H型血管在改善骨丢失中的作用机制研究进展

在骨骼系统中, 血管生成与骨形成之间的耦联作用可促进骨骼生长及维持骨量平衡。H型血管(CD31hiEmcnhi)是一类骨特异性毛细血管亚型, 实质为血管内皮细胞, 主要分布于骨干骺端, 周围密布骨祖细胞, 介导成血管-成骨耦联机制, 其中涉及多种细胞因子及信号通路, 包括血小板源性生长因子BB、轴突导向分子3、低氧诱导因子-1α、Notch信号通路、血管内皮生长因子等。H型血管通过多种细胞因子传递信号, 增强血管生成和骨形成间的联系, 从而调控骨生长和骨稳态;靶向增加H型血管数量可用于治疗骨丢失, 为临床骨损伤修复和抗骨质疏松治疗提供参考。     

骨关节炎骨软骨损伤修复的研究现状

[目的]综述骨关节炎骨软骨损伤修复的难点及研究进展。[方法]通过检索Pub Med数据库,分析总结近5年骨软骨再生及修复的相关文献。[结果]由于软骨下骨硬化、骨软骨界面的完整性破坏以及新生血管形成,骨关节炎的关节软骨损伤加重,同时滑膜炎时炎症因子分泌增加,抗炎的生物治疗及抑制新生血管形成对于骨软骨修复颇有前景。另一方面,随着表观遗传学的发展及软骨细胞能量代谢(缺氧诱导因子-1α)与全身代谢尤其是过氧化物酶体增殖物激活受体的研究促进了骨软骨损伤的机制研究。利用脂肪干细胞及内源性细胞归巢为骨软骨损伤修复提供了新思路,但仍面临着软骨细胞老化的难题。[结论]骨软骨再生目前比较成熟,而在体内试验时,骨软骨微环境难以维持并且软骨老化,不能长时间维持软骨生物学功能是目前骨软骨修复最大的挑战。     

骨H型血管生成机制及影响因素的研究现状

骨血管在骨生长、重塑和损伤修复中发挥重要作用,H型血管是一类同时高表达CD31与Emcn的骨血管亚型,具有显著的解剖特征与年龄依赖性减少特点,深度参与血管生成与骨形成之间的偶联。一些细胞因子如缺氧诱导因子1α、血管内皮生长因子A、血小板衍生生长因子BB、神经轴突导向因子3等可参与调控H型血管的生成,同时药物治疗、物理治疗和转移性肿瘤也能对H型血管产生影响。本文通过回顾近年文献,总结H型血管生成的分子机制与影响因素,以期为骨折不愈合、骨代谢异常等骨病的治疗提供新思考。     

高糖对骨髓间充质干细胞作用机制的研究进展

骨髓间充质干细胞的功能改变与功能障碍是糖尿病性骨质疏松病态骨代谢模式的根本原因。在长期高糖环境下,骨髓间充质干细胞生物活性及功能特性发生紊乱。具体表现为：高糖会促进骨髓间充质干细胞的凋亡、自噬、铁死亡及成脂向分化,抑制其旁分泌及成血管向分化,但在细胞增殖、定向迁移及成骨向分化方面仍存在一定争议。因此,深入研究高糖对骨髓间充质干细胞的作用机制,有利于突破糖尿病性骨质疏松症干细胞疗法的局限性,挖掘潜能优势。     

骨微损伤形成与修复机制的研究进展

骨微损伤是在光学显微镜下能够观察到的骨基质损害,骨微损伤的产生、发展与疲劳载荷有关,骨微损伤能够启动骨重建来进行修复,但不同微损伤类型对骨重建的影响不同。骨微损伤有五种类型,目前研究多集中在线性微裂纹与弥散性微损伤,它们具有完全不同的形态特征和修复方式。本文通过对骨微损伤的分类、检测方法、形成及修复机制进行综述,深入研究神经肽对骨重建的作用,旨在进一步探讨骨微损伤的修复机制,为骨质疏松性骨折的防治奠定基础。     

Ｈ 型血管在骨发育及骨疾病中作用研究进展

骨髓中的Ｈ 型血管是与成骨活动高度耦联的骨髓血管亚型,特点是ＥＭＣＮ 和ＣＤ３１ 的高表达。Ｈ 型血管在长骨发育的 过程中在松质骨区形成,为生长板附近的细胞提供充足的营养支持,并通过旁分泌的方式影响前成骨细胞及破骨细胞的增殖 及分化,提供适宜的微环境从而有利于新生骨的形成。由于Ｈ 型血管与成骨活动有十分密切的关系,在骨折愈合、骨质疏松、 骨关节炎、骨坏死以及肿瘤骨转移等骨疾病生理和病理过程中均有Ｈ 型血管的参与,而针对Ｈ 型血管的治疗可以改善上述疾 病的进程。本文对Ｈ 型血管与其耦联的成骨活动的机制进行了综述,有利于进一步了解Ｈ 型血管在骨代谢中的作用,为从血 管的角度理解骨疾病提供理论基础和思路。     

铁死亡调控在骨质疏松症中的作用机制及中药干预研究

骨质疏松症作为常见的代谢疾病,发病率逐年增加,危害性大,但常用的抗骨质疏松药物副作用较大,不利于长期服用。铁死亡是以活性氧异常增多、铁代谢异常及脂质过氧化积累作为主要特征的新型细胞死亡方式。研究表明铁死亡与骨质疏松的发生发展相关,会破坏骨稳态,导致骨质疏松症的发生,现已成为骨质疏松领域的新研究热点。中医药作为我国的文化瑰宝,不少研究表明中药及其活性成分对骨质疏松相关的细胞铁死亡具有调控作用,对骨质疏松症的防治具有独特优势。因此,本文汇总了国内外关于调控铁死亡防治骨质疏松症的作用机制及中药干预的最新文献, 旨在从铁死亡角度为中医药防治骨质疏松症提供新的研究思路。     

铁死亡在骨关节炎发生机制和治疗中的研究进展

骨关节炎是以软骨退行性变为主要特征的常见疾病,其发病机制复杂,严重影响中老年人的生活质量。铁死亡作为近年来发现的一种新形式的调节性细胞死亡方式,其发生机制涉及氨基酸、铁、脂质过氧化的密切合作,以及多种通路,如传统GPX4依赖性通路、FSP1-CoQ10-NAD(P)H通路、DHODH-CoQ10H2通路、GCH1-BH4通路、角鲨烯介导通路均可抑制铁死亡的发生。近年来大量研究证明,骨关节炎中存在铁死亡。该文拟从铁死亡在骨关节炎中的发生机制以及相关治疗通路进行综述,以期为骨关节炎的治疗提供新思路。     

微循环与骨质疏松的关系

骨质疏松主要与绝经、老龄以及某些影响骨代谢的疾病或药物有关,在骨代谢上主要表现为破骨细胞与成骨细胞功能的失衡。而骨骼主要由支配它的血管来完成新陈代谢,如果支配它的微循环出现障碍,是否会影响骨代谢以及是否会导致骨质疏松?国内相关方面研究较少。国外研究认为,从细胞分子方面而言,骨细胞能够产生血管生成因子,而血管内皮可以产生成骨因子,血管网的增长由软骨细胞和骨细胞产生的信号因子调控,同时,血管也具有影响新骨的成骨作用,血管生成和成骨通过CD31及Emcn抗体强阳性的H型血管内皮细胞相耦合。动物实验发现,骨质疏松的大鼠其微血管数量和VEGF较正常对照组明显减少,运动组的大鼠骨和骨髓血流量与股骨骨小梁体积分数(BV/TV)增加相关;临床实验中通过对腰椎的CT动态增强扫描灌注成像及BMD检查发现微循环与骨密度的变化规律一致,由此推测微循环灌注障碍是骨密度流失和加速IDD(椎间盘退变)的潜在原因。本文将从分子生物、动物实验到临床观察方面将国外有关研究进展做一介绍。     

铁蓄积、骨内血管与骨质疏松关系的研究进展

铁蓄积可能是骨质疏松症发生的独立危险因素,许多研究表明铁蓄积可导致骨质疏松症的发生。目前,骨内血管是骨质疏松研究的热点,骨中特殊的血管亚型偶联了骨形成与血管形成。那么,铁蓄积能否通过影响骨内特殊血管亚型,进而引起骨量下降?本文就铁蓄积与血管的关系作一综述,探讨铁与骨内血管调控骨代谢的潜在意义。     

The coexistence and characteristics of osteoarthritis and osteoporosis

We defined the clinical features and radiographic coexistence of osteoarthritis and osteoporosis in fifty women with primary coxarthrosis and fifty age-matched women (average age, 69 +/- 5 years) with idiopathic osteoporosis. The patients with osteoarthritis had undergone total hip replacement. The diagnosis of primary osteoarthritis was established by clinical, radiographic, and histological criteria, and the diagnosis of osteoporosis was confirmed by histomorphometric analysis of specimens taken at iliac-bone biopsy. In the arthritic patients, spinal osteoporosis was identified by radiographic evidence of compression fractures, kyphosis, and scoliosis. Femoral osteoporosis was demonstrated by the index of Singh et al. and the femoral canal-shaft ratio. In the osteoporotic patients coxarthrosis was measured radiographically by the scale of Kellgren and Lawrence. On the average, the osteoporotic patients were twelve kilograms lighter than the osteoarthritic patients. Fifty-eight per cent of the osteoporotic and 18 per cent of the osteoarthritic patients had a scoliotic curve of at least 10 degrees. The prevalence of osteoarthritis of the hip in the osteoporotic women was 4 per cent, and the prevalence of compression fractures in the arthritic women was 6 per cent, which was approximately one-quarter of the expected incidence. These results show that: (1) osteoporosis does not protect against the development of coxarthrosis, (2) coxarthrosis is a negative risk factor for osteoporotic compression fractures, and (3) scoliosis and an ectomorphic habitus are clinical markers that identify a risk for osteoporosis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Osteoporosis and vitamin-D deficiency among postmenopausal women with osteoarthritis undergoing total hip arthroplasty

BACKGROUND: Several epidemiological studies have shown a lower prevalence of osteoporotic hip fractures in patients with osteoarthritis. Other studies have demonstrated elevated bone mineral density in patients with osteoarthritis. The prevailing view is that there may be an inverse relationship between osteoarthritis and osteoporosis. The purposes of the present study were to describe a subgroup of patients with osteoarthritis who were found to have osteoporosis and to assess the vitamin-D status and other risk factors for low bone density in osteoarthritic subjects with and without osteoporosis. METHODS: The bone mineral density of the spine, the proximal part of the femur, and the total body was measured with dual-energy x-ray absorptiometry in sixty-eight postmenopausal white women who were scheduled to undergo total hip replacement for advanced osteoarthritis. The serum levels of 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, intact parathyroid hormone, osteocalcin, and bone-specific alkaline phosphatase and the urinary level of N-telopeptide were measured. Information from validated lifestyle, dietary, and demographic questionnaires was also evaluated. RESULTS: Seventeen (25%) of the sixty-eight women had occult osteoporosis (as indicated by a T score of less than -2.5). Fifteen (22%) of the sixty-eight subjects had vitamin-D deficiency, and three (4%) had an elevated serum parathyroid hormone level. Only two of the seventeen osteoporotic women had vitamin-D deficiency. On the basis of these numbers, vitamin-D status was not correlated with bone density (p = 0.32). Analysis of the relationship between the number of years since menopause and osteoporosis or markers of elevated bone turnover showed that osteoporosis was detected throughout the postmenopausal period. CONCLUSION: A substantial portion of these sixty-eight white women with osteoarthritis of the hip had occult osteoporosis and hypovitaminosis D. Vitamin-D deficiency was not restricted to the group with low bone density. These results support the need to consider the presence of both osteoporosis and vitamin-D deficiency in women with advanced osteoarthritis.     

铁死亡与骨质疏松

骨质疏松是一种代谢性疾病,以骨量减少和骨骼微结构的破坏为特点,常导致骨折的发生。铁死亡作为2012年新发现的细胞程序性死亡,其主要的特征是铁过载和ROS的积累,从而导致脂质过氧化的发生。近来,越来越多的研究表明铁死亡在骨质疏松中扮演着重要作用,因此,本文就铁死亡在骨质疏松中的最新研究进展进行综述。     

Micro-CT and mechanical evaluation of subchondral trabecular bone structure between postmenopausal women with osteoarthritis and osteoporosis

Summary  

An inverse relationship between osteoarthritis and osteoporosis has been debated over years. The microstructure of the femoral heads from postmenopausal osteoarthritic and osteoporotic women was evaluated with micro-CT. Significant differences were observed in microstructural parameters between them. Different microstructure might relate to the opposite bone defects in osteoarthritis and osteoporosis.     

Fracture healing in osteoporotic fractures: is it really different? A basic science perspective

Osteoporosis is a major health problem characterized by compromised bone strength that predisposes patients to an increased risk of fracture. Osteoporotic patients differ from normal subjects in bone mineral composition, bone mineral content, and crystallinity. Poor bone quality in patients with osteoporosis presents the surgeon with difficult treatment decisions. Much effort has been expended on improving therapies that are expected to preserve bone mass and thus decrease fracture risk. Manipulation of both the local fracture environment in terms of application of growth factors, scaffolds and mesenchymal cells, and systemic administration of agents promoting bone formation and bone strength has been considered as a treatment option from which promising results have recently been reported. Surprisingly, less importance has been given to investigating fracture healing in osteoporosis. Fracture healing is a complex process of bone regeneration, involving a well-orchestrated series of biological events that follow a definable temporal and spatial sequence that may be affected by both biological factors, such as age and osteoporosis, and mechanical factors such as stability of the osteosynthesis. Current studies mainly focus on preventing osteoporotic fractures. In recent years, the literature has provided evidence of altered fracture healing in osteoporotic bone, which may have important implications in evaluating the effects of new osteoporosis treatments on fracture healing. However, the mechanics of this influence of osteoporosis on fracture healing have not yet been clarified and clinical evidence is still lacking.     

基于WNT16预防骨质疏松非椎体骨折的研究进展

随着我国老龄化程度加深,骨质疏松发病率持续升高,已经严重威胁我国国民健康。骨折作为骨质疏松最严重的并发症,是骨质疏松患者死亡的主要原因。近年来,关于骨质疏松骨折的研究有很多,但偏重于骨质疏松椎体骨折,而骨质疏松非椎体骨折的研究较少。目前,市场上预防骨质疏松的药物也往往针对椎体骨折,而骨质疏松非椎体骨折的可用药物较少。WNT信号通路在预防骨质疏松骨折方面的研究较多,WNT16作为WNT家族中新成员,是调控骨皮质的关键因子,骨质疏松非椎体骨折的关键原因在于骨皮质变薄,因此,WNT16可能是预防非椎体骨折的潜在靶标。本文主要通过总结近期关于WNT16在骨质疏松骨折上的研究,探讨WNT16在骨质疏松非椎体骨折的预防上所起的作用,为临床预防骨质疏松非椎体骨折提供参考,以及为骨质疏松非椎体骨折药物开发提供新思路。     

Evidence that type I osteoporosis results from enhanced responsiveness of bone to estrogen deficiency

Type I osteoporosis occurs within 20 years after menopause and is associated with excessive cancellous bone loss and fractures of the vertebrae and distal radius. We have suggested that it may be caused by estrogen deficiency plus some additional factor predisposing to excessive bone loss. One such factor might be a greater degree of sex steroid deficiency, a possibility that could not be previously excluded because assays of sufficient sensitivity have only recently become available. Thus, we studied 36 women with vertebral fractures due to typical high turnover type I postmenopausal osteoporosis and 36 normal postmenopausal women using new ultrasensitive assays with detection limits of 1 pg/ml for estradiol, 5 pg/ml for estrone and 5 ng/dl for testosterone to test if type I osteoporosis results from enhanced responsiveness of bone to estrogen deficiency. Mean levels of serum sex steroids were identical in both groups, but bone turnover was increased by up to 55% in the women with type I osteoporosis. Moreover, compared with controls, the osteoporotic women had a 51% higher (P<0.01) serum osteoprotegerin level, which was likely a compensatory response to the increased bone turnover. In the osteoporotic women, 1-year treatment with transdermal estrogen in 14 women reduced total deoxypyridinoline, an index of bone resorption, by 58% as compared with placebo treatment in 17 women (P<0.001). Thus, as compared to controls, postmenopausal osteoporotic women had comparable sex steroid levels but higher bone turnover levels that were responsive to estrogen therapy. This is consistent with the hypothesis that the greater bone loss in type I osteoporosis is the result of impaired responsiveness of bone to low postmenopausal levels of sex steroids.     

H亚型血管与骨质疏松症

目前,骨质疏松症的传统治疗方法主要集中于抑制骨破坏和促进骨形成方面,但此单一的治疗方法很难彻底解决多重因素致病的骨质疏松症。近来,许多文献报道血管形成与骨形成之间存在偶联关系,其中骨骼中新发现的H亚型血管成为骨质疏松治疗的新焦点。根据骨骼血管内皮细胞位置和功能的区别,可分为H亚型血管和L亚型血管,而H亚型血管可促进其周围骨祖细胞的分化与增殖。H亚型血管主要分布于干骺端和骨膜下,表现为血小板-内皮细胞粘附分子抗体(CD31)和内皮粘蛋白抗体(endomucin,EMCN)强阳性;而L亚型血管表现为两种内皮细胞抗体(CD31或EMCN)弱阳性,分布于骨干区。实验表明,H亚型内皮细胞与周围的骨祖细胞数量会随着小鼠的老龄化呈正比例下降,而且小鼠体内缺氧诱导型转录因子1α缺失后会出现H亚型内皮细胞和骨祖细胞数量明显降低,这些均提示H亚型血管与骨形成存在偶联关系。笔者着重对H亚型内皮细与骨形成之间存在的偶联关系及其机制进行综述,探讨H亚型内皮细胞与骨质疏松症的关系,以进一步加深对骨质疏松症发生、发展的认识,为骨质疏松症治疗提供新的思路与方法。     

H型血管在骨质疏松症中的研究进展

骨质疏松症是一种全身性骨病,具有骨微结构退化、骨密度低的特点,在世界范围内发病率较高。随着我国人口逐渐进入老龄化,骨质疏松症的发病率日益上升,已经成为威胁老年人群生活质量的重要因素,给公共卫生系统带来了难以预料的挑战。近年来,许多文献报道骨内特殊型血管——H型血管生成与骨生成之间存在耦合,为骨质疏松症的治疗提供了新的研究目标。本文就H型血管的结构及功能、参与H型血管生成与成骨的细胞因子以及其他因素做一综述。