雌激素与骨性关节炎

雌激素低于正常水平的绝经后妇女更易患骨性关节炎表明雌激素是骨性关节炎重要调节因子。已经证实正常和骨性关节炎关节软骨均存在雌激素受体（α受体和β受体），说明关节软骨是雌激素的靶组织。雌激素可以通过细胞因子和细胞生长因子等多种途径调节软骨细胞的功能，对雌激素影响软骨细胞代谢的可能机制也进行了动物实验研究。本文就雌激素在软骨细胞代谢中的作用和雌激素替代治疗进行综述。     

IL-22及RANKL在骨性关节炎患者中的表达及调节关系

目的 探究骨性关节炎患者体内细胞核因子-κB受体活化因子配体（Receptor activator of nuclear factor-κB ligand,RANKL）和白介素-22(Interleukin-22,IL-22)的表达差异和调节作用以及在骨性关节炎进程中诱导关节软骨退化的可能机制。方法 采用酶联免疫法检测骨性关节炎患者与正常人血清、关节液中的RANKL和IL-22;番红O-固绿复染观察骨性关节炎患者和正常人关节软骨的组织学改变,免疫组化检测关节软骨中RANKL和IL-22的表达情况;RT-PCR检测骨性关节炎患者和正常人关节软骨组织中RANKL、IL-22和基质金属蛋白酶3(Matrix metalloproteinase-3,MMP-3)等基因的表达水平;蛋白质印迹法检测骨性关节炎患者和正常人关节软骨中RANKL、IL-22和MMP3蛋白的含量。用不同浓度的重组人IL-22(Recombinant human IL-22,rhIL-22)处理体外培养的骨性关节炎患者和正常人的关节软骨细胞,采用RT-PCR检测干预后软骨细胞RANKL和MMP-3基因的表达水平。结果 骨性...     

骨性关节炎的代谢机制研究进展

以关节软骨为主的正常代谢在滑膜关节的功能维持中发挥着至关重要的作用。在骨性关节炎不良微环境下,为了维持能量稳态,关节软骨细胞以及关节其他一些组织细胞的代谢经历了由相对静止向高度激活状态的转变。这一现象导致具有致炎和促蛋白分解作用的中间代谢产物合成的增加,后者通过激活关键转录因子及信号通路而诱发炎性反应,进而促进软骨分解代谢,加速软骨退变进程。近年研究显示,代谢异常在炎症性关节疾病中发挥了重要作用,尤以骨性关节炎表现显著,许多骨性关节炎表型都伴有关节组织细胞代谢紊乱。本文着重介绍代谢异常在骨性关节炎病理中的作用,为探索骨性关节炎治疗方法及相关机制提供研究思路。     

创伤性关节炎发生机制相关性研究

创伤性关节炎发生机制研究显示,关节软骨凋亡或坏死引起关节软骨数量减少,导致关节软骨退变;关节生物力学及其关节周围环境应力改变引起关节软骨细胞及基质之间的动态平衡破坏,进一步引发关节软骨退变;关节损伤后关节液中细胞炎症介质对关节软骨的作用及介质之间相互作用在关节软骨退变中起着重要作用;关节损伤疾病发展过程及关节软骨代谢均与患者个体基因学关系密切。研究明确关节损伤后各种因素在创伤性关节炎中的作用及各种因素之间的联系,有助于更深入地了解创伤性关节炎的发生机制,更好地制定相关治疗方案,以治愈或延缓创伤性关节炎的发生发展。     

软骨细胞线粒体功能异常对骨关节炎发病机制的研究

骨关节炎(osteoarthritis, OA)主要是关节软骨退变导致的慢性炎症性关节疾病，病因及发病机制复杂，最新研究发现，软骨细胞中的线粒体功能异常与OA发病机制密切相关。线粒体通过调控软骨细胞衰老、凋亡、氧化应激、炎症抑制，参与OA发病进程。此外，线粒体相关信号通路AMPK/SIRT3对于调节软骨细胞的代谢过程很重要，表明这些可能是OA治疗的目标。因此，该文论述软骨细胞线粒体功能异常与OA的发病机制的相关性。     

骨性关节炎关节软骨损伤与修复的研究进展

骨性关节炎曾被认为是一种关节的退行性病变，但近年的研究证实，其病变是由于机械性外伤或炎症等多因素造成关节软骨损伤，而使软骨成分产生自身免疫反应，造成继发性的关节软骨破坏。其机制主要是关节软骨的蛋白多糖合成受到抑制及胶原纤维受到破坏，使软骨丧失其弹性，增加了液压渗透性而使软骨细胞承受的压应力增高，分解酶增加，滑润作用下降而致关节软骨表面破坏。     

骨关节炎的细胞生物学研究进展

骨关节炎的细胞生物学变化主要包括:软骨细胞增殖和凋亡、细胞的合成和降解活动改变、软骨细胞的表型变化和骨赘形成。骨关节炎中软骨细胞的最初变化是重新合成软骨大分子、ⅡA型和Ⅲ型原胶原,分泌活性蛋白水解酶。“去分化”到成纤维细胞样表型在早期并不明显。软骨细胞增生并在近软骨表面处形成“丛”,在钙化软骨中有细胞凋亡。此外,随着年龄的增长,软骨细胞进行性衰老,关节软骨的修复能力下降,使骨关节炎的发病率增高。     

一氧化氮对软骨代谢影响的研究进展

人和动物的炎症关节中一氧化氮（ＮＯ）含量增高,关节中ＮＯ产生主要来源于关节软骨细胞和滑膜细胞。增高的ＮＯ可引起软骨代谢紊乱;抑制软骨细胞增殖,促使软骨细胞凋亡;抑制软骨细胞蛋白多糖（ＰＧ）、胶原合成,促进软骨细胞ＰＧ、胶原分解;促进软骨细胞糖酵解,从而导致关节软骨修复能力降低、软骨破坏增加。ＮＯ对软骨代谢的影响与类风湿性关节炎（ＲＡ）、骨关节病（ＯＡ）的发生、发展关系密切。抑制ｉＮＯＳ的表达、ＮＯ的产生,有可能成为治疗ＲＡ、ＯＡ的新途径     

一氧化氮合成酶在骨关节炎关节软骨及骨刺中的表达

目的与方法：近年来，一氧化氮在骨科领域广泛的生物学作用，引起骨科界普遍重视。本文用组化及免疫组化方法研究骨性关节软骨及骨刺中诱导型一氧化氮合成酶的表达。结果发现：一氧化氮合成酶在极早期软骨损伤中表达，定位于关节软骨表层细胞的胞浆内；在骨性关节炎关节软骨中，全层表达，以软骨细胞团表达明显，在骨刺中，表达丰富，以骨膜中软骨祖细胞层，软骨细胞团（尤其是肥大样改变的软骨细胞）、破骨细胞及成骨细胞表达明显。     

膝骨性关节炎合并骨质疏松症调节机制的研究进展

膝骨性关节炎和骨质疏松症都是与年龄增长相关的骨与关节退行性疾病,两者在发病机制、病理变化、调节机制、临床治疗等方面存在着诸多的共同点,在膝骨关节炎和骨质疏松症的进程中通过复杂的调节机制维持骨代谢平衡、减轻炎症、保护关节软骨、稳定膝关节,进而延缓膝关节的退变;虽然两者间复杂的调节机制已有研究,但是仍然不完善。本研究从炎症、生物力学、激素与骨代谢、遗传、蛋白等方面对膝骨性关节炎并骨质疏松症的调节机制进行了综述,以期为临床防治该病提供新的思路和理论依据。     

Osteoblasts derived from osteophytes produce interleukin-6, interleukin-8, and matrix metalloproteinase-13 in osteoarthritis

To clarify the significance of the osteophytes that appear during the progression of osteoarthritis (OA), we investigated the expression of inflammatory cytokines and proteases in osteoblasts from osteophytes. We also examined the influence of mechanical stress loading on osteoblasts on the expression of inflammatory cytokines and proteases. Osteoblasts were isolated from osteophytes in 19 patients diagnosed with knee OA and from subchondral bone in 4 patients diagnosed with femoral neck fracture. Messenger RNA expression and protein production of inflammatory cytokines and proteases were analyzed using real-time RT-PCR and ELISA, respectively. To examine the effects of mechanical loading, continuous hydrostatic pressure was applied to the osteoblasts. We determined the mRNA expression and protein production of IL-6, IL-8, and MMP-13, which are involved in the progression of OA, were increased in the osteophytes. Additionally, when OA pathological conditions were simulated by applying a nonphysiological mechanical stress load, the gene expression of IL-6 and IL-8 increased. Our results suggested that nonphysiological mechanical stress may induce the expression of biological factors in the osteophytes and is involved in OA progression. By controlling the expression of these genes in the osteophytes, the progression of cartilage degeneration in OA may be reduced, suggesting a new treatment strategy for OA.     

Bone and high-density lipoprotein:The beginning of a beautiful friendship

There is a tight link between bone and lipid metabolic pathways.In this vein,several studies focused on the exploration of high-density lipoprotein(HDL)in the pathobiology of bone diseases,with emphasis to the osteoarthritis(OA)and osteoporosis,the most common bone pathologies.Indeed,epidemiological and in vitro data have connected reduced HDL levels or dysfunctional HDL with cartilage destruction and OA development.Recent studies uncovered functional links between HDL and OA fueling the interesting hypothesis that OA could be a chronic element of the metabolic syndrome.Other studies have linked HDL to bone mineral density.Even though at epidemiological levels the results are conflicting,studies in animals as well as in vitro experiments have shown that HDL facilitates osteoblastogensis and bone synthesis and most probably affects osteoclastogenesis and osteoclast bone resorption.Notably,reduced HDL levels result in increased bone marrow adiposity affecting bone cells function.Unveiling the mechanisms that connect HDL and bone/cartilage homeostasis may contribute to the design of novel therapeutic agents for the improvement of bone and cartilage quality and thus for the treatment of related pathological conditions.     

骨关节炎病因及小鼠模型相关研究进展

骨关节炎是最常见的退行性关节病变,常见于老年人.骨关节炎的特征性改变是关节软骨进行性退变、软骨细胞凋亡、软骨下骨重建、炎症、滑膜炎和骨赘形成,引起受累关节疼痛、活动受限并最终导致关节功能障碍.骨关节炎的病因主要包括年龄、肥胖、关节损伤、炎性因子和遗传因素等.伴随着社会人口老龄化进程的加速,骨关节炎发病率逐年升高,并成为严重的社会医学问题.由于其病因复杂多样,目前没有确切的结论,故缺乏有效的治疗手段.本文对骨性关节炎病因及用于骨关节炎病因研究的小鼠模型进展进行综述,对骨关节炎的病理机制进行阐述,以期为骨关节炎的治疗带来新思路.     

氧化应激调控MAPK信号通路与骨关节炎治疗研究进展

骨关节炎(osteoarthritis, OA)是一种常见的中老年慢性疾病，其发病原因与多因素相关，病理表现为软骨、软骨下骨的破坏以及滑膜炎症，以关节疼痛为主要症状。尽管OA的诊疗已逐步完善，但其病理生理机制尚未完全清楚。氧化应激状态下活性氧类(ROS)对软骨内环境稳态有着重要影响，与OA的发生发展有着密切关系。促分裂原活化的蛋白激酶(MAPK)信号通路是介导OA病情进展的最重要的信号通路，该信号通路过表达可以激活多种炎性因子，促进软骨细胞与基质降解，加速OA的发生发展。研究表明MAPK信号通路对OA的调控作用受到ROS水平的影响。因此，通过抑制机体氧化应激降低MAPK信号通路相关因子的表达可以起到治疗OA的作用，为OA的治疗提供新方向和研究思路。     

Emerging role of metabolic signaling in synovial joint remodeling and osteoarthritis

Obesity and associated metabolic diseases collectively referred to as the metabolic syndrome increase the risk of skeletal and synovial joint diseases, including osteoarthritis (OA). The relationship between obesity and musculoskeletal diseases is complex, involving biomechanical, dietary, genetic, inflammatory, and metabolic factors. Recent findings illustrate how changes in cellular metabolism and metabolic signaling pathways alter skeletal development, remodeling, and homeostasis, especially in response to biomechanical and inflammatory stressors. Consequently, a better understanding of the energy metabolism of diarthrodial joint cells and tissues, including bone, cartilage, and synovium, may lead to new strategies to treat or prevent synovial joint diseases such as OA. This rationale was the basis of a workshop presented at the 2016 Annual ORS Meeting in Orlando, FL on the emerging role of metabolic signaling in synovial joint remodeling and OA. The topics we covered included (i) the relationship between metabolic syndrome and OA in clinical and pre‐clinical studies; (ii) the effect of biomechanical loading on chondrocyte metabolism; (iii) the effect of Wnt signaling on osteoblast carbohydrate and amino acid metabolism with respect to bone anabolism; and (iv) the role of AMP‐activated protein kinase in chondrocyte energetic and biomechanical stress responses in the context of cartilage injury, aging, and OA. Although challenges exist for measuring in vivo changes in synovial joint tissue metabolism, the findings presented herein provide multiple lines of evidence to support a central role for disrupted cellular energy metabolism in the pathogenesis of OA. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:2048–2058, 2016.     

骨关节炎的诊治与研究进展

骨关节炎(osteoarthritis,OA)是影响人类健康最常见的关节疾患之一,人群发病率约为2%～6%,是导致50岁以上人群功能残疾、造成经济损失和影响社会发展的主要疾病之一.骨关节炎具有临床、病理和影像学多重定义;在其疾病发生与发展过程中,在全身因素和局部因素综合作用下,关节软骨发生生化、结构和代谢改变,最终出现关节软骨软化、破溃和局部剥脱以及关节边缘骨与软骨赘生物形成等病理改变,并引起相应临床症状;骨关节炎相关的滑膜炎症是软骨基质降解产物引起的继发性改变,滑膜炎性病变在骨关节炎的发生中不是旁观者,而是关节结构破坏的参与者,促进了骨关节炎的病程进展.骨关节炎的治疗目标是控制疼痛、改善关节功能和生活质量,尽可能避免治疗的毒副作用.目前,骨关节炎缺乏治愈的手段.但是,针对患者设计的个体化治疗方案可以减轻疼痛、保持或改善关节活动度,减缓关节功能的受损.应重视对患者的教育和康复治疗,特异性COX-Ⅱ抑制剂减少了胃肠道副反应事件的发生.当内科保守治疗无效,而日常活动进行性受限时,应该考虑关节镜清理、截骨术和关节置换手术等外科治疗.软骨移植、氨基葡萄糖、针对炎性因子或细胞内与炎症相关的信号分子的生物治疗手段为骨关节炎的治疗开辟了新的研究方向.     

Estrogen and osteoarthritis

In menopausal women and the elderly, populations most often affected by osteoarthritis (OA), estrogen levels are lower than normal, which suggests that estrogen may be an important regulator of OA. Estrogen can influence chondrocyte function on multiple levels by interacting with cellular growth factors, adhesion molecules, and cytokines. Nevertheless, findings regarding a correlation between estrogen and OA are inconsistent and inconclusive and range from estrogen protecting against OA to cartilage damage mediated by high levels of estrogen and higher binding to estrogen receptors. In this review, we summarize current in vivo and in vitro research and discuss future directions for analyses of the role of estrogen in OA.     

细胞因子在骨关节炎软骨退变中的作用

骨关节炎(Osteoarthritis,OA)是一种以关节软骨破坏,软骨下骨和滑膜反应为特征的慢性进行性骨关节疾病。近年报道细胞因子作为调节者,通过各种机制调节软骨细胞的功能活动,在关节软骨退变中起到了重要的作用,本文就相关因子作一综述。     

Arthrosen bei hereditären Stoffwechselerkrankungen

Primary osteoarthritis (OA) of peripheral joints is a common disease mainly occurring after the age of 50. It is important to distinguish primary from secondary OA. Younger age at disease onset, rapid progression, unusual disease manifestations and co-morbidities are signs of secondary OA. This review outlines an important group of secondary OA. Hereditary metabolic diseases can exhibit joint involvement. For some of these diseases, correct diagnosis is critical, since appropriate therapy influences not only joint function and quality of life, but can also prevent relevant end-organ damage.     

骨关节炎与骨质疏松症的相关性研究分析

骨质疏松症(osteoporosis,OP)及骨关节炎(osteoarthritis,OA)是两种常见的老年性疾病,随着我国人口老龄化程度的不断加剧,它们已成为影响老年人生活质量的两大主要骨与关节疾患.为了进一步阐述两者的相互关系,笔者以国内外骨关节炎和骨质疏松症相关性的最新研究为基础,总结了两者之间的可能联系.笔者发...