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1.
BMP—2和BMP—4基因结构及调控的研究进展 总被引:1,自引:0,他引:1
岳文 《国外医学:分子生物学分册》1999,21(2):85-88
BMP-4基因组包括5个外显子,不同组织来源的BMP-4CDNA采用不同的启动子,BMP-4基因上有COUP-TF1的调节作用位点。BMP-2基因组有2个外显子,不同组织来源的BMP-2CDNA亦采用不同的启动子,BMP-2基因上有P53的作用位点。 相似文献
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降钙素与降钙素基因相关肽(CT/CGRP)基因编码一组多肽,即降钙素(CT)、降钙素的N端肽和C端肽、降钙素基因相关肽(CGRP)及淀粉不溶素(Amylin)。CT/CGRP基因转录而成的mRNA前体,在不同组分中通过选择性加工形成CT mRNA或CGRPmRNA,再通过翻译及蛋白质加工,最后形成成熟的降钙素或降钙素基因相关肽。本简单介绍一下降钙素的基因结构及表达调控方面的研究进展。 相似文献
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小麦等谷类植物种子贮藏蛋白基因的表达与调控 总被引:3,自引:0,他引:3
高等植物在成熟期的主要生理过程是将蛋白质、淀粉和脂肪等贮藏在种子中。贮藏在种子中的蛋白质称为种子贮藏蛋白。小麦、水稻、玉米等粮食作物是人类和家畜摄取蛋白质的重要来源。研究贮藏蛋白基因在种子发育过程中的表达机制,是进一步应用生物技术改良作物的基础工作。1谷物 相似文献
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成簇基因的时空表达调控 总被引:4,自引:0,他引:4
成簇基因具有不同单个基因的特性,同一簇内基因大多有类似的结构,功能以及表达模式,基因之间时空表达模式及表达量高度协调,提示同一簇基因是作为统一整体进行调节的,具有共同的调节机制。基因成簇排列是实现基因时空协调表表达的基础,是遗传信息的一种高级组织形式,具有强大的进化优势,要揭示成簇基因表达调控的基本规律,应从顺式作用元件,反式作用因子,染色质等层次,进行整体的以及多基因相互作用的研究,这些机制的阐 相似文献
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神经肽Y的基因及其表达调控 总被引:1,自引:0,他引:1
神经肽酷氨酸是一种含36个氨基酸残基的生物活性多肽,在体内具有收缩血管,影响激素分泌,调节生物节律及摄食行为等多种生物学功能。本从NPY cDNA克隆,基因结构与功能关系以及多种因素对其基因表达的调节等方面作一综述。 相似文献
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植物伸展蛋白的基因及其表达的调控 总被引:2,自引:0,他引:2
植物细胞壁中存在多种伸展蛋白。它们由伸展蛋白多基因族编码。调节伸展蛋白基因表达的因素有遗传密码使用的倾向性、发育程序、机械损伤、乙烯、病原和植物抗毒素诱导剂等。 相似文献
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韩根成 《国外医学:分子生物学分册》1999,21(2):80-84
CD59基因含5个外显子,属于UPAR/Ly-6超家族成员。该家族基因结构保守,但它们表达蛋白质具有广泛的生物学功能,CD59分子有组成性和诱导性表达两种表达方式,顺式作用元件及反式作用蛋白质协调作用决定着基因表达的特生。 相似文献
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Kazuharu Irie Sadakazu Ejiri Yasunori Sakakura Toru Shibui Toshihiko Yajima 《The journal of histochemistry and cytochemistry》2008,56(6):561-567
The morphology of the osteocyte changes during the cell's lifetime. Shortly after becoming buried in the matrix, an osteocyte is plump with a rich rough endoplasmic reticulum and a well-developed Golgi complex. This "immature" osteocyte reduces its number of organelles to become a "mature" osteocyte when it comes to reside deeper in the bone matrix. We hypothesized that mineralization of the surrounding matrix is the trigger for osteocyte maturation. To verify this, we prevented mineralization of newly formed matrix by administration of 1-hydroxyethylidene-1,1-bisphosphonate (HEBP) and then examined the morphological changes in the osteocytes in rats. In the HEBP group, matrix mineralization was disturbed, but matrix formation was not affected. The osteocytes found in the unmineralized matrix were immature. Mature osteocytes were seen in the corresponding mineralized matrix in the control group. The immature osteocytes in the unmineralized matrix failed to show immunoreactivity with anti-sclerostin antibody, whereas mature osteocytes in the mineralized matrix showed immunoreactivity in both control and HEBP groups. These findings suggest that mineralization of the matrix surrounding the osteocyte is the trigger for cytodifferentiation from a plump immature form to a mature osteocyte. The osteocyte appears to start secreting sclerostin only after it matures in the mineralized bone matrix. 相似文献
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Verena Boschert Eva‐Maria Muth Achim Knappik Christian Frisch Thomas D. Mueller 《Acta Crystallographica. Section F, Structural Biology Communications》2015,71(4):388-392
The secreted cystine‐knot protein sclerostin was first identified from genetic screening of patients suffering from the rare bone‐overgrowth diseases sclerosteosis and van Buchem disease. Sclerostin acts a negative regulator of bone growth through inhibiting the canonical Wnt signalling cascade by binding to and blocking the Wnt co‐receptor LRP5/6. Its function in blocking osteoblastogenesis makes it an important target for osteoanabolic therapy approaches to treat osteoporosis, which is characterized by a progressive decrease in bone mass and density. In this work, the production, crystallization and preliminary X‐ray diffraction data analysis of a sclerostin‐neutralizing human Fab antibody fragment, AbD09097, obtained from a naive antibody library are reported. Crystals of the Fab AbD09097 belonged to space group P21, with unit‐cell parameters a = 45.19, b = 78.49, c = 59.20 Å, β = 95.71° and diffracted X‐rays to a resolution of 1.8 Å. 相似文献
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硬化蛋白基因在淇河鲫成鱼不同肌间骨相邻肌组织的表达差异分析 总被引:1,自引:0,他引:1
为探究硬化蛋白(sclerostin, SOST)基因在淇河鲫肌间骨不同分布位置中的作用,以淇河鲫成鱼为研究对象,对其肌间骨的形态与分布进行了统计,并在此基础上利用qRT-PCR技术检测SOST基因在淇河鲫背部和尾部肌肉中的mRNA表达,通过Western印迹和免疫组织化学技术检测SOST蛋白的表达定位情况。结果显示:淇河鲫肌间骨包括髓弓小骨和脉弓小骨,髓弓小骨为56~58根,位于淇河鲫背部肌肉的肌隔中,脉弓小骨27~28根,分布于泄殖孔之后的肌隔中。背部肌肉SOST的mRNA表达水平显著高于尾部肌肉(P < 0.05)。与mRNA表达水平相比,背部肌肉和尾部肌肉中SOST蛋白呈现相同表达趋势。免疫组织化学结果显示SOST在肌隔组织中特异性表达,并且在背部肌肉中的表达强烈,尾部肌肉中没有阳性反应。上述结果表明,SOST在淇河鲫肌间骨的背部和尾部肌肉中存在差异性表达,从而影响肌隔组织中肌间骨的骨化,对背部和尾部肌间骨形态发生产生影响。 相似文献
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Eric E. Beier Tzong-jen Sheu Deborah Dang Jonathan D. Holz Resika Ubayawardena Philip Babij J. Edward Puzas 《The Journal of biological chemistry》2015,290(29):18216-18226
Exposure to lead (Pb) from environmental sources remains an overlooked and serious public health risk. Starting in childhood, Pb in the skeleton can disrupt epiphyseal plate function, constrain the growth of long bones, and prevent attainment of a high peak bone mass, all of which will increase susceptibility to osteoporosis later in life. We hypothesize that the effects of Pb on bone mass, in part, come from depression of Wnt/β-catenin signaling, a critical anabolic pathway for osteoblastic bone formation. In this study, we show that depression of Wnt signaling by Pb is due to increased sclerostin levels in vitro and in vivo. Downstream activation of the β-catenin pathway using a pharmacological inhibitor of GSK-3β ameliorates the Pb inhibition of Wnt signaling activity in the TOPGAL reporter mouse. The effect of Pb was determined to be dependent on sclerostin expression through use of the SOST gene knock-out mice, which are resistant to Pb-induced trabecular bone loss and maintain their mechanical bone strength. Moreover, isolated bone marrow cells from the sclerostin null mice show improved bone formation potential even after exposure to Pb. Also, our data suggest that the TGFβ canonical signaling pathway is the mechanism by which Pb controls sclerostin production. Taken together these results support our hypothesis that the osteoporotic-like phenotype observed after Pb exposure is, in part, regulated through modulation of the Wnt/β-catenin pathway. 相似文献
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Zai Hang Zhang Xin Yu Jia Jing Yi Fang Hao Chai Qun Huang Chang She Peng Jia De Chun Geng Wei Xu 《Journal of cellular and molecular medicine》2020,24(7):4233-4244
The increase in bone resorption and/or the inhibition of bone regeneration caused by wear particles are the main causes of periprosthetic osteolysis. The SOST gene and Sclerostin, a protein synthesized by the SOST gene, are the characteristic marker of osteocytes and regulate bone formation and resorption. We aimed to verify whether the SOST gene was involved in osteolysis induced by titanium (Ti) particles and to investigate the effects of SOST reduction on osteolysis. The results showed osteolysis on the skull surface with an increase of sclerostin levels after treated with Ti particles. Similarly, sclerostin expression in MLO-Y4 osteocytes increased when treated with Ti particles in vitro. After reduction of SOST, local bone mineral density and bone volume increased, while number of lytic pores on the skull surface decreased and the erodibility of the skull surface was compensated. Histological analyses revealed that SOST reduction increased significantly alkaline phosphatase- (ALP) and osterix-positive expression on the skull surface which promoted bone formation. ALP activity and mineralization of MC3T3-E1 cells also increased in vitro when SOST was silenced, even if treated with Ti particles. In addition, Ti particles decreased β-catenin expression with an increase in sclerostin levels, in vivo and in vitro. Inversely, reduction of SOST expression increased β-catenin expression. In summary, our results suggested that reduction of SOST gene can activate the Wnt/β-catenin signalling pathway, promoting bone formation and compensated for bone loss induced by Ti particles. Thus, this study provided new perspectives in understanding the mechanisms of periprosthetic osteolysis. 相似文献
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Hao Chai Zai Hang Zhang Jing Yi Fang Chang She De Chun Geng Wei Xu 《Journal of cellular and molecular medicine》2022,26(15):4371
The mechanism underlying induction of periprosthetic osteolysis by wear particles remains unclear. In this study, cultured MLO‐Y4 osteocytic cells were exposed to different concentrations of titanium (Ti) particles. The results showed that Ti particles increased expression of the osteocytic marker SOST/sclerostin in a dose‐dependent manner, accelerated apoptosis of MLO‐Y4 cells, increased the expression of IL‐6, TNF‐α and connexin 43. SOST silence alleviated the increase of MLO‐Y4 cells apoptosis, decreased the expression of IL‐6, TNF‐α and connexin 43 caused by Ti particles. The different co‐culture systems of MLO‐Y4 cells with MC3T3‐E1 osteoblastic cells were further used to observe the effects of osteocytic cells'' changes induced by Ti particles on osteoblastic cells. MLO‐Y4 cells treated with Ti particles inhibited dramatically differentiation of MC3T3‐E1 cells mostly through direct cell‐to‐cell contact. SOST silence attenuated the inhibition effects of Ti‐induced MLO‐Y4 on MC3T3‐E1 osteoblastic differentiation, which ALP level and mineralization of MC3T3‐E1 cells increased and the expression of ALP, OCN and Runx2 increased compared to the Ti‐treated group. Taken together, Ti particles had negative effects on MLO‐Y4 cells and the impact of Ti particles on osteocytic cells was extensive, which may further inhibit osteoblastic differentiation mostly through intercellular contact directly. SOST/sclerostin plays an important role in the process of mutual cell interaction. These findings may help to understand the effect of osteocytes in wear particle‐induced osteolysis. 相似文献
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Judex S Zhong N Squire ME Ye K Donahue LR Hadjiargyrou M Rubin CT 《Journal of cellular biochemistry》2005,94(5):982-994
Identifying the molecular mechanisms that regulate bone's adaptive response to alterations in load bearing may potentiate the discovery of interventions to curb osteoporosis. Adult female mice (BALB/cByJ) were subjected to catabolic (disuse) and anabolic (45 Hz, 0.3g vibration for 10 min/day) signals, and changes in the mRNA levels of thirteen genes were compared to altered indices of bone formation. Age-matched mice served as controls. Following 4 days of disuse, significant (P = 0.05) decreases in mRNA levels were measured for several genes, including collagen type I (-55%), osteonectin (-44%), osterix (-36%), and MMP-2 (-36%) all of which, after 21 days, had normalized to control levels. In contrast, expression of several genes in the vibrated group, which failed to show significant changes at 4 days, demonstrated significant increases after 21 days, including inducible nitric oxide synthase (iNOS) (39%, P = 0.07), MMP-2 (54%), and receptor activator of the nuclear factor kB ligand (RANKL) (32%). Correlations of gene expression patterns across experimental conditions and time points allowed the functional clustering of responsive genes into two distinct groups. Each cluster's specific regulatory role (formation vs. resorption) was reinforced by the 60% suppression of formation rates caused by disuse, and the 55% increase in formation rates stimulated by mechanical signals (P < 0.05). These data confirm the complexity of the bone remodeling process, both in terms of the number of genes involved, their interaction and coordination of resorptive and formative activity, and the temporal sensitivity of the processes. More detailed spatial and temporal correlations between altered mRNA levels and tissue plasticity may further delineate the molecules responsible for the control of bone mass and morphology. 相似文献
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Monici M Fusi F Paglierani M Marziliano N Cogoli A Pratesi R Bernabei PA 《Journal of cellular biochemistry》2006,98(1):65-80
Gravity acts permanently on organisms as either static or dynamic stimulation. Understanding the influence of gravitational and mechanical stimuli on biological systems is an intriguing scientific problem. More than two decades of life science studies in low g, either real or modeled by clinostats, as well as experimentation with devices simulating different types of controlled mechanical stimuli, have shown that important biological functions are altered at the single cell level. Here, we show that the human leukemic line FLG 29.1, characterized as an osteoclastic precursor model, is directly sensitive to gravitational unloading, modeled by a random positioning machine (RPM). The phenotypic expression of cytoskeletal proteins, osteoclastic markers, and factors regulating apoptosis was investigated using histochemical and immunohistochemical methods, while the expression of the corresponding genes was analyzed using RT-PCR. A quantitative bone resorption assay was performed. Autofluorescence spectroscopy and imaging were applied to gain information on cell metabolism. The results show that modeled hypogravity may trigger both differentiation and apoptosis in FLG 29.1 cells. Indeed, when comparing RPM versus 1 x g cultures, in the former we found cytoskeletal alterations and a marked increase in apoptosis, but the surviving cells showed an osteoclastic-like morphology, overexpression of osteoclastic markers and the ability to resorb bone. In particular, the overexpression of both RANK and its ligand RANKL, maintained even after return to 1 x g conditions, is consistent with the firing of a differentiation process via a paracrine/autocrine mechanism. 相似文献
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Chufang Liao Yanjing Ou Yun Wu Yi Zhou Shanshan Liang Yining Wang 《Journal of cellular physiology》2019,234(11):20779-20789