GM-CSF和其诱导的破骨细胞对成骨细胞的影响

目的：探讨GM-CSF和其诱导的破骨细胞对成骨细胞生长的影响。方法：采用分组对照、细胞计数等方法进行研究。结果：GM-CSF和其诱导的破骨细胞可以促进成骨细胞生长。结论：GM-CSF和其诱导的破骨细胞促进成骨细胞增殖、分化，可能是通过破骨细胞内GM-CSF介导的信号通路而发挥作用。     

巨噬细胞集落刺激因子调节破骨细胞活性的研究进展

巨噬细胞集落刺激因子(M-CSF)是一种具有谱系特异性的细胞因子,其受体c-Fims是原癌基因c-fins的表达产物,是一种受体酪氨酸激酶,近年来对M-CSF及其受体c-Fims表达调控以及破骨细胞形成和功能的研究日益增多,在M-CSF与骨代谢疾病关系等方面取得了进展.     

脉冲电磁场对破骨细胞和成骨细胞前体细胞作用的研究

目的 研究脉冲电磁场（PEMFs）对破骨细胞和成骨细胞前体细胞的作用。方法单独离体PEMFs作用：取8周龄雌性SD大鼠股骨骨髓细胞,根据PEMFs作用方式分为4个剂量组和对照组．分别进行成纤维细胞集落形成单位（CFU—F）和粒／巨噬细胞集落形成单位（CFU—GM）培养观察。活体结合离体PEMFs作用：取8周龄雌性SD大鼠随机分为3组：2—70组、OVX组和SHAM组,其中2．70组．OVX组进行双侧卵巢切除手术,SHAM组不切除卵巢。术后12周对2—70组大鼠进行PEMFs作用,OVX组和SHAM组不进行PEMFs作用。作用结束后,取大鼠股骨骨髓。根据体外培养过程中是否继续接受PEMFs作用,分为2—70PEMFs作用组／未作用组、OVXPEMFs作用组侏作用组、SHAMPEMFs作用组／未作用组,分别进行CFU．F和CFU．GM培养观察。结果单独离体PEMFs作用时,与对照组相比,4个剂量组的CFU-GM减少,CFU．F增加;活体结合离体PEMFs作用时,剂量组的CFU—F均增加,而CFU—GM各组间均无显著差异。结论单独离体PEMFs作用时,PEMFs对体外培养的破骨细胞前体细胞有抑制作用,对成骨细胞前体细胞增殖有促进作用;活体结合离体PEMFs作用时,PEMFs对成骨细胞前体细胞增殖有促进作用,但未见对破骨细胞前体细胞的抑制作用。     

成骨细胞参与白细胞介素—1调节破骨细胞功能的实验研究

建立了成骨细胞和破骨细胞共同培养体系，探讨了白细胞介素－１（ＩＬ１）促进骨吸收的作用机理。研究发现，破骨细胞＋ＩＬ１组的骨吸收陷窝数目和面积，与单纯破骨细胞组比较，差异无显著性意义。破骨细胞＋成骨细胞＋ＩＬ１组，骨吸收陷窝数目和面积均显著增加，与破骨细胞＋ＩＬ１组及单纯破骨细胞对照组比较，差异均有显著性意义。提示ＩＬ１对破骨细胞缺乏直接作用，而是在成骨细胞介导下，发挥调节破骨细胞的骨吸收作用。     

力学载荷对破骨细胞凋亡的影响及其调节机制

破骨细胞是参与骨代谢的基本功能细胞之一.破骨细胞在骨重建过程中主要承担旧骨组织的破坏和吸收,因此,破骨细胞凋亡的微小变化都可能会改变骨重建的进程.调节破骨细胞凋亡的因素有很多,如雌激素、二磷酸盐等生物化学因素,但力学载荷对于破骨细胞生物学活性影响的研究相对较少.综述了力学载荷对破骨细胞生物学活性的影响以及细胞凋亡与破骨细胞凋亡的调节.     

成骨细胞和骨细胞的力学信号转导

背景:骨骼具有功能适应性的特点,骨骼细胞是力学信号敏感细胞,但细胞的力学信号转导功能是如何实现的,对骨骼如何调控仍不明确。 目的：了解成骨细胞和骨细胞的力学信号转导途径,为利用力学信号改善骨骼功能提供理论依据。 方法：应用计算机检索PubMed数据库2000-01/2011-03相关文献。英文检索词为“osteoblast,osteocyte,bone cells,mechanical stress”, 根据纳入标准共69篇文章进行综述,以此对骨骼细胞力学信号转导相关内容进行总结。 结果与结论：骨骼具有功能适应性的特点,骨骼细胞是力学信号敏感细胞,但细胞的力学信号转导功能是如何实现的,对骨骼具有怎样的调控仍不明确。研究表明,由于骨骼的结构特点和细胞位置,成骨细胞和骨细胞是最重要的力学敏感性细胞。力学信号在骨骼内的转导过程分为4个阶段：①力学偶联。②生化偶联。③信号的传递。④效应性细胞的反应。通过这4个阶段的作用,作用在骨骼上的应力信号转导为生物化学信号,并影响细胞的功能,最终导致骨骼组织出现相应的结构变化以适应应力环境的需要。对于力学信号在骨髓间充质干细胞中的调控机制还有待继续深入探索。     

不同浓度地塞米松体外对人成骨细胞和破骨细胞分化的影响

目的: 探讨地塞米松(DEX)体外对人成骨细胞(OBs)和破骨细胞(OCs)分化的影响。方法: 以DEX为主要成分的诱导剂体外刺激正常人骨髓间充质干细胞(MSCs),茜素红染色及碱性磷酸酶(ALP)定量法检测OBs间钙结节形成及OBs中ALP水平;改变DEX浓度后,再检测ALP水平以及用Western blotting检测OBs中磷酸化GSK-3β蛋白的表达;外源性核因子κB受体活化因子配基(RANKL)刺激人骨髓单个核细胞(BMMs)14 d后,用抗酒石酸酸性磷酸酶染色鉴定OCs形成情况、Western blotting检测BMMs中RANKL下游的信号途径;不同浓度DEX刺激MSCs 7 d后,用ELISA和Western blotting检测培养液中可溶性RANKL(sRANKL)水平及MSCs中RANKL蛋白表达。结果: 含0.1 μmol/L DEX的诱导剂刺激MSCs后可有钙结节形成,在DEX 0.001-0.1 μmol/L浓度范围内,OBs中ALP水平逐渐增高、磷酸化GSK-3β蛋白表达逐渐增强,当DEX浓度进一步增加后(0.1-10 μmol/L), ALP水平和磷酸化GSK-3β蛋白表达反而下降;外源性RANKL可以诱导BMMs分化为OCs,且BMMs中磷酸化IκBα、SPAK/JNK、p38 MAPK、p44/42 MAPK表达增强;在0.001-10 μmol/L浓度范围内,DEX刺激MSCs后,培养液中 sRANKL水平和MSCs中RANKL蛋白表达逐渐增高,且sRANKL水平和DEX浓度呈正相关(r=0.821,P<0.05)。结论: 在低浓度(0.001-0.1 μmol/L)范围内,DEX既促进OBs分化,又可促进OCs分化。在高浓度(0.1-10 μmol/L)范围内,仍能促进OCs分化,但失去了其对OBs的分化作用。     

PTH对破骨细胞骨吸收功能的影响及成骨细胞介导作用

采用分离、培养兔破骨细胞和成骨细胞的方法，体外研究甲状旁腺激素（ＰＴＨ）对破骨细胞骨吸收功能的影响，以及成骨细胞和破骨细胞之间的相互作用。结果表明，ＰＴＨ对破骨细胞的骨吸收功能无直接影响，但在成骨细胞参与下，ＰＴＨ对破骨细胞性骨吸收有明显的促进作用。说明成骨细胞在ＰＴＨ调节破骨细胞功能活动中有着重要的介导作用。     

低氧与成骨及破骨细胞代谢

背景：越来越多的研究发现低氧与骨质疏松症的发生密切相关。 目的：总结低氧对成骨及破骨细胞骨代谢的影响,进一步阐明低氧在骨质疏松症的发病机制。 方法：以“hypoxia,bone metabolism,osteoclasts,osteoblasts,COPD,high altitude,osteoporosis”为英文关键词,以“低氧,骨代谢,成骨细胞,破骨细胞,慢性阻塞性肺疾患,高原,骨质疏松”为中文关键词,检索2007/2011 PubMed数据库、万方资源数据库及维普期刊库有关低氧与骨代谢及骨质疏松症文献。 结果与结论：低氧可以促进破骨细胞的生成,增强破骨细胞骨吸收能力。低氧对成骨细胞生成的影响与氧浓度及低氧持续时间有关。低氧主要通过诱导低氧诱导因子的产生,而激活其下游一系列基因的表达,调节成骨细胞生成及其功能。慢性阻塞性肺疾患引起的骨质疏松症与低氧、糖皮质激素的应用、全身炎症反应及其他因素有关,高原环境下引起的骨质疏松主要与低氧有关。     

力学刺激在破骨细胞分化中的作用

骨组织细胞主要有成骨细胞、破骨细胞、骨细胞3种类型,与细胞外基质共同维持骨的结构完整性和功能性。破骨细胞专门负责骨吸收,通过释放酸性物质和蛋白水解酶降解骨基质,发挥骨吸收作用;通过与成骨细胞相互协调,共同维持骨稳态。破骨细胞增多,导致骨吸收增加,从而引起骨质疏松症等骨骼疾病;破骨细胞生成过少,将导致骨吸收减弱等相关疾病,例如骨硬化症。因此,对于破骨细胞功能的精确调控,在维持骨稳态的平衡中发挥极为关键的作用。既往研究多从生物化学角度解释和阐述各种生物因素对破骨细胞的调控。然而越来越多的研究证实,力学刺激在破骨细胞分化过程中发挥着重要的作用。本文着眼于力学刺激对破骨细胞分化的影响,讨论力学刺激在其中可能发挥的作用,并对该领域的新发现以及未来的发展进行探讨。     

Keratocan is Expressed by Osteoblasts and Can Modulate Osteogenic Differentiation

Keratocan is an extracellular matrix protein that belongs to the small leucine-rich proteoglycan family that also includes lumican, biglycan, decorin, mimecan, and fibromodulin. Members of this family are known to play a role in regulating cellular processes such as proliferation and modulation of osteoprogenitor lineage differentiation. The aims of this study were to evaluate the expression pattern of the keratocan within the osteoprogenitor lineage and to assess its role in regulating osteoblast maturation and function. Results from gene expression analyses of cells at different maturation stages within the osteoblast lineage indicate that keratocan is differentially expressed by osteoblasts and shows little or no expression by osteocytes. During primary osteoblast cultures, high keratocan mRNA expression was observed on day 14, whereas lower expression was detected at days 7 and 21. To assess the effects of keratocan on osteoprogenitor cell differentiation, we evaluated primary calvarial cell cultures from keratocan-deficient mice. The mineralization of calvarial osteoblast cultures derived from keratocan null (Kera–/–) mice was lower than in wild-type osteoblast cultures. Furthermore, analysis of RNA derived from Kera?/? calvarial cell cultures showed a reduction in the mature osteoblast differentiation markers, that is, bone sialoprotein and osteocalcin. In addition, we have evaluated the bone formation in keratocan-deficient mice. Histomorphometric analysis indicated that homozygous knockout mice have significantly decreased rates of bone formation and mineral apposition. Taken together, our results demonstrate the expression of keratocan by osteoblast lineage cells and its ability to modulate osteoblast function.     

力学刺激对3月龄骨质疏松大鼠成骨细胞增殖与合成功能的影响

探讨周期性双轴力学应变对成骨细胞增殖与分化合成功能的影响。将正常 3月龄雌性 SD大鼠和骨质疏松大鼠颅顶骨分离的成骨细胞分别在含 10 %胎牛血清的 F- 12培养液中培养 ,并接种在双轴力学应变装置中。当细胞生长至亚融合状态 (Subconfluence) ,给细胞施加力学刺激 ,频率为 1Hz,力学刺激分别为 4 0 0、10 0 0、4 0 0 0μ strain;作用时间分别为每天 30 m in,2、4、8h,共加载两天。以未受力学刺激的细胞为对照组 ,受力学刺激的细胞为实验组 ,并进行比较。采用流式细胞技术测定细胞增殖变化 ;采用同位素标记方法检测成骨细胞骨钙素、I型胶原 C端前肽 (PICP)和总蛋白的分泌量。结果表明 :1)在静态培养条件下 ,3ovx组与 3control组比较 ,其细胞功能活性无明显变化 ,但 3ovx组大鼠成骨细胞增殖活性明显增高 ,这与绝经后骨质疏松骨代谢的高转换率相一致。 2 )4 0 0、10 0 0 μstrain力学刺激可以促进 3control组成骨细胞 I型胶原、骨钙素和总蛋白的分泌量增加 ,促进成骨细胞的分化成熟 ;在 10 0 0μstrain力学刺激下 ,成骨细胞合成骨基质的能力增加最为明显。同时 ,在 4 0 0、10 0 0μstrain力学刺激的初期也可以促进成骨细胞的增殖 ,而促进成骨细胞的分化成熟的作用大于促进细胞增殖的作用。 3)在4 0 0 0 μ     

miR-194-3p调控模拟微重力条件下致成骨细胞功能异常的实验研究

目的 探讨模拟微重力环境下miR-194-3p调控成骨细胞功能变化的作用,为极端力学环境下成骨细胞的力学响应机制提供理论基础。方法 细胞旋转培养系统建立细胞水平微重力环境,分别采用MTT、RT-PCR、Western blot、荧光双染色法和茜素红染色法检测转染miR-194-3p抑制剂前后MC3T3-E1成骨细胞增殖、分化、凋亡和矿化的变化情况。结果 模拟微重力环境下miR-194-3p表达上调,成骨细胞的增殖、分化和矿化均受到一定程度的抑制,同时促进了成骨细胞的凋亡。转染miR-194-3p抑制剂后,miR-194-3p表达显著下调,且能部分逆转由微重力导致的细胞成骨细胞增殖减弱、成骨分化标志物如ALP、OCN和COL-I基因和蛋白表达降低、骨矿化结节减少和成骨细胞凋亡数目增加的情况,说明miR-194-3p能有效改善微重力暴露下成骨细胞功能异常的情况。 结论 模拟微重力环境下,miR-194-3p可能作为一种负调控因子,通过调控成骨细胞功能参与其力学响应的进程。     

力学刺激诱导骨髓间充质干细胞选择分化的研究进展

机体细胞／组织处于复杂的力学环境中，力学刺激对细胞的形态、发育和功能起着重要的调节作用。骨髓间充质干细胞的增殖、选择分化受多种力学因素的影响，而且力学刺激的大小、方式以及作用时间对骨髓间充质干细胞定向分化的调节作用不尽相同。作者就力学因素对骨髓间充质干细胞选择分化的调节作用进行简要的综述。     

Reviewer's comments on the paper entitled: “Correlation of the arrangement pattern of enamel rods and secretory ameloblasts in pig and monkey teeth: A possible role of the terminal webs in ameloblast movement during secretion,” by S. Nishikawa

The ultrastructural distribution of two noncollagenous proteins, osteopontin (OPN) and osteocalcin (OC), originally extracted from bone matrix and proposed to play an important role in bone formation, was examined in the matrices of bone and cartilage from embryonic and postnatal chicken tibial growth plates by high-resolution immunocytochemistry using the colloidal gold technique. In bone, immunolabeling patterns using polyclonal antibodies against chicken OPN and OC were generally similar in that both showed an intense, but regionally variable, labeling of mineralized bone matrix and small mineralization loci dispersed throughout the osteoid and containing prominent condensed organic material. Unmineralized osteoid showed weak-to-moderate labeling. In the mineralized bone matrix proper, labeling was predominantly associated with amorphous, electron-dense patches of organic material among the collagen fibrils. In growth plate cartilage, both proteins first appeared related to calcified cartilage in the hypertrophic zone, although the labeling patterns were somewhat different. For OPN, gold particles were mostly associated with an organic lamina limitans-like density containing condensed, filamentous organic matrix at the periphery of small nodules and large masses of calcified cartilage, with additional moderate labeling throughout the interior of the calcified cartilage. For OC, labeling was observed over filamentous structures throughout the calcified cartilage matrix, with some, but less, labeling at the periphery. In the lowermost zones of the growth plate, the major reaction using both antibodies was found over a layer of dense, amorphous organic material at the periphery of the calcified cartilage at the future bone/calcified cartilage interface, a labeling pattern that persisted following bone deposition at these sites. OPN and to a lesser extent OC were also concentrated in cement (resting, reversal) lines. Throughout the bone and cartilage of the tibia, cells of both the osteoblastic and the osteoclastic lineages were found directly apposed to labeled surfaces and lamina limitans of organic matrix containing OPN and OC. In summary, it is concluded form the immunocytochemical data presented here that the association of OPN and OC with mineralized regions of the extracellular matrices of bone and cartilage and the accumulation of these proteins at tissue surfaces and interfaces are consistent with the hypotheses that they play a role in the extracellular mineralization process per se and/or that they may mediate cell adhesion and dynamics.© Willey-Liss, Inc.     

Mechanical and biological properties of photocurable oligolactide-HA composites investigated under accelerated degradation

The major concern related to biodegradable bone substitute materials is the loss of mechanical strength which can be undesirable when occurring too quickly before new bone formation. In this study, the multifunctional lactide oligomers having 2, 3, and 4 arms end capped with methacrylate groups were synthesized with the aim of improving the degradation properties. Their composites with hydroxyapatite (HA) were photopolymerized and subjected to accelerated degradation at 60 °C. The results showed that increasing number of arms significantly improved thermal and mechanical properties as well as biocompatibility of the composites. All composites although varying in number of arms had similar levels of bone-specific gene expression and calcification indicating their equal bioactivity in supporting bone formation. The high HA content in the composites was proposed to be responsible for enhanced osteoblast response, and this tended to suppress the effects of polymeric structure.     

力学因素对血管内皮细胞成血管影响及机制的研究进展

血管内皮细胞的成血管能力受多重力学因素的影响。力学因素通过调控血管内皮细胞生长的微环境,引导细胞骨架重排,介导细胞内信号转导,影响细胞迁移、连接等行为,进而调控其成血管水平。然而不同性质的力学刺激对其成血管能力的调节作用不尽相同。综述及讨论5种力学因素（剪切力、牵张力、低强度脉冲式超声、微重力和材料性质）对血管内皮细胞成血管影响的研究工作及进展,为深入研究血管生物力学提供基础与思路。     

鼻腔内机械振荡刺激对健康人群静息态脑电图相对功率及有效连接的影响

鼻腔内机械振荡刺激(iMVS)是一种新型的无创神经刺激技术,可提升边缘系统内在功能活性从而改善自主神经平衡.通过分析iMVS对健康人群脑电图(EEG)相对功率以及EEG有效连接的影响,探索iMVS的神经生理机制.将22名健康成年被试随机均分为刺激组与对照组,并对11名刺激组被试两侧鼻腔各进行10 min的iMVS,11...