Leptin and the intervertebral disc: a biochemical link exists between obesity, intervertebral disc degeneration and low back pain-an in vitro study in a bovine model
Leptin and the intervertebral disc: a biochemical link exists between obesity, intervertebral disc degeneration and low back pain-an in vitro study in a bovine model
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DOI：
10.1007/s00586-018-5778-7
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发表时间：
2019-02-01
影响因子：
2.8
通讯作者：
Urban, Jill
中科院分区：
文献类型：
--
作者：
Segar, Anand H.;Fairbank, Jeremy C. T.;Urban, Jill
目的 本研究的目的是确定瘦素对椎间盘 (IVD) 的影响，并确定这些反应是否在现有退变的环境中得到加强。肥胖是腰痛 (LBP) 和 IVD 退化的重要危险因素。脂肪因子，例如瘦素，是主要由脂肪组织产生的新型细胞因子，并且与降解和炎症过程有关。已知肥胖个体的血清瘦素浓度较高，IVD 细胞表达瘦素受体。我们假设脂肪因子，例如瘦素，介导肥胖、IVD变性和LBP之间的生化联系。方法使用牛椎间盘作为模型系统来研究瘦素介导的肥胖对椎间盘的生化影响。新鲜分离的细胞嵌入 3D 藻酸盐珠中，随后在不同浓度的瘦素（单独或与促炎细胞因子 TNF-α、IL-1β 或 IL-6 一起）下培养。分析了与一氧化氮、乳酸、糖胺聚糖的产生以及合成代谢和分解代谢基因表达相关的反应。结果瘦素影响细胞代谢，尤其导致蛋白酶和 NO 的产生更多。将瘦素添加到炎症环境中表现出明显的有害协同效应，NO、MMP 的产生量增加，促炎细胞因子的产生增强。结论瘦素可以启动参与 IVD 变性的过程。这种作用在存在退化和炎症的环境中会增强。因此，生化机制可能是肥胖、椎间盘退变和腰痛之间联系的基础。[图表]
Purpose The aim of this study was to identify the effects of leptin upon the intervertebral disc (IVD) and to determine whether these responses are potentiated within an environment of existing degeneration. Obesity is a significant risk factor for low back pain (LBP) and IVD degeneration. Adipokines, such as leptin, are novel cytokines produced primarily by adipose tissue and have been implicated in degradative and inflammatory processes. Obese individuals are known to have higher concentrations of serum leptin, and IVD cells express leptin receptors. We hypothesise that adipokines, such as leptin, mediate a biochemical link between obesity, IVD degeneration and LBP.Methods The bovine intervertebral disc was used as a model system to investigate the biochemical effects of obesity, mediated by leptin, upon the intervertebral disc. Freshly isolated cells, embedded in 3D alginate beads, were subsequently cultured under varying concentrations of leptin, alone or together with the pro-inflammatory cytokines TNF-alpha, IL-1 beta or IL-6. Responses in relation to production of nitric oxide, lactate, glycosaminoglycans and expression of anabolic and catabolic genes were analysed.Results Leptin influenced the cellular metabolism leading particularly to greater production of proteases and NO. Addition of leptin to an inflammatory environment demonstrated a marked deleterious synergistic effect with greater production of NO, MMPs and potentiation of pro-inflammatory cytokine production.Conclusions Leptin can initiate processes involved in IVD degeneration. This effect is potentiated in an environment of existing degeneration and inflammation. Hence, a biochemical mechanism may underlie the link between obesity, intervertebral disc degeneration and low back pain.[GRAPHICS]