机械应力因素在脊柱韧带骨化发生机制中的作用研究进展

正脊柱韧带骨化是一种以脊柱正常韧带发生异位骨化为特点的慢性、退行性疾病。主要包括后纵韧带骨化(OPLL)、黄韧带骨化(OLF)及弥漫性特发性骨肥大症(DISH)~([1])。后纵韧带和黄韧带解剖位置特殊,直接参与椎管结构的组成,因此,OPLL和OLF的发生常常导致脊髓和神经根受压,引起严     

脊柱韧带骨化机制的分子生物学研究进展

脊柱韧带骨化（ossification of the spinal ligament,OSL）是一种引起异位骨形成及继发的不同程度神经性功能受损的病理状态,以多种脊柱韧带的骨化为特征,包括后纵韧带骨化（ossification of the posterior longitudinal ligament,OPLL）、黄韧带骨化（ossification of the ligamentum flavum,OLF）和弥漫性特发性骨质增生（diffuse idiopathicskeletal hyperostosis,DISH）,常引起脊髓病变、神经根病变或同时累及两者。对于OSL的致病原因仍不明确。OSL是一个多因素导致的疾病,包括多种基因和环境因素相互作用,目前相关研究认为：遗传、内分泌与代谢、生长因子、机械应力、微量元素、脊柱变性、创伤和炎症等因素可能参与其中,本文就其发病机制的相关分子生物学研究现状做一综述。     

脊柱后纵韧带骨化性疾病的基础研究进展

脊柱后纵韧带骨化（ossification of posterior longitudinal ligament,OPLL）是指脊柱后纵韧带发生病理性异位骨化,多见于颈椎,常独立或合并其他病变对脊髓神经根形成压迫。在年龄≥65岁的亚洲人群中发病率可达20％～34％。日本学者对该病研究较多,目前的研究表明OPLL是一种基于多基因与环境等其他因素相关的复杂疾病,具体发病机制不明。近年来,对OPLL的基础研究随着生物科学技术的发展取得了一些进展,本文就OPLL的基础研究进展作如下综述。     

脊柱后纵韧带骨化症病因学研究进展

后纵韧带骨化症(OPLL)是脊柱外科常见病之一.附着于椎体后缘的后纵韧带在多因素作用下形成骨化物,骨化物持续生长造成脊髓和神经根受压,平时可无症状或症状不典型,一旦遇到外伤,即使是轻微外力也可导致严重的四肢感觉、运动、反射及二便功能障碍,甚至瘫痪,严重降低患者生活质量,给家庭及社会带来沉重负担.OPLL在东亚地区高发,...     

胸椎后纵韧带骨化症的研究进展

后纵韧带骨化症（ossification of the posterior longitudinal ligament,OPLL）是脊柱后纵韧带进行性异位骨化压迫脊髓和神经根而导致其功能受损的一种疾病,是日本及其他东亚国家颈胸段脊髓病和神经根病的常见原因之一,多发于颈椎,胸椎次之。     

脊柱后纵韧带骨化及黄韧带骨化的易感基因研究进展

脊柱后纵韧带骨化(ossification of posterior longitudi-nal ligamentum,OPLL)及黄韧带骨化(ossification of theligamentum flavum,OLF)均为发生于脊柱韧带的疾病,是导致颈胸部椎管狭窄、脊髓压迫的常见原因。外界因素及易感基因是影响OPLL与OLF发病率的重要原因。外界致病因子如慢性退行性变,内分泌和代谢性疾病,身高/体     

遗传因素在后纵韧带骨化症发生机制中的作用

后纵韧带骨化症（ossification of the posterior longitudinal ligament,OPLL）是指脊柱后纵韧带发生异位骨化,骨化物压迫脊髓和神经根后出现神经功能损害症状的疾病.该病常见于颈椎,在亚洲中老年人群中高发,男性多见,可与其他脊柱退行性病变并存[1].目前认为OPLL是由多种因素共同引起,如遗传、代谢异常及机械应力刺激等.本文就OPLL遗传基因研究做一归纳,并阐述了在机械应力环境下易感基因对OPLL发病的影响;此外,本文又简述了微RNA（microRNA, miRNA）在调节OPLL易感基因成骨表达方面的研究进展,以便探讨遗传因素（OPLL易感基因及miRNA）在OPLL发生机制中的作用.     

骨代谢相关基因单核甘酸多态性在脊柱后纵韧带骨化发生中的作用

脊柱韧带骨化症是以后纵韧带骨化(ossification of the posterior longitudinal ligament,OPLL)与黄韧带骨化为代表的临床常见病,其发病机制尚不清楚[1～4]。该病呈进展性,可导致脊髓压迫及神经功能障碍。随着分子生物学的发展及基因研究的深化,发现该病具有显著的遗传倾向,考虑为多基因单核甘酸多态性位点变异为特征的家族病。     

肥胖导致男性不育的表观遗传机制研究进展

肥胖引发表观遗传改变可导致男性出现不育表型。关于肥胖与男性不育的关系问题,早期研究多集中于内分泌方面。近年研究发现肥胖还可以引发机体表观遗传改变,如DNA甲基化,残余组蛋白修饰,小RNA等,影响精子成熟发育。DNA甲基化是胞嘧啶-磷酸-鸟嘌呤二核苷酸的胞嘧啶残基上的调节标记,肥胖导致DNA甲基化异常,并改变mRNA表达丰度,还可以影响印记基因表达出现印记基因病。残余组蛋白修饰方式包括甲基化、乙酰化等,它们可以相互作用或协同作用,以保证精子正常生长发育。肥胖可以改变甲基化酶及乙酰化酶活性,直接影响残余组蛋白的甲基化和乙酰化;还可以影响精子小RNA的表达,导致精子缺陷。本文就肥胖引起的表观遗传学改变及导致男性不育的作用机制做逐一综述。     

微RNA在颈椎后纵韧带骨化症中的作用和机制研究进展

<正>颈椎后纵韧带骨化症(OPLL)是附着于椎体后缘的后纵韧带在多因素作用下发生异常增厚和骨化的现象,是常见的颈椎退行性疾病之一,可导致严重的感觉和运动功能障碍^[1]。目前,OPLL的发生机制尚不清楚,其早期诊断和治疗方式仍然有限。有文献^[1]报道,遗传与环境因素共同参与了OPLL的发生。目前已知有多个基因(COL6A1、COL6A6、TLR1、FGFRI、BMP2、Runx2等)与OPLL的发生、发展有关^[2-4],涉及的相关信号通路,包括转化生长因子β/骨形态发生蛋白(TGF-β/BMP)、c AMP/PKA、MAPK、Wnt、JAK/STAT、Pi3k/Akt等^[5-10]。     

脊柱韧带骨化性疾病发病机制的研究进展

<正>脊柱韧带骨化性疾病是一类临床常见的多因素迟发性疾病,起病隐匿,常引起脊髓和神经根病变,以多种脊柱韧带骨化为特征,包括后纵韧带骨化(ossification of the posterior longitudinal ligament,OPLL)、黄韧带骨化(ossification of the ligamentum flavum,OLF)和弥漫性特发性骨肥大症(diffuse idiopathic skeletal hyperostosis,DISH)[1]。亚     

血管疾病的表观遗传学研究进展

表观遗传学指独立于DNA核苷酸序列本身的基因表达的可遗传改变,其主要机制包括DNA甲基化、组蛋白修饰和非编码RNA等,这些机制共同作用调控基因的特异性表达。血管疾病是由环境因素和遗传因素相互作用引发的一种慢性疾病。近年来,越来越多的研究证实表观遗传调节在血管疾病的发生发展中具有重要的作用。本文对表观遗传学在血管疾病中的最新研究进展进行综述。     

Drug therapy targeting pyrophosphate slows the ossification of spinal ligaments in twy mice

The lack of an effective drug therapy against ossification of spinal ligament (OSL) warrants investigation into the therapeutic target of this disease. An endogenous inhibitor of biomineralization, pyrophosphate (PPi) is a potential therapy for ectopic ossification; however, exogenous PPi is rapidly hydrolyzed by tissue non‐specific alkaline phosphatase (TNAP) present in body fluids. In this study, we examined whether a drug therapy targeting PPi is efficacious for the treatment of OSL using the Enpp1^ttw/ttw (twy) mouse model. Twenty male twy mice were randomized into four groups: (i) vehicle (Control); (ii) alkaline phosphatase inhibitor levamisole (5 mg/kg/day sc continuously); (iii) levamisole + exogenous PPi (160 µmol/kg/day sc continuously); and (iv) nuclear retinoic acid receptor‐γ (RARγ) agonist (6 µg/kg sc daily). The RARγ agonist, which is a proven inhibitor of ectopic endochondral ossification, was used as a positive control. Treatments commenced when the mice were 5 weeks of age and continued for 4 weeks. Longitudinal micro‐computed tomography and postmortem histological analysis were performed. Administration of levamisole alone and in combination with PPi increased serum PPi concentration by 17% and 52%, respectively, compared to that in vehicle‐treated mice. The development of OSL in twy mice was suppressed by levamisole + PPi and RARγ agonist treatments, but not by levamisole alone. The levamisole + PPi therapy did not cause osteoporosis, whereas RARγ agonist‐treated mice developed osteoporosis. Treatment of twy mice with levamisole in combination with exogenous PPi increased serum PPi level, which slowed the progression of OSL without producing adverse effect on bone. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1256–1261, 2018.

     

Experimental study on ossification of spinal ligaments in the rabbit under influence of bone morphogenetic protein

Bone morphogenetic protein (BMP) is known to induce cartilage from mesenchymal cells in organ culture. The purpose of the present study was to determine whether spinal ligaments differentiate into cartilage when cultured with BMP. Implantation of BMP into the yellow ligament was also done to make a model of the ossification of yellow ligament. The rabbit was employed as an experimental animal. In organ culture, BMP induced new cartilage from the posterior longitudinal ligament, the yellow ligament and the supraspinous ligament. This indicates that spinal ligaments have the potential to ossify, and bone or periosteum may not have a direct relationship with spinal ligament ossification. Ossification of the yellow ligament was produced by implantation of BMP. Blood vessels are thought to have some role in the ossification of spinal ligaments. The spinal cord was compressed posteriorly by the ossified yellow ligament. This ossification of the yellow ligament resembled that of human beings and may be regarded as a useful experimental model.     

Orthotopic ossification of the spinal ligaments of zucker fatty rats: A possible animal model for ossification of the human posterior longitudinal ligament

Ossification of the posterior longitudinal ligament is a human genetic disease in which pathological ectopic ossification of the spinal ligaments develops. This leads to myelopathy or radiculopathy due to compression of the spinal cord. In this study, we investigated the histological features of orthotopic ossification of the spinal ligaments of senile Zucker fatty rats. A remarkably high incidence of orthotopic ossification was observed mainly in the thoracic spinal ligaments as compared with controls. The histopathological findings were similar to those for ossification of the human posterior longitudinal ligament. Bone morphogenetic proteins and activins, which exert their effects by way of specific type-I and type-II serine/threonine kinase receptors, play important roles in the formation of bone and cartilage. In the spinal ligaments of Zucker fatty rats, bone morphogenetic protein receptors and activin receptors were immunohistochemically detected around the ossified foci in a manner similar to that previously shown for the ossified tissue from patients who had ossification of the posterior longitudinal ligament. Thus, bone morphogenetic proteins and activin receptors might play important roles in orthotopic ossification of the spinal ligaments of Zucker fatty rats as well as in ossification of the posterior longitudinal ligament of humans. In addition, bone morphogenetic protein-receptor-IA was expressed in the nonossified ligament, suggesting that the spinal ligaments of the rats may have a predisposition to orthotopic ossification. In the controls, no expression of bone morphogenetic protein receptors or of activin receptors was observed. In conclusion, there is a great degree of similarity between orthotopic ossification of the spinal ligaments of Zucker fatty rats and ossification of the posterior longitudinal ligament of humans. Thus, the rats provide a useful animal model for the study of ossification of the human posterior longitudinal ligament.     

异位骨化发病机制的研究进展

目的总结异位骨化(heterotopic ossification,HO)发病机制的研究进展。方法查阅近年有关HO危险因素及发病机制的文献,并综合分析。结果 HO发病机制尚未明确,但对HO相关的细胞外因子、信号通路、转录因子等有了更深入了解,如BMP、Smad信号通路、核心结合因子α1/成骨特异性转录因子2等可能参与了HO的形成,而一些相关的微小RNA也有可能参与HO形成。结论通过对HO发病机制进一步研究,为有效防治HO奠定基础。