炎症因子在椎间盘退变中作用的研究进展

椎间盘退变（intervertebral disc degeneration,IDD）是一个慢性演变过程,也是引起腰背痛的常见原因之一,但目前对于引起IDD的具体原因尚不明确。以往的研究表明,IDD是一个多因素相互作用的复杂过程,其主要特征是椎间盘细胞凋亡、细胞外基质破坏、细胞表型改变。此外,新的证据表明白细胞介素和肿瘤坏死因子等炎症因子在退变椎间盘（intervertebral disc,IVD）中高度表达。同时,已有研究表明,诸多炎症因子可能在IDD发生发展中有着重要的作用,随着退变的进行,IVD内炎症因子水平升高,聚集蛋白聚糖（aggrecan,AGC）和胶原（collagen,COL）降解增加,IVD细胞表型改变,这为其作为潜在治疗靶点的临床应用提供了理论依据。因此本文旨在归纳近些年炎症因子的研究热点,论述其在IDD过程中的具体作用,为IDD的治疗提供新的思路。     

椎间盘源性腰痛的发病机制与治疗进展

椎间盘退变（intervertebral disc degeneration, IDD）是腰痛（low back pain, LBP）的主要原因之一，由IDD引起的LBP被称为椎间盘源性LBP。导致IDD因素众多，本文重点探讨炎症因子调控、神经血管增生在椎间盘源性LBP形成过程中的作用，并回顾细胞、生长因子、基因等生物疗法在治疗IDD及椎间盘源性LBP的进展。     

椎间盘退变遗传学机制的研究进展

椎间盘退变性疾病（degenerative disc disease,DDD）是指由椎间盘退变（intervertebral disc degeneration,IDD）引起的以颈肩腰腿疼痛为主要表现的临床症候群,包括了临床上常见的颈、腰椎间盘突出症,颈椎病,退变引起的椎间盘源性腰痛,退变性颈、腰椎不稳症和退变性颈、腰椎管狭窄症等.人的一生中均会出现或轻或重的DDD症状.据资料统计,DDD患者占美国骨科住院人数的1/3以上.了解IDD的发生机制必将为预测和治疗DDD提供最佳途径.     

微小RNA在椎间盘退变中的作用机制及治疗研究进展

椎间盘（intervertebral disc,IVD）是由髓核（nucleus pulposus,NP）、纤维环（annular fibrosus,AF）及终板软骨（cartilaginous endplates,CEP）构成。在生理情况下,IVD是人体最大的无血管器官,营养物质只能通过CEP的扩散来获取。年龄的增加及机械应力改变等因素会导致IVD退变脱水,并可能伴随着椎间盘血管化及神经植入等现象的发生。腰椎间盘退变（intervertebral disc degeneration,IDD）是引起腰痛的主要原因。目前IDD的发病机制尚不明确,遗传、年龄、环境、吸烟、肥胖、糖尿病、高血压、重体力劳动等均是IDD的发病因素。多项研究证实细胞增殖、凋亡、炎症反应、氧化应激、自噬等在IDD中发挥着重要作用。微小RNA（MicroRNA,miRNA）是一类非编码小分子RNA,在真核生物中大量存在,长度约18~22个核酸。miRNA在人体几乎所有生理及病理活动中均发挥重要作用。近年来,大量研究发现miRNA与IDD密切相关。目前已知的与IDD相关的miRNA种类繁多,miRNA与IDD的关系错综复杂,且仍未完全明确。笔者将不同的miRNA根据功能种类进行综合描述,初步明确miRNA与IDD的关系,为IDD的临床诊断治疗提供新的思路。     

褪黑素在椎间盘退变中的研究进展

椎间盘退变是下腰痛的主要因素之一,随着老年社会的到来,其发病率逐年升高,由于椎间盘退变(intervertebral disc degeneration,IDD)致病因素众多,其发病机制尚不清楚,目前仍无有效治疗药物。褪黑素(melatonin,MT)作为松果体分泌的一种神经内分泌激素,因其卓越的抗氧化应激、抗炎及抗细胞凋亡等作用在肿瘤、年龄相关性退行性疾病等邻域有着广泛的研究,本文就MT延缓IDD机制研究做一综述,为后续相关研究提供参考。     

细胞移植治疗椎间盘退变的研究进展

椎间盘退变(intervertebral disc degeneration,IDD)是诸多脊柱肌肉与骨骼系统机能紊乱的潜在病因,也是腰痛产生的源头。在临床上可表现为椎间盘突出、椎管狭窄及脊柱不稳等。对于椎间盘退变性疾病,目前的治疗方法分     

椎问盘退变遗传学机制的研究进展

椎间盘退变性疾病(degenerative disc disease,DDD)是指由椎间盘退变(intervertebral disc degeneration,IDD)引起的以颈肩腰腿疼痛为主要表现的临床症候群,包括了临床上常见的颈、腰椎间盘突出症,颈椎病,退变引起的椎间盘源性腰痛,退变性颈、腰椎不稳症和退变性颈、腰椎管狭窄症等.人的一生中均会出现或轻或重的DDD症状.据资料统计,DDD患者占美国骨科住院人数的1/3以上.了解IDD的发生机制必将为预测和治疗DDD提供最佳途径.     

椎间盘退变的遗传学机制研究进展

椎间盘退变（intervertebral disc degeneration，IDD）是一系列脊柱退行性疾病的发生前提和基础病理过程，临床上常表现为椎管狭窄、脊柱节段不稳、腰腿痛、颈椎病、椎间盘突出等病症。传统的观点认为IDD主要与过度的身体负荷引起的损伤以及衰老过程中伴随出现的变化有关。随着相关研究的不断深入，人们对IDD及其病因的认识有了巨大的进步。近年来的一些研究，特别是对同卵双生者IDD的研究发现遗传因素可能在IDD的发生发展中起重要作用。本文就相关研究情况作一综述。     

维生素D受体基因多态性和椎间盘退变的相关性研究进展

文献报道生理性退变、重体力劳动、椎间盘外伤、过度劳累、吸烟等均为椎间盘退变(intervertebral disc degeneration,IDD)的相关因素。而近年来随着研究逐渐深入     

髓核细胞退变相关信号通路的研究进展

正椎间盘退行性疾病(disc degeneration disease,DDD)是临床常见病和多发病,而DDD的前提和基本病理过程~([1])被认为与椎间盘退变(intervertebral disc degeneration,IVDD)密切相关,因此,延缓乃至逆转IVDD进程是治疗DDD的必由之路。信号通路,自从1972年被提出后备受广大研究者青睐,近年来在IVDD研究领域也逐渐受到重视~([2]),尤其在髓核细胞退变方面,取得了大量的研究成果。     

Novel stepwise model of intervertebral disc degeneration with intact annulus fibrosus to test regeneration strategies

Novel preclinical models that do not damage the annulus fibrosus (AF) of the intervertebral disc are required to study the efficacy of new regenerative strategies for the nucleus pulposus (NP). The aim of the study was to characterize a preclinical ovine model of intervertebral disc degeneration (IDD) induced by endplate (EP) damage and repair via the transpedicular approach, with or without partial nucleotomy, while keeping the AF intact. Twelve adult sheep were used. By the transpedicular approach, a 2 mm tunnel was drilled to the NP through the EP. A partial‐nucleotomy was performed. The tunnel was sealed using a polyurethane scaffold. Lumbar discs were assigned to different groups: L1‐2: nucleotomy; L2‐3: EP tunnel; L3‐4: nucleotomy + EP repair; L4‐5: EP tunnel + repair; L5‐6: control. X‐Ray and MRI were performed at 0, 1, 3, and 6 months after surgery. Disc height and MRI indexes were calculated. Macro‐ and micro‐morphology were analyzed. Pfirrmann and Thompson grades were assigned. The treated discs exhibited a progressive decrease in NP signal intensity and MRI index, displaying specific grades of degeneration based on the surgical treatment. According to Pfirrmann and Thompson grades different procedures were staged as: EP tunnel + repair: grade‐II; EP tunnel: grade‐III, nucleotomy + EP repair: grade‐IV; nucleotomy: grade‐V. A new stepwise model of IDD to study and test safety and efficacy of novel strategies for NP regeneration has been characterized. The different degrees of IDD have been observed similar to Pfirrmann and Thompson grading system. The intact AF allows for loading studies and eliminating the need for AF closure. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2460–2468, 2018.

     

Calcification in human intervertebral disc degeneration and scoliosis

Calcification is a pathological process that may lead to impairment of nutrient supply and disc metabolism in degenerative and scoliotic intervertebral discs (IVDs). The purpose of this study was to assess the calcification potential of IVDs in degenerative disc disease (DDD) and adolescent idiopathic scoliosis (AIS). For this purpose, 34 IVDs from 16 adult patients with DDD and 25 IVDs from 9 adolescent patients with AIS were obtained at surgery. The concave and convex parts of the scoliotic discs were analyzed separately. Von Kossa staining was performed to visualize calcium deposits, while type X collagen (COL X) expression associated with endochondral ossification was measured by immunohistochemistry. Alkaline phosphatase activity and calcium and inorganic phosphate concentrations were used as indicators of calcification potential. Results showed the presence of calcium deposits and COL X in degenerative and scoliotic IVDs, but not in control discs, and the level of the indicators of calcification potential was consistently higher in degenerative and scoliotic discs than in control discs. The results suggest that disc degeneration in adults is associated with ongoing mineral deposition and that mineralization in AIS discs might reflect a premature degenerative process. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 29:1888–1895, 2011     

Long‐Term Pathology of Ovine Lumbar Spine Degeneration Following Injury Via Percutaneous Minimally Invasive Partial Nucleotomy

The focus of this work is to assess the long‐term progression of degeneration in the ovine lumbar spine following a minimally invasive model injury comparable to the damage of an intervertebral disc (IVD) herniation. A partial nucleotomy was performed on 18 sheep via the percutaneous dorsolateral approach. The animals were culled at 6 and 12 months to evaluate the damaged and neighboring functional spine units (FSUs) for degenerative characteristics via μ‐CT and histology. Both quantitative μ‐CT and histology investigations demonstrated statistically significant differences between the native and damaged FSUs investigated. Qualitative analysis of μ‐CT revealed numerous pathological markers consistent with intervertebral disc degeneration (IDD), with differences in frequency and severity between the native and damaged FSUs. The annulus fibrosus reforms a pressure seal within 6 weeks, but the extent of the trauma is significant enough to initiate IVD degeneration, which is already clearly visible at 6 months and especially so 12 months post‐op. IDD pathology consistent with signs of a herniation was seen in both the 6‐ and 12‐month groups. This technique provides a useful model injury for the preclinical evaluation of IDD in large animal models, especially in regards to simulating disc herniation as well as for testing the efficacy of associated therapies in the future. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2376–2388, 2019     

骨质疏松患者基因多态性与椎间盘退变的相关性研究

目的 探讨分析骨质疏松患者基因多态性与椎间盘退变的相关性研究.方法 通过GEO数据库获取骨质疏松症(osteoporosis,OP)与椎间盘退变(intervertebral disc degenerative,IDD)的基因表达谱数据,分析两者的差异基因并取交集,再利用Cytoscape软件构建PPI网络,根据度值筛...     

Micro-RNA与椎间盘退行性变的研究进展

下腰疼痛正在成为目前影响人们生活质量的重要因素,其发病的年龄越来越趋于年轻化,每年因下腰痛带来的社会经济损失巨大。椎间盘退变(intervertebral disc degeneration,IDD)是引起下腰疼的重要原因,在多重因素作用下,椎间盘组织出现生物力学和结构的变化,发生纤维环破裂、髓核组织突出,使脊髓和神经根受压,从而引起患者出现下腰疼。微小RNA(Micro-RNA,miRNA)是一类长度为18~24个核苷酸序列的单链非编码小分子RNA,其在真核生物中广泛存在,作为基因表达的重要调控分子之一,已被证明在许多种疾病起始及进展阶段发挥着关键作用,故认为其可能在椎间盘退变中也发挥着重要的作用。目前,临床上针对IDD的治疗手段主要以手术治疗缓解临床症状为主,即使当前手术治疗可以取得良好的疗效,但是手术治疗会给患者带来更大的身体创伤和经济负担。miRNA在椎间盘退变过程中的作用是当前学术界研究的热点之一,研究表明miRNA在退变的椎间盘组织中呈现异常的表达模式,参与IDD的多种病理过程。目前,一些miRNA已被证明与椎间盘退变过程中的多种病理过程有关,包括髓核细胞凋亡和增殖、细胞外基质的降解、细胞自噬、炎症反应及软骨终板的退变等。基因芯片对比研究显示一些miRNA在退变髓核细胞中的表达与正常髓核细胞存在明显差异,这些差异表达的miRNA通过调控其各自的上、下游通路可能参与髓核细胞退变的进程,调控通路多有交叉并行,构建出一个庞大的miRNA调控网。了解miRNA在发病过程中的靶基因和机制,能够在疾病的起源、发展和预后等方面提供重要参考。因此,综述了miRNA在椎间盘退变过程中的重要作用和潜在的临床治疗意义。随着对miRNA研究的深入,通过了解椎间盘退变的分子生物学机制,可以为IDD的诊断和治疗提供新思路,非常有可能成为IDD生物学治疗的新策略。     

Differential effects of nicotine and tobacco smoke condensate on human annulus fibrosus cell metabolism

Tobacco smoking increases the risk of intervertebral disc degeneration (IDD) and back pain, but the mechanisms underlying the adverse effects of smoking are largely unknown. Current hypotheses predict that smoking contributes to IDD indirectly through nicotine‐mediated vasoconstriction which limits the exchange of nutrients between the discs and their surroundings. We alternatively hypothesize that direct contact of disc cells, that is, cells in the outermost annulus and those present along fissures in degenerating discs, with the vascular system containing soluble tobacco smoking constituents could perturb normal metabolic activities resulting in IDD. In this study, we tested our hypothesis by comparing the effects of direct exposure of human disc cells to tobacco smoke condensate and nicotine on cell viability and metabolic activity. We showed that smoke condensate, which contains all of the water‐soluble compounds inhaled by smokers, exerts greater detrimental effects on human disc cell viability and metabolism than nicotine. Smoke condensate greatly induced an inflammatory response and gene expression of metalloproteinases while reduced active matrix synthesis and expression of matrix structural genes. Therefore, we have demonstrated that disc cell exposure to the constituents of tobacco smoke has negative consequences which have the potential to alter disc matrix homeostasis. © 2011 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29: 1585–1591, 2011     

Accelerated aging of intervertebral discs in a mouse model of progeria

Intervertebral disc degeneration (IDD) is a common and debilitating disorder that results in reduced flexibility of the spine, pain, and reduced mobility. Risk factors for IDD include age, genetic predisposition, injury, and other environmental factors such as smoking. Loss of proteoglycans (PGs) contributes to IDD with advancing age. Currently there is a lack of a model for rapid investigation of disc aging and evaluation of therapeutic interventions. Here we examined progression of disc aging in a murine model of a human progeroid syndrome caused by deficiency of the DNA repair endonuclease, ERCC1–XPF (Ercc1^?/Δ mice). The ERCC1‐deficient mice showed loss of disc height and degenerative structural changes in their vertebral bodies similar to those reported for old rodents. Compared to their wild‐type littermates, Ercc1^?/Δ mice also exhibit other age‐related IDD characteristics, including premature loss of disc PG, reduced matrix PG synthesis, and enhanced apoptosis and cell senescence. Finally, the onset of age‐associated disc pathologies was further accelerated in Ercc1^?/Δ mice following chronic treatment with the chemotherapeutic agent mechlorethamine. These results demonstrate that Ercc1^?/Δ mice represent an accurate and rapid model of disc aging and provide novel evidence that DNA damage negatively impacts PG synthesis. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:1600–1607, 2010     

The Mechanisms and Functions of GDF‐5 in Intervertebral Disc Degeneration

Intervertebral disc degeneration (IDD) is widely recognized as the main cause of low back pain, which leads to disability in aging populations and induces great losses both socially and economically worldwide. Unfortunately, current treatments for IDD are aimed at relieving symptoms instead of preserving disc structure and function. Researchers are forged to find new promising biological therapeutics to stop, and even reverse, IVD degeneration. Recently, the injection of growth factors has been shown to be a promising biological therapy for IDD. A number of growth factors have been investigated to modulate the synthesis of the extracellular matrix (ECM) through a variety of pathogenetic biological mechanisms, including suppressing inflammatory process and down‐regulating degrading enzymes. However, growth factors, including Transforming Growth Factor‐β (TGF‐β), Fibroblast Growth Factor (FGF), and Insulin‐like Growth Factor‐1 (IGF‐1), may induce unwanted blood vessel in‐growth, which accelerates the process of IDD. On the contrary, studies have demonstrated that injection of GDF‐5 into the intervertebral disc of mice can effectively alleviate the degeneration of the intervertebral disc, which elicits their response via BMPRII and will not induce blood vessel in‐growth. This finding suggests that GDF‐5 is more suitable for use in IDD treatment compared with the three other growth factors. Substantial evidence has suggested that GDF‐5 may maintain the structure and function of the intervertebral disc (IVD). GDF‐5 plays an important role in IDD and is a very promising therapeutic agent for IDD. This review is focused on the mechanisms and functions of GDF‐5 in IDD.