骨髓间充质干细胞来源外泌体及其相关信号通路在激素性股骨头坏死中作用的研究进展*

骨髓间充质干细胞是具有多向分化能力的一种干细胞,近年来有关研究发现骨髓间充质干细胞分泌的外泌体具有促进损伤肌腱修复、血管生成、抑制氧化应激反应、保护神经细胞、促进软骨再生、调节骨代谢等功能。而激素性股骨头坏死是由于大量使用激素导致的股骨头无菌性坏死,其具体作用机制尚未阐明,相关信号通路,如Wnt/β-catenin、RANKL-RANK、PTEN/AKT、PI3K/AKT等通路在其中起着关键的作用,而这些信号通路的激活又与外泌体密切相关,综述了骨髓间充质干细胞来源外泌体及其相关信号通路在激素性股骨头坏死中作用的有关研究进展,以期对激素性股骨头坏死的防治及相关药物研发有一定指导意义。     

线粒体相关蛋白与股骨头坏死关联性研究进展

骨组织细胞凋亡和自噬学说越来越被认同,逐渐成为人们研究股骨头坏死发病机制的焦点.在刺激因素作用后,线粒体功能障碍,影响自噬,诱发骨组织细胞凋亡,最终导致股骨头坏死的发生和发展.这一关联的发现对进一步阐明本病的发病机制具有重要意义,同时检测线粒体相关蛋白可能对股骨头坏死早期诊断和预后判断有较高的参考价值,也为未来调控相关...     

激素性股骨头坏死患者骨髓间充质干细胞体外增殖分化能力的研究

通过对激素性股骨头坏死患者股骨头部骨髓间充质干细胞(bone marrow mesenchymal stem cells,BMSCs)增殖及成骨、成脂分化能力的研究,探讨激素性股骨头坏死的发病机理及自体BMSCs移植治疗股骨头坏死的可行性。选择激素性股骨头坏死患者10例,无股骨头坏死的股骨颈骨折患者10例作为对照组。两组患者在行全髋关节置换术中抽取股骨头部骨髓血,密度梯度离心法分离BMSCs并培养至第3代细胞,流式细胞仪检测细胞特异性表面抗原,成纤维细胞–集落形成实验以及成骨、成脂诱导培养后分析细胞的增殖及成骨、成脂分化能力。结果显示,股骨头坏死组细胞表达BMSCs特异性表面抗原CD44、CD73;股骨头坏死组BMSCs形成集落数明显低于对照组;股骨头坏死组碱性磷酸酶活性和钙结节数均低于对照组;股骨头坏死组的成脂细胞数明显高于对照组。该研究结果表明,激素性股骨头坏死患者股骨头BMSCs的增殖及成骨分化能力下降,但其成脂分化潜能增强,推测BMSCs增殖及分化能力的改变可能参与激素性股骨头坏死病理生理过程。     

淫羊藿方治疗早中期激素性股骨头坏死的临床观察

目的:评定淫羊藿方对早、中期激素型股骨头坏死的治疗效果。方法:将60例早、中期激素型股骨头坏死患者随机分为治疗组、对照组。治疗组服用淫羊藿方,对照组服用仙灵骨葆胶囊。两组评定临床效果并对比。结果:淫羊藿方显效率明显优于仙灵骨葆胶囊。结论:淫羊藿方治疗早、中期激素型股骨头坏死疗效确切。     

间断应用激素法制备兔股骨头缺血性坏死模型

目的 通过比较持续应用激素组与间断应用激素组实验动物在死亡率、x线片、ECT、MRI和光镜下表现,制备激素性股骨头缺血性坏死模型,探讨降低实验动物死亡率的方法.方法 40只新西兰大耳白兔分2组.对照组20只,臀肌注射醋酸氧化泼尼松龙,按8 mg/kg,每周两次,共8周16次;实验组20只,臀肌注射醋酸氢化泼尼松龙,按8 mg/kg,注射3周,停药3周,再继续用药5周.分别于注射药物后2、4、6、8周处死,取材前分别做X线片、ECT、MRI检查,取材后光镜观察骨髓、骨细胞、骨小梁的变化.结果 死亡率比较,实验组明显低于对照组(PO.05).讨论 ①大剂量激素对实验动物的打击是相当严重的,对于机体免疫系统和循环系统的损害是其死亡的主要原因.②持续应用激素组与间断应用激素组均制造出成功的股骨头坏死模型,间隔停药期骨组织坏死程度不仅没减轻而是进一步加重.     

成骨细胞移植和成骨生长肽对股骨头坏死修复作用的实验研究

目的：研究成骨细胞移植和成骨生长肽（OGP）对激素性股骨头坏死的影响。方法：25只健康成年日本大耳白兔,随机分为正常组（5只）,实验组（10只）和对照组（10只）。实验组和对照组注射醋酸泼尼松龙致使激素性股骨头坏死后,前者成骨细胞移植于动物股骨头并且OGP注射4、8周,后者注射等量生理盐水。测定血清碱性磷酸酶（ALP）、骨钙素（BGP）,测试股骨头力学性质,通过光镜和扫描电镜观察股骨头的形态结构。结果：实验组血清ALP、BGP明显高于对照组（P〈0．05）。实验组股骨头的最大压缩载荷及载荷／位移较对照组高（P〉0.05）。光镜、扫描电镜观察到实验组股骨头中骨小梁形态及胶原纤维排列有序性明显好于对照组。结论：成骨细胞移植和OGP注射对股骨头坏死具有一定的修复作用。     

重组人骨保护素对激素性股骨头坏死患者骨密度及髋关节Harris评分 的影响

目的:探讨重组人骨保护素对于激素性股骨头坏死患者的骨密度和髋关节Harris评分的影响。方法:选取我院骨科已经确诊的110例激素性股骨头坏死患者,随机分为对照组(给予仙灵骨葆胶囊)和观察组(给予仙灵骨葆胶囊和重组人骨保护素),连续治疗4周,检测并比较两组患者治疗前后的骨密度、髋关节Harris评分、血清抗酒石酸酸性磷酸酶(TRAP)、Ⅱ型胶原羧基端端肽(CTX-Ⅱ)水平以及复发率变化。结果:与对照组相比较,观察组患者腰椎骨和股骨近端的骨密度较高平(P0.05);髋关节Harris评分总有效率(92.73%)显著高于对照组(76.36%)(P0.05)。两组血清TRAP及CTX-Ⅱ水平显著低于治疗前,且试验组血清TRAP及CTX-Ⅱ水平显著低于对照组(P0.05),与对照组相比,观察组复发率较低(P0.05)。结论:重组人骨保护素能够抑制骨吸收,提高骨密度和强度,改善髋关节功能,有望成为激素性股骨头坏死的新型治疗方法。     

激素诱导血清病动物骨坏死模型中的脂类代谢异常

目的初步探讨血清病动物激素性骨坏死的发病机制。方法将新西兰大白兔分为三组,A组联合应用马血清和地塞米松磷酸钠诱导骨坏死模型,B组单纯应用地塞米松磷酸钠,C组应用生理盐水作为对照组,对三组实验兔股骨头进行HE、MRI观察,并对各组兔的血脂、AST和ALT进行检测,分析比较。结果A组出现了典型的股骨头缺血坏死改变,血脂、AST和ALT与另外两组相比差异有显著性。单纯应用激素组和对照组未出现股骨头缺血坏死。结论运用马血清和地塞米松磷酸钠可成功诱导出兔骨坏死模型,血管炎、血脂代谢异常和肝功能损害共同导致股骨头缺血坏死发生,短期应用大剂量激素难以诱导出骨坏死模型。     

骨保护素对激素性股骨头坏死患者功能恢复及血清TRAP和CTX-Ⅱ水平的影响

目的:探讨骨保护素对激素性股骨头坏死患者功能恢复及血清抗酒石酸酸性磷酸酶(TRAP)和Ⅱ型胶原羧基端端肽(CTX-Ⅱ)水平的影响。方法:选取2014年1月~2016年6月我院骨科收治的130例激素性股骨头坏死患者作为研究对象,采取随机数字表将其分成两组,每组65例。两组患者均给平卧床、患肢持续皮牵引治疗,观察组在此基础上联合使用骨保护素治疗,比较两组临床疗效、功能恢复情况以及治疗前后骨密度、血清TRAP与CTX-Ⅱ水平。结果:观察组治疗优良率为90.77%,相对于对照组的72.31%明显上升(P0.01)。两组治疗后股骨头局部骨密度均有上升(P0.01),其中观察组上升更为明显(P0.01);观察组治疗后腰椎平均骨密度与治疗前相比有明显上升(P0.01),对照组无明显变化(P0.05)。两组治疗后血清TRAP与CTX-Ⅱ水平均较治疗前显著下降(P0.01),但观察组下降更为明显(P0.01)。结论:骨保护素治疗激素性股骨头坏死可有效抑制骨吸收、增强骨密度、改善患髋关节功能。     

早期激素性股骨头坏死模型的建立

目的:建立早期股骨头坏死模型,为研究其发病机制及合理治疗方法的提供可靠的模型基础。方法:用单一剂量脂多糖LPS(10μg/kg)联合三次甲强龙MPS(10 mg/kg)注射,每次间隔24h,诱导建立兔早期股骨头坏死模型,通过影像学及组织病理性学方法评估模型建立情况。结果:4周后,模型组死亡1例,模型组16例X线检查未见异常表现,2例X线提示股骨头密度不均,未出现股骨头塌陷,18例HE染色示骨细胞空骨陷窝增多,脂肪细胞体积变大,数量增多。结论:用脂多糖(LPS)联合甲强龙可成功诱导建立兔早期股骨头坏死模型,模型成功率高、死亡率低。     

非创伤性股骨头坏死的机制及早期治疗的研究进展

非创伤性股骨头坏死(NONFH)是临床常见的骨科难治性疾病之一,本文就其发病机制和临床治疗研究的相关进展和问题展开综述,旨在进一步提高对NONFH的临床认识和治疗水平。股骨头坏死的机制仍然没有统一的定论,但各种机制最终归于股骨头供血区域血液瘀滞,导致股骨头发生缺血坏死虽然目前还没有一种治疗方法达到理想的治疗效果,髓心减压仍然是应用最为广泛的早期治疗手段,各种改进手术如骨移植、钽棒移植、骨髓干细胞移植和生长因子移植是今后的主要趋势。     

A new animal model of femoral head necrosis induced by intraosseous injection of ethanol

There is no reliable animal model of the early stages of osteonecrosis of the femoral head (ONFH) for the evaluation of new therapeutic approaches. In this study, we propose a new animal model of femoral head osteonecrosis. Pure ethanol was injected into the centre of the femoral head in adult Merino sheep under fluoroscopic control. After 3, 6 and 12 weeks the animals were killed and the femoral heads were harvested. Microradiographic and histological changes were analysed and recorded. Partial necrosis was documented over a period of 12 weeks in all animals. The appearance of necrosis in combination with intact macrotexture, macrocirculation and joint cartilage is similar to the features described in early ONFH in humans. Due to its efficacy and its similarity to the early stages of ONFH in humans, this model may be suitable to evaluate new therapeutic techniques in the treatment of ONFH.     

Icariin promotes angiogenesis in glucocorticoid‐induced osteonecrosis of femoral heads: In vitro and in vivo studies

The injury and dysfunction of the femoral head microvascular endothelial cells are associated with the pathogenesis of glucocorticoid‐induced osteonecrosis of the femoral head (ONFH). Reports indicate that icariin (ICA) can enhance vascular roles and also inhibit endothelial cell dysfunction. However, it still remains unclear whether ICA can promote angiogenesis in glucocorticoid‐induced ONFH. In this study, we investigate this hypothesis through in vitro and in vivo experiments. Results showed that 0.1 mg/mL hydrocortisone significantly suppressed bone microvascular endothelial cells (BMECs) proliferation while ICA at 10^?5 mol/L reversed this inhibition. ICA significantly promoted BMECs migration, tube formation, the angiogenesis‐related cytokines expression and the activation of Akt. Furthermore, ICA enhanced Bcl‐2 expression but diminished Bax expression. According to in vivo results, rats with ICA treatment exhibited a lower ratio of empty lacunae, higher volume of blood vessels and more CD31‐positive cells. This study revealed that ICA promotes angiogenesis of BMECs in vitro and improves femoral head blood vessel volume of rats treated with glucocorticoid, suggesting the efficacy of ICA in the prevention of glucocorticoid‐induced ONFH.     

Aspects des complications ostéo-articulaires de la maladie de Gaucher de type 1 en scintigraphie osseuse planaire (infection exclue) : à propos d’un cas

Type 1 Gaucher disease is an autosomal recessive inheritance lysosome storage disorder, corresponding to an inherited deficiency of glucocerebrosidase. Bone complications are frequently revealing and constitute the main source of morbidity and disability. They can appear on the acute (osseous infarction, acute osteomyelitis) or chronic mode (bone modelling disorders, osteopenia, osteonecrosis, chronic osteomyelitis). The aim of our work is to evaluate the contribution of the 99mTc labeled diphosphonates bone scan in the case of a 28-year-old patient, followed up for type 1 Gaucher disease and presenting for 2 months knees and pelvis inflammatory pain with functional impotence. X-ray had shown a stage IV aseptic osteonecrosis of the right femoral head. The bone scan found other osteo-articular lesions of the left hip, knees and right tibia related to Gaucher disease with a high likelihood. Bone scan is a very sensitive procedure in the early diagnosis and in the follow-up of bone complications of type 1 Gaucher disease. Bone scan allows to clinically silent lesions on the whole skeleton.     

Corticosteroid reduces blood flow to femoral heads in rabbits

Avascular necrosis of the femoral head is one of the common problems in orthopedic practice in Taiwan. The subchondral bone loses its blood supply which weakens its biomechanical support. Steroid overuse is one of many possible etiologies in reducing blood flow to the femoral head. Laser Doppler velocimeter is a precise monitor of regional blood flow of bone which is expressed in perfusion units (PU). In the control group the rabbits were injected with normal saline and there were no statistical differences between blood flow to the right hip (39.26±5.64 PU) and left hip (38.58±4.35 PU). In group B a weekly injection of methylprednisolone into rabbits for 6 weeks demonstrated the reduction of blood flow of femoral head (24.74±3.13 PU) by the laser Doppler velocimeter. The flow decreased further (15.93±2.33 PU) by 12 weeks of steroid treatment. In group C after a weekly injection of steroid for 6 weeks the flow became 31.63±4.79 PU. The steroid was then discontinued for 3 weeks and the flow was 34.6±1.34 PU. In group D the blood flow was 25.89±4.01 PU after 6 weeks of steroid treatment and we stopped the steroid for 6 weeks, the blood flow became 29.86±2.59 PU. The merit of our experiment established a model of study in avascular necrosis of the femoral head in rabbits.     

Osteocyte-based image analysis for quantitation of histologically apparent femoral head osteonecrosis: application to an emu model

Femoral head osteonecrosis is often characterized histologically by the presence of empty lacunae in the affected bony regions. The shape, size and location of a necrotic lesion influences prognosis, and can, in principle, be quantified by mapping the distribution of empty lacunae within a femoral head. An algorithm is here described that automatically identifies the locations of osteocyte-filled vs. empty lacunae. The algorithm is applied to necrotic lesions surgically induced in the emu, a large bipedal animal model in which osteonecrosis progresses to collapse, as occurs in humans. The animals' femoral heads were harvested at sacrifice, and hematoxylin and eosin-stained histological preparations of the coronal midsections were digitized and image-analyzed. The algorithm's performance in detecting empty lacunae was validated by comparing its results to corresponding assessments by six trained histologists. The percentage of osteocyte-filled lacunae identified by the algorithm vs. by the human readers was statistically indistinguishable.