MicroRNA调控成骨细胞增殖、凋亡的研究进展

微小RNA( microRNA)是一类非编码小分子RNA,在基因表达调控中起重要作用,它通过与靶mRNA的特异性结合,导致靶mRNA降解或者抑制其翻译,对基因进行转录后调控,从而控制细胞的增殖、分化、凋亡等,参与疾病的发生发展。成骨细胞是骨形成过程中的重要细胞,其数量或功能的改变明显影响骨代谢。近年来.microRNA与骨代谢的关系备受关注,诸多研究表明microRNA在成骨细胞的分化中发挥重要调控作用,但其调节成骨细胞增殖和凋亡的研究相对较少。本文就 microRNA调控成骨细胞增殖、凋亡的研究进展进行综述。     

自噬对成骨细胞调控作用的研究进展

自噬是一种溶酶体降解途径,负责不必要细胞器和蛋白质等的降解和再循环,同时也能破坏细胞内的病原体。自噬对于维持机体新陈代谢的平衡具有重要作用,并且可调控细胞的生长、分化。成骨细胞是骨形成的主要功能细胞,主要负责骨基质的合成、分泌和矿化。成骨细胞活性或功能异常会导致骨质疏松、股骨头坏死、骨折愈合延缓等疾病。最新研究表明自噬在维持骨骼的动态平衡中具有关键性的调控作用。在间充质干细胞向成骨细胞分化的过程中以及在地塞米松、双膦酸盐等药物干预下,自噬呈现不同水平,成骨细胞的活性、增殖、分化和功能也因此产生相应的变化,进而影响骨形成和骨重塑。此外在骨质疏松和骨折愈合迟缓等骨疾病中,自噬也可通过调控成骨细胞的功能活性对疾病的进程产生影响。因此本文综述国内外有关自噬和成骨细胞的相关文献报道,旨在阐明自噬对成骨细胞调控作用。     

成骨过程中微小RNAs调控作用的研究进展

目的 对微小RNAs(microRNAs,miRNAs)在成骨过程中的调控作用及作用机制的研究现状、存在的争议以及研究方向作一综述.方法 广泛查阅近年来有关成骨过程中miRNAs的调控作用及作用机制的文献,进行总结与分析.结果 miRNAs是近来成骨研究的热点,越来越多资料显示其在骨化过程中发挥重要作用,但确切机制尚未清楚.结论 通过应用miRNAs技术促进成骨细胞分化,具有巨大的应用前景,同时将可能获取成骨细胞分化中的miRNAs调控机制,也有利于建立成骨效果比较的研究模型.     

成骨细胞分化调控机制研究新进展

成骨细胞的分化是骨发生、骨形成的前提.成骨干细胞经过一步或几步分化为前成骨细胞(具有向成骨细胞和软骨细胞分化的双向分化潜能),再继续分化为有功能的成骨细胞和软骨细胞.成骨细胞在分化过程中受CTGF、FGF-2、BMP、Dlx-5、Runx2、Osx、Sox9、TGF-β1、TNF-α等多种因子的调控,调控过程相互联系,相互影响.     

成骨细胞分化调控因子研究进展

成骨细胞具有维持骨骼结构,调控骨矿化和破骨细胞的功能,其分化受多种因子影响.Wnt信号转导通路中Wnt- 10b、Wnt-3a蛋白与成骨细胞分化关系密切;骨形态发生蛋白(BMP)信号通路中BMP-2、BMP-13等蛋白双向调控成骨细胞分化,维护骨量平衡,BMP还能通过调控Osx、Smad1等促进成骨细胞分化;3磷脂酰肌...     

线粒体调控成骨细胞功能的研究进展

成骨细胞是骨修复重建的关键细胞，其增殖、分化、矿化的异常是骨质疏松症等骨代谢疾病的主要发病原因。线粒体在成骨细胞成骨功能中的调控作用不容忽视。近年研究发现，线粒体调控成骨细胞的能力，主要和线粒体氧化磷酸化、线粒体生物发生、线粒体动力学、线粒体自噬介导线粒体数量和功能的维持、为细胞提供能量及信号传导密切相关。本文综述了近年来线粒体调控成骨细胞功能的相关研究进展。     

miRNA在骨重建中的作用

微小RNA(micro RNA,miRNA)是一类具有组织特异性或发育阶段特异性表达特征的非编码调控小RNA,近年来,miRNA与骨形成和代谢的关系已成为研究热点之一,许多研究发现miRNA在骨代谢中的调控作用巨大。部分miRNA能够调节骨重建过程中的血管生成以及成骨细胞、破骨细胞的分化,通过改变相关miRNA表达水平进而深入研究miRNA在骨重建中的调控作用,同时miRNA可作为早期检测骨代谢疾病的生物标志物。本文通过对已知的miRNA在骨重建中血管生成及成骨细胞、破骨细胞中生物学和骨病理学作用机制的总结,说明其在骨重建过程中的重要作用。基于miRNA在骨重建中的调控作用,并在骨代谢相关疾病的临床实践中开辟新的领域,进而对骨代谢疾病有治疗作用。     

线粒体对间充质干细胞成骨分化功能的研究

间充质干细胞成骨分化能力异常减弱和成骨细胞数量异常下降都会导致生物体内骨代谢紊乱，诱导骨质疏松症的发生。线粒体在MSC多能性保持和成骨分化过程中具有十分重要的作用，通过能量代谢、抗氧化途径、代谢相关信号通路、线粒体生物发生、线粒体动力学和线粒体自噬等参与间充质干细胞成骨分化的调控，形成了复杂的调节网络。本文综述了MSC成骨分化中线粒体的重要功能和作用，以及部分通过调节线粒体功能发挥抗骨质疏松治疗的药物，为进一步探讨间充质干细胞成骨分化功能失调的机制提供新的思路，为临床治疗骨质疏松症提供新的靶点。     

BMPs及其相关microRNAs在MSC向成骨细胞 分化过程中的作用

目的间充质干细胞(MSCs)向成骨细胞分化是目前组织工程和骨愈合研究的热点。已有大 量文献报道骨诱导形成蛋白（BMP)在该过程中的作用,随着微小RNA( microRNA,miRNA)的发现,其 对BMP在MSC向成骨细胞诱导分化过程中所起的调控作用也日益受到重视。作者归纳总结了 BMIP及其相关miRNA在MSC向成骨细胞分化过程中的作用,以及一些常用生物材料在诱导MSCs 向成骨细胞分化过程中,对BMP及相关miRNA的影响。为进一步的研究提供了借鉴和参考。     

miRNA与骨代谢

microRNA(miRNA)是一类转录水平具有调控功能的非编码RNA,能够调控多种基因的表达,其在骨代谢过程以及代谢性骨病中起着重要作用。本文综述了miRNA对成骨细胞、破骨细胞的作用以及miRNA在骨质疏松发病机制中的作用,为未来寻找新的骨代谢相关疾病诊断标记及治疗靶点提供方向。     

Microtubule assembly affects bone mass by regulating both osteoblast and osteoclast functions: Stathmin deficiency produces an osteopenic phenotype in mice

Cytoskeleton microtubules regulate various cell signaling pathways that are involved in bone cell function. We recently reported that inhibition of microtubule assembly by microtubule‐targeting drugs stimulates osteoblast differentiation and bone formation. To further elucidate the role of microtubules in bone homeostasis, we characterized the skeletal phenotype of mice null for stathmin, an endogenous protein that inhibits microtubule assembly. In vivo micro–computed tomography (µCT) and histology revealed that stathmin deficiency results in a significant reduction of bone mass in adult mice concurrent with decreased osteoblast and increased osteoclast numbers in bone tissues. Phenotypic analyses of primary calvarial cells and bone marrow cells showed that stathmin deficiency inhibited osteoblast differentiation and induced osteoclast formation. In vitro overexpression studies showed that increased stathmin levels enhanced osteogenic differentiation of preosteoblast MC3T3‐E1 cells and mouse bone marrow–derived cells and attenuated osteoclast formation from osteoclast precursor Raw264.7 cells and bone marrow cells. Results of immunofluorescent studies indicated that overexpression of stathmin disrupted radial microtubule filaments, whereas deficiency of stathmin stabilized the microtubule network structure in these bone cells. In addition, microtubule‐targeting drugs that inhibit microtubule assembly and induce osteoblast differentiation lost these effects in the absence of stathmin. Collectively, these results suggest that stathmin, which alters microtubule dynamics, plays an essential role in maintenance of postnatal bone mass by regulating both osteoblast and osteoclast functions in bone. © 2011 American Society for Bone and Mineral Research     

Wnt/β-catenin信号通路主要因子与成骨细胞研究进展

经典Wnt/β-catenin信号通路在成骨细胞的增殖、分化及骨形成过程中起关键作用.Wnt信号通路中主要因子Wnt配体、β-catenin及转录因子Runx2表达与功能的改变,将会影响成骨细胞的增殖、分化、骨基质的形成和矿化,进而导致骨量的变化.通路中不同因子在成骨细胞分化与成熟的过程中所起作用又有所不同,而且在此过程中又会受到其它因素的影响,进而增强或减弱成骨细胞分化与成熟的进程.     

Suppression of autophagy by FIP200 deletion leads to osteopenia in mice through the inhibition of osteoblast terminal differentiation

Autophagy is a conserved lysosomal degradation process that has important roles in both normal human physiology and disease. However, the function of autophagy in bone homeostasis is not well understood. Here, we report that autophagy is activated during osteoblast differentiation. Ablation of focal adhesion kinase family interacting protein of 200 kD (FIP200), an essential component of mammalian autophagy, led to multiple autophagic defects in osteoblasts including aberrantly increased p62 expression, deficient LC3‐II conversion, defective autophagy flux, absence of GFP‐LC3 puncta in FIP200‐null osteoblasts expressing transgenic GFP‐LC3, and absence of autophagosome‐like structures by electron microscope examination. Osteoblast‐specific deletion of FIP200 led to osteopenia in mice. Histomorphometric analysis revealed that the osteopenia was the result of cell‐autonomous effects of FIP200 deletion on osteoblasts. FIP200 deletion led to defective osteoblast terminal differentiation in both primary bone marrow and calvarial osteoblasts in vitro. Interestingly, both proliferation and differentiation were not adversely affected by FIP200 deletion in early cultures. However, FIP200 deletion led to defective osteoblast nodule formation after initial proliferation and differentiation. Furthermore, treatment with autophagy inhibitors recapitulated the effects of FIP200 deletion on osteoblast differentiation. Taken together, these data identify FIP200 as an important regulator of bone development and reveal a novel role of autophagy in osteoblast function through its positive role in supporting osteoblast nodule formation and differentiation. © 2013 American Society for Bone and Mineral Research.     

Oscillatory fluid flow affects human marrow stromal cell proliferation and differentiation.

Mechanical loading is an important regulator of bone formation and bone loss. Decreased osteoblast number and function are important cellular mechanisms by which mechanical disuse leads to decreased bone formation. Decreased osteoblast number may be a result of decreased osteoprogenitor proliferation, differentiation, or both. However, the effects of cellular level physical signals on osteoprogenitors are not well understood. In this study, we examined the effects of loading induced oscillatory fluid flow (OFF), a potent regulator of osteoblastic cell function, on marrow stromal cells (MSCs). MSCs subjected to OFF exhibited increased intracellular Ca2+ mobilization. In addition, MSCs exhibited increased proliferation and increased mRNA levels for osteopontin and osteocalcin genes. Collagen I and core binding factor 1 mRNA levels did not change. MSCs subjected to OFF also exhibited decreased alkaline phosphatase activity. These results suggest that MSCs are mechanosensitive and that Ca2+ may play a role in the signaling pathway.     

A role for N-cadherin in the development of the differentiated osteoblastic phenotype.

Cadherins are a family of cell surface adhesion molecules that play an important role in tissue differentiation. A limited repertoire of cadherins has been identified in osteoblasts, and the role of these molecules in osteoblast function remains to be elucidated. We recently cloned an osteoblast-derived N-cadherin gene from a rat osteoblast complementary DNA library. After in situ hybridization of rat bone and immunohistochemistry of human osteophytes, N-cadherin expression was localized prominently in well-differentiated (lining) osteoblasts. Northern blot hybridization in primary cultures of fetal rat calvaria and in human SaOS-2 and rat ROS osteoblast-like cells showed a relationship between N-cadherin messenger RNA expression and cell-to-cell adhesion, morphological differentiation, and alkaline phosphatase and osteocalcin gene expression. Treatment with a synthetic peptide containing the His-Ala-Val (HAV) adhesion motif of N-cadherin significantly decreased bone nodule formation in primary cultures of fetal rat calvaria and inhibited cell-to-cell contact in rat osteoblastic TRAB-11 cells. HAV peptide also regulated the expression of specific genes such as alkaline phosphatase and the immediate early gene zif268 in SaOS-2 cells. Transient transfection of SaOS-2 cells with a dominant-negative N-cadherin mutant (NCADdeltaC) significantly inhibited their morphological differentiation. In addition, aggregation of NCTC cells derived from mouse connective tissue stably transfected with osteoblast-derived N-cadherin was inhibited by either treatment with HAV or transfection with NCADdeltaC. Together, these results strongly support a role for N-cadherin, in concert with other previously identified osteoblast cadherins, in the late stages of osteoblast differentiation.