Francisco Vera, Pino Jesús, González-Gay Miguel Ángel, Lago Francisca, Karppinen Jaro, Tervonen Osmo, Mobasheri Ali, Gualillo Oreste
The NEIRID group (Neuroendocrine Interactions in Rheumatology and Inflammatory Diseases), SERGAS (Servizo Galego de Saude) and IDIS (Instituto de Investigación Sanitaria de Santiago), C027-Research Laboratory 9, Santiago University Clinical Hospital, Santiago de Compostela, Spain.
Epidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, Universidad de Cantabria and IDIVAL, Hospital Universitario Marqués de Valdecilla, Santander, Spain.
Nat Rev Rheumatol. 2022 Jan;18(1):47-60. doi: 10.1038/s41584-021-00713-z. Epub 2021 Nov 29.
Intervertebral disc (IVD) degeneration is a common finding on spine imaging that increases in prevalence with age. IVD degeneration is a frequent cause of low back pain, which is a leading cause of disability. The process of IVD degeneration consists of gradual structural change accompanied by severe alterations in metabolic homeostasis. IVD degeneration, like osteoarthritis, is a common comorbidity in patients with obesity and type 2 diabetes mellitus, two metabolic syndrome pathological conditions in which adipokines are important promoters of low-grade inflammation, extracellular matrix degradation and fibrosis. Impairment in white adipose tissue function, due to the abnormal fat accumulation in obesity, is characterized by increased production of specific pro-inflammatory proteins such as adipokines by white adipose tissue and of cytokines such as TNF by immune cells of the stromal compartment. Investigations into the immunometabolic alterations in obesity and type 2 diabetes mellitus and their interconnections with IVD degeneration provide insights into how adipokines might affect the pathogenesis of IVD degeneration and impair IVD function and repair. Toll-like receptor-mediated signalling has also been implicated as a promoter of the inflammatory response in the metabolic alterations associated with IVD and is thus thought to have a role in IVD degeneration. Pathological starvation, obesity and adipokine dysregulation can result in immunometabolic alterations, which could be targeted for the development of new therapeutics.
椎间盘（IVD）退变是脊柱影像学上的常见表现，其患病率随年龄增长而增加。IVD退变是下腰痛的常见原因，而下腰痛是导致残疾的主要原因。IVD退变过程包括结构逐渐改变，并伴有代谢稳态的严重改变。与骨关节炎一样，IVD退变是肥胖和2型糖尿病患者的常见合并症，肥胖和2型糖尿病是两种代谢综合征病理状态，其中脂肪因子是低度炎症、细胞外基质降解和纤维化的重要促进因子。肥胖时异常脂肪堆积导致白色脂肪组织功能受损，其特征是白色脂肪组织产生特定促炎蛋白如脂肪因子增加，以及基质区免疫细胞产生细胞因子如肿瘤坏死因子增加。对肥胖和2型糖尿病中免疫代谢改变及其与IVD退变的相互关系的研究，为脂肪因子如何影响IVD退变的发病机制以及损害IVD功能和修复提供了见解。Toll样受体介导的信号传导也被认为是与IVD相关的代谢改变中炎症反应的促进因子，因此被认为在IVD退变中起作用。病理性饥饿、肥胖和脂肪因子失调可导致免疫代谢改变，这可能成为开发新疗法的靶点。
