wnt信号传导解耦。总体而言,在模拟人类衰老方面,腰椎和尾椎区域不可互换。