破骨细胞形成和骨吸收机理

破骨细胞形成和骨吸收机理赵守亮综述史俊南肖明振审阅西安第四军医大学口腔医学院（７１００３２）破骨细胞是具有破坏骨组织和其它矿化物能力的一群多核细胞，它不仅在病理条件下，而且在生理条件下也起着重要的作用，如：骨组织的发育、功能性改建等，都是在破骨细胞与...     

破骨细胞整合素的功能

整合素是一类重要的细胞表面跨膜蛋白，介导细胞粘附，并参与细胞内外的信号传递。近年来研究发现，它在破骨细胞迁移、分化、粘附、信号传导等过程中起重要作用，本文对其研究现状作一综述。     

破骨细胞整合素的功能

整合素是一类重要的细胞表面跨膜蛋白,介导细胞粘附,并参与细胞内外的信号传递。近年来研究发现,它在破骨细胞迁移、分化、粘附、信号传导等过程中起到重要作用,本文对其研究现状作一综述。     

破骨细胞与颌骨骨吸收研究展望

颌骨在全身骨组织中占有重要而特殊的地位，其包绕牙齿的部分——牙槽骨，由于与牙齿的密切关系，是全身骨代谢最活跃的部分。多种疾患，如颌骨的炎症、囊肿、肿瘤、骨质疏松症等均可引起颌骨与牙槽骨骨质吸收亢进，致使牙齿松动、脱落，影响咀嚼功能，甚至引起颌骨局部缺损，影响颌面部     

钛颗粒对破骨细胞骨吸收功能影响的研究

目的:研究钛颗粒对破骨细胞骨吸收功能的影响。方法:分别将含有和不含有钛颗粒的培养基与诱导的破骨细胞联合培养48h后,检测破骨细胞的骨吸收陷窝,破骨细胞对钛颗粒的吞噬及钛颗粒对破骨细胞骨架的影响。结果:钛颗粒培养基组份的骨吸收陷窝面积明显大于比不含钛颗粒培养基的组份,钛颗粒可被破骨细胞吞噬,但对其细胞骨架无显著影响。结论:钛颗粒可促进破骨细胞的骨吸收功能。     

破骨细胞前体细胞的研究进展

破骨细胞前体细胞由骨髓中的造血干细胞生成,许多细胞因子或生长因子可直接或间接地诱导破骨细胞前体细胞形成破骨细胞介导骨吸收.在多种常见骨病中,阻断前体细胞分化为破骨细胞的信号通路可能是一种有效防止骨吸收的治疗策略.本文就破骨细胞前体细胞的来源与特点、破骨细胞前体细胞的功能调控等研究进展作一综述.     

骨形成蛋白对破骨细胞的调节作用

骨形成蛋白与骨、软骨、肌腱、牙周组织、牙本质的形成有极为密切的关系,具有明确的诱导骨形成作用。但是,国外学者研究发现,骨形成蛋白对破骨细胞也具有正向作用,可以促进骨髓基质细胞和脾细胞等分化成为多核的破骨样细胞。本文就骨形成蛋白对破骨细胞调节作用的研究进展作一综述。     

大黄对破骨细胞性骨吸收作用的研究

从出生２４小时内的日本大耳白兔的四肢长骨中分离出破骨细胞，与牛骨磨片共同培养，培养液中加入大黄素，使终浓度为５×１０６ｍｏｌ／Ｌ和ｌ０５ｍｏｌ／Ｌ，另做空白对照。利用相差显微镜动态观察破骨细胞吸收骨的情况，连续观察７天。计数每个骨片上所形成的吸收陷窝数，并做统计学分析。结果表明：１０５ｍｏｌ／Ｌ的大黄可抑制破骨细胞性骨吸收，使破骨细胞在骨片上形成的吸收陷窝数减少（Ｐ＜０．０５）；而５×ｌ１０－６ｍｏｌ／Ｌ的大黄素虽可部分抑制破骨细胞性骨吸收，但对破骨细胞在骨片上形成的吸收陷窝数无明显影响（０．０５＜Ｐ＜０．２）。     

主穹隆蛋白通过抑制破骨细胞分化在牙周炎中起骨保护作用

目的:通过建立小鼠实验性牙周炎模型及体外骨髓间充质干细胞(BMMSCs)破骨细胞向诱导,探讨主穹隆蛋白(MVP)在牙周炎骨吸收中的作用。方法:MVP基因敲除(MVP-/-)和野生型(WT)C57BL/6小鼠分别局部注射脂多糖(LPS)以建立实验性牙周炎模型,通过micro CT扫描、耐酒石酸酸性磷酸酶(TRAP)染色等方法检测骨吸收程度。同时,体外分离培养MVP-/-与WT C57BL/6小鼠的BMMSCs,并诱导其向破骨细胞分化,通过TRAP染色、麦胚凝集素(WGA)染色等方法观察MVP对BMMSCs破骨向分化及骨吸收活性的影响。结果:在LPS诱导的小鼠实验性牙周炎中,MVP-/-组小鼠牙周炎骨吸收更为明显,且在注射区域内可见更多破骨细胞;体外实验证明,MVP-/-组小鼠的BMMSCs分化形成更多的破骨细胞,且骨吸收更明显。结论:MVP可以抑制破骨细胞分化,在牙周炎中起骨保护作用。     

Grafting of deproteinized bone particles inhibits bone resorption after maxillary sinus floor elevation

OBJECTIVES: To evaluate the value of deproteinized bone particles on bone resorption in the augmented space after maxillary sinus floor elevation in rabbits. MATERIAL AND METHODS: A total of 20 rabbits underwent bilateral grafting, using blood clots (control group) and deproteinized bone particles (experimental group), and followed with histologic and histomorphometric analysis. RESULTS: Two weeks after grafting, the augmented space was almost completely obliterated by both newly formed bone and fibrous connective tissue in the control group. Some osteoclasts were found on the surface of newly formed bone, especially near the elevated sinus membrane. In the experimental group, newly formed bone was found along the elevated sinus membrane, the cortical wall of the augmented space, and the surface of deproteinized bone particles near the cortical wall. Some osteoclasts were found along the deproteinized bone particles and a few adhered to the surface of the newly formed bone. Eight to 10 weeks after implantation in the control group, most of the newly formed bone had been resorbed. In the experimental group, newly formed bone was found in most parts of the convex augmented space. Histomorphometrical analysis showed that the augmented height was significantly higher in the experimental group than in the control group at all evaluation times. Bone area was significantly higher in the experimental group than in the control group at 6, 8, and 10 weeks after implantation. The area of grafted deproteinized bone particles did not change significantly from 2 to 10 weeks. CONCLUSION: Slowly resorbed deproteinized bone particles contribute to stable augmentation of the maxillary sinus floor by inhibiting bone resorption.     

The gingipains from Porphyromonas gingivalis do not directly induce osteoclast differentiation in primary mouse bone marrow cultures

Background and Objective:  Porphyromonas gingivalis is a major aetiological agent in the development of periodontitis, the major clinical hallmark of which is bone resorption. The cysteine proteases (gingipains) produced by P. gingivalis have a critical role in the pathogenesis of the disease, and previous studies on whole bacteria have implicated these enzymes in osteoclastogenesis, a process which serves to upregulate bone resorption. The effects of the gingipains from P. gingivalis on osteoclast differentiation were investigated here to determine whether the enzymes directly contribute to osteoclastogenesis and thus to bone resorption.
Material and Methods:  The effects of the gingipains on osteoclast differentiation were investigated in primary mouse bone marrow cultures. The cultures harvested from C57BL6/J mice were incubated in the presence of parathyroid hormone, a known osteoclastogenic factor, or active/inactivated forms of three gingipains. Osteoclast differentiation was quantified by counting the number of multinucleated cells positive for tartrate-resistant acid phosphatase, an enzyme marker for these cells.
Results:  After 10 days of culture, the gingipains, either active or inactive, failed to stimulate osteoclast differentiation in comparison to the parathyroid hormone.
Conclusion:  The data presented here demonstrate that the gingipains do not induce osteoclast differentiation in this system, indicating that the bacterium uses other mechanisms to induce bone loss.     

微小RNAs在破骨细胞分化调控中的研究进展

微小RNAs（miRNAs）是一组由22~25个核苷酸构成的非编码单链RNA,具有基因转录后调控功能,广泛参与细胞增殖、分化、凋亡、组织炎症及肿瘤发生等过程。破骨细胞是体内唯一具有骨吸收功能的细胞,受成骨细胞及炎症因子的调控,在牙周炎骨吸收过程中具有重要作用。miRNAs对破骨细胞的分化、成熟及功能具有多重调控作用。本文就miRNAs调控破骨细胞分化和功能的可能机制,及其在牙周炎骨吸收过程中的作用进行综述。     

Human osteoclast formation and activity on an equine spongy bone substitute

Objectives: The aim of the present study was to evaluate the in vitro formation and activity of human osteoclasts (OCLs) generated on a new type of xenograft for bone substitution, an equine spongy bone.
Material and methods: Peripheral blood mononuclear cells from healthy volunteers were used to generate OCLs in vitro in the presence of macrophage colony stimulating factor (M-CSF) and receptor activator of NF-κB ligand (RANKL) on bovine bone slices (positive control) and equine spongy bone. Morphological and biochemical methods were used to assess OCLs formation and activity.
Results: Cells generated after 21 days of culture on equine spongy bone showed similar morphology to those on the positive control and displayed typical OCL markers and features, indicating that this material supported OCL formation. Moreover, these cells were functionally active on equine spongy bone with statistically significant differences compared with the control in the release of tartrate-resistant acid phosphatase (TRAcP5b) at days 14 and 21 of culture. With regard to the resorption, on equine bone, OCLs formed smaller discontinuous island-like lacunae rather than the typical lobulated, tracking resorption lacunae observed on the control.
Conclusions: This study enables clinicians to tailor the usage of equine spongy bone and presents a model, which can be applied to the preclinical assessment of bone substitute material's resorbability and resorption rates.     

破骨细胞分化在颞下颌关节骨关节炎发生中的作用

目的 探究破骨细胞分化在颞下颌关节骨关节炎(TMJOA)发生中的作用.方法 构建小鼠TMJOA模型,Micro-CT观察TMJOA发生发展过程中髁突骨质变化,苏木素伊红(HE)染色观察TMJOA关节组织学结构变化,抗酒石酸酸性磷酸酶(TRAP)组织染色观察TMJOA关节组织中破骨细胞的存在情况.收集TMJOA患者滑液,...     

周期性牵张力对骨髓破骨细胞形成的影响

目的 :通过大鼠骨髓破骨细胞的体外诱导培养 ,观察不同时段周期性牵张力对骨髓破骨细胞形成的影响。方法 :通过体外细胞培养加载系统 ,选择频率为 6周 /min ,弹性基底膜发生 12 %形变率的周期性牵张力。试验共分为 4组 ,A组 :为对照组 ,在整个培养期间不加力 ;B组 :从培养的第 2d开始加力 ,连续加力 3d ;C组 :从培养的第 2d开始加力 ,连续加力 5d ;D组 :从培养的第 5d开始加力 ,连续加力 2d。每组各 6孔 ,均于培养的第 7d进行多核细胞计数。结果 :B组、C组多核细胞数量与对照组相比明显减少 (P <0 .0 5 ) ,而D组多核细胞数量与对照组相比无显著性差异 (P >0 .0 5 )。B组与C组相比亦无显著性差异。结论 :周期性牵张力主要是在骨髓诱导培养的早期抑制破骨细胞的形成 ,后期施力对破骨细胞的形成无明显影响。     

低氧条件下HIF调控破骨细胞分化的分子机制研究进展

本文通过低氧引发破骨前体细胞内部信号通路网络,表明骨吸收的部位的局部低氧环境可增强破骨细胞活性,提高其骨吸收功能.目前,低氧促进破骨细胞分化与功能的分子机制尚不明确,因此,为深入研究低氧引发破骨前体细胞内部信号通路网络,探讨低氧诱导因子促进破骨细胞分化及骨吸收的分子机制.     

Notch1蛋白高表达抑制破骨细胞增殖和分化

目的探究体外培养条件下Notch1蛋白高表达对细胞核因子κB受体活化因子配体（RANKL）和巨噬细胞集落刺激因子（MCSF）诱导的骨髓源破骨细胞增殖分化的影响。方法体外培养Rosa-notch1转基因小鼠骨髓间充质干细胞（BMSCs）,采用RANKL和MCSF刺激BMSCs向破骨细胞方向分化。培养至第3天,实验组和对照组分别转染携带Cre重组酶和绿色荧光蛋白（GFP）的重组腺病毒（Ad-Cre-GFP）和携带GFP的重组腺病毒（Ad-GFP）,启动实验组Notch1高表达,采用实时聚合酶链反应（RT-PCR）检测Notch信号通路成分（Notch1、Notch2、Notch3、Notch4、Delta1、Delta3、Delta4、Jagged1）、靶基因（Hes1）mRNA表达量以及抗酒石酸酸性磷酸酶（TRAP）在诱导后mRNA的表达量。采用TRAP染色法观察破骨细胞增殖分化情况。结果TRAP染色显示实验组破骨细胞形成数量明显少于对照组（P<0.05）。与对照组相比,实验组Notch1、Notch3、Jagged1、Delta3、Hes1 mRNA表达量明显增高（P<0.05）,TRAP的mRNA表达量明显降低（P<0.05）。结论Notch1高表达抑制RANKL和MCSF诱导的破骨细胞增殖分化。     

Th1/Th17/Th22 immune response and their association with joint pain,imagenological bone loss,RANKL expression and osteoclast activity in temporomandibular joint osteoarthritis: A preliminary report

It is well accepted that the presence of cytokines belonging to the Th1/Th17/Th22 axis of immuno‐inflammatory response in the joint environment, such as IL‐1β, IL‐17 and IL‐22, respectively, are associated with pathogenesis of several synovial joint degenerative disorders. During temporomandibular joint osteoarthritis (TMJ‐OA), IL‐1β and IL‐17 have been implicated in the inflammation and resorption of sub‐chondral bone; however, the role of Th22 response in the TMJ‐OA pathophysiology has not been established. This study aimed to compare the expression of Th1/Th17/Th22‐type cytokines, chemokines and chemokine receptors in synovial fluid samples obtained from TMJ‐OA or disk displacement with reduction (DDWR) patients. In addition, it aimed to associate these levels with joint pain, imagenological signs of bone degeneration, RANKL production, osteoclastogenesis and osteoclast‐induced bone resorption. Higher levels of IL‐1β, IL‐17 and IL‐22 were expressed in TMJ‐OA compared with DDWR subjects, and these increased levels significantly correlated with RANKL expression, joint pain and articular bone degeneration. Higher levels of CCR5, CCR6 and CCR7, as well as their respective ligands CCL5 and CCL20, responsible for recruitment of IL‐1β, IL‐17 and IL‐22‐producing cells, were over‐expressed in TMJ‐OA compared with DDWR subjects. Osteoclastogenesis and osteoclast‐induced bone resorption were significantly greater in presence of synovial fluid from TMJ‐OA compared with DDWR subjects. These data demonstrate that cytokines, CCLs and CCRs associated with the Th1/Th17/Th22 axis of immuno‐inflammatory response are involved in TMJ‐OA pathogenesis. These findings suggest that IL‐22 is involved in the RANKL expression in TMJ‐OA, which in turn induces differentiation of osteoclasts and subsequent resorption of sub‐chondral bone.