Raines Benjamin T, Stannard James T, Stricklin Olivia E, Stoker Aaron M, Choma Theodore J, Cook James L
14716University of Missouri, Columbia, MO, USA.
University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
Global Spine J. 2022 Jan;12(1):61-69. doi: 10.1177/2192568220948031. Epub 2020 Sep 16.
Controlled laboratory study.
To investigate the impact of exposure to physiologically relevant caffeine concentrations on intervertebral disc (IVD) cell viability and extracellular matrix composition (ECM) in a whole organ culture model as potential contributing mechanisms in development and progression of IVD disorders in humans. Primary outcome measures were IVD viable cell density (VCD) and ECM composition.
A total of 190 IVD whole organ explants from tails of 16 skeletally mature rats-consisting of cranial body half, endplate, IVD, endplate, and caudal body half-were harvested. IVD explants were randomly assigned to 1 of 2 groups: uninjured (n = 90) or injured (20G needle disc puncture/aspiration method, n = 100). Explants from each group were randomly assigned to 1 of 3 treatment groups: low caffeine (LCAF: 5 mg/L), moderate caffeine (MCAF: 10 mg/L), and high caffeine (HCAF: 15 mg/L) concentrations.
Cell viability was significantly higher in the low-caffeine group compared with the high-caffeine group at day 7 ( = .037) and in the low-caffeine group compared with the medium- and high-caffeine groups at day 21 ( ≤ .004). Analysis of ECM showed that all uninjured and control groups had significantly higher ( < .05) glycosaminoglycan concentrations compared with all injured groups. Furthermore, we observed a temporal, downward trend in proteoglycan to collagen ratio for the caffeine groups.
Caffeine intake may be a risk factor for IVD degeneration, especially in conjunction with disc injury. Mechanisms for caffeine associated disc degeneration may involve cell and ECM, and further studies should elucidate mechanistic pathways and potential benefits for caffeine restriction.
对照实验室研究。
在全器官培养模型中,研究暴露于生理相关咖啡因浓度对椎间盘(IVD)细胞活力和细胞外基质组成(ECM)的影响,作为人类IVD疾病发生和发展的潜在促成机制。主要结局指标为IVD活细胞密度(VCD)和ECM组成。
从16只骨骼成熟大鼠的尾巴上共采集190个IVD全器官外植体,包括颅体半部分、终板、IVD、终板和尾体半部分。IVD外植体随机分为2组中的1组:未损伤组(n = 90)或损伤组(20G针椎间盘穿刺/抽吸法,n = 100)。每组的外植体随机分为3个处理组中的1组:低咖啡因(LCAF:5 mg/L)、中度咖啡因(MCAF:10 mg/L)和高咖啡因(HCAF:15 mg/L)浓度组。
在第7天,低咖啡因组的细胞活力显著高于高咖啡因组(P = .037);在第21天,低咖啡因组的细胞活力显著高于中、高咖啡因组(P≤.004)。ECM分析表明,与所有损伤组相比,所有未损伤组和对照组的糖胺聚糖浓度显著更高(P < .05)。此外,我们观察到咖啡因组蛋白聚糖与胶原蛋白的比例呈时间性下降趋势。
摄入咖啡因可能是IVD退变的一个危险因素,尤其是与椎间盘损伤相关时。咖啡因相关椎间盘退变的机制可能涉及细胞和ECM,进一步的研究应阐明其机制途径以及限制咖啡因摄入的潜在益处。