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三磷酸腺苷(ATP)和腺苷作为成骨样细胞(MC3T3-E1)的促分裂原。

ATP and adenosine act as a mitogen for osteoblast-like cells (MC3T3-E1).

作者信息

Shimegi S

机构信息

Faculty of Health and Sport Sciences, Osaka University, Japan.

出版信息

Calcif Tissue Int. 1996 Feb;58(2):109-13. doi: 10.1007/BF02529732.

DOI:10.1007/BF02529732
PMID:8998680
Abstract

Extracellular ATP, and to a lesser extent adenosine, an ATP metabolite, stimulated cell proliferation in osteoblast-like cells (MC3T3-E1). ATP increased cytosolic Ca2+ due to Ca2+ mobilization from intracellular storage in the same concentration range of the nucleotide as that effective for DNA synthesis, suggesting the mediation of the phospholipase C/Ca2+ system in the mitogenic action. Since adenosine induced no Ca2+ mobilization, P2-purinergic receptor appears to be associated with ATP actions. The growth-promoting effect of ATP was not inhibited by H7, a protein kinase C inhibitor, and indomethacin, a cyclooxygenase inhibitor, indicating no involvement of activation of protein kinase C and production of prostaglandins in ATP-induced mitogenic signals. Either ATP or adenosine remarkably and synergistically potentiated platelet derived growth factor-induced DNA synthesis. These findings suggest that extracellular ATP and adenosine may play a physiological role in the regulation of bone formation.

摘要

细胞外ATP以及程度稍轻的ATP代谢产物腺苷,可刺激成骨样细胞(MC3T3-E1)的细胞增殖。在与DNA合成有效浓度范围相同的核苷酸浓度下,ATP由于细胞内储存的Ca2+动员而增加了胞质Ca2+,这表明磷脂酶C/Ca2+系统参与了有丝分裂作用的介导。由于腺苷未诱导Ca2+动员,P2-嘌呤能受体似乎与ATP的作用有关。ATP的促生长作用不受蛋白激酶C抑制剂H7和环氧化酶抑制剂吲哚美辛的抑制,这表明蛋白激酶C的激活和前列腺素的产生不参与ATP诱导的有丝分裂信号。ATP或腺苷均可显著且协同增强血小板衍生生长因子诱导的DNA合成。这些发现表明,细胞外ATP和腺苷可能在骨形成的调节中发挥生理作用。

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Calcif Tissue Int. 1996 Feb;58(2):109-13. doi: 10.1007/BF02529732.
2
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Extracellular ATP augments mesangial cell growth induced by multiple growth factors.细胞外ATP增强多种生长因子诱导的系膜细胞生长。
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本文引用的文献

1
Osteoblast-like cells have a variable mixed population of purino/nucleotide receptors.成骨样细胞具有嘌呤/核苷酸受体的可变混合群体。
FEBS Lett. 1993 Aug 9;328(1-2):209-14. doi: 10.1016/0014-5793(93)80994-6.
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Permissive stimulation of Ca(2+)-induced phospholipase A2 by an adenosine receptor agonist in a pertussis toxin-sensitive manner in FRTL-5 thyroid cells: a new 'cross-talk' mechanism in Ca2+ signalling.在FRTL-5甲状腺细胞中,腺苷受体激动剂以百日咳毒素敏感的方式对钙诱导的磷脂酶A2进行允许性刺激:钙信号传导中的一种新的“串扰”机制。
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Separate P2T and P2U purinergic receptors with similar second messenger signaling pathways in UMR-106 osteoblasts.
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Modeling Interactions among Individual P2 Receptors to Explain Complex Response Patterns over a Wide Range of ATP Concentrations.模拟个体P2受体之间的相互作用以解释在广泛ATP浓度范围内的复杂反应模式。
Front Physiol. 2016 Jul 13;7:294. doi: 10.3389/fphys.2016.00294. eCollection 2016.
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Purinergic receptors and nucleotide processing ectoenzymes: Their roles in regulating mesenchymal stem cell functions.嘌呤能受体与核苷酸加工外切酶:它们在调节间充质干细胞功能中的作用。
World J Stem Cells. 2014 Apr 26;6(2):153-62. doi: 10.4252/wjsc.v6.i2.153.
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Purinergic signalling in the musculoskeletal system.嘌呤能信号在肌肉骨骼系统中的作用。
Purinergic Signal. 2013 Dec;9(4):541-72. doi: 10.1007/s11302-013-9381-4. Epub 2013 Aug 14.
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Extracellular ATP released by osteoblasts is a key local inhibitor of bone mineralisation.成骨细胞释放的细胞外 ATP 是局部抑制骨矿化的关键物质。
PLoS One. 2013 Jul 9;8(7):e69057. doi: 10.1371/journal.pone.0069057. Print 2013.
8
Receptor-independent effects of 2'(3')-O-(4-benzoylbenzoyl)ATP triethylammonium salt on cytosolic pH.2'(3')-O-(4-苯甲酰苯甲酰基)ATP 三乙铵盐对细胞浆 pH 的受体非依赖性作用。
Purinergic Signal. 2013 Dec;9(4):687-93. doi: 10.1007/s11302-013-9365-4. Epub 2013 May 22.
9
Adenosine and bone metabolism.腺苷与骨代谢。
Trends Endocrinol Metab. 2013 Jun;24(6):290-300. doi: 10.1016/j.tem.2013.02.001. Epub 2013 Mar 14.
10
An emerging role for adenosine and its receptors in bone homeostasis.腺苷及其受体在骨稳态中的新作用。
Front Endocrinol (Lausanne). 2012 Sep 18;3:113. doi: 10.3389/fendo.2012.00113. eCollection 2012.
在UMR-106成骨细胞中分离具有相似第二信使信号通路的P2T和P2U嘌呤能受体。
J Pharmacol Exp Ther. 1994 Jun;269(3):1049-61.
4
Mitogenic effects of ATP on vascular smooth muscle cells vs. other growth factors and sympathetic cotransmitters.ATP对血管平滑肌细胞的促有丝分裂作用与其他生长因子及交感神经共递质的比较。
Am J Physiol. 1993 Oct;265(4 Pt 2):H1089-97. doi: 10.1152/ajpheart.1993.265.4.H1089.
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Fracture healing perspectives.骨折愈合的观点。
Clin Orthop Relat Res. 1985 Nov(200):100-13.
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Extracellular ATP: effects, sources and fate.细胞外ATP:作用、来源及去向
Biochem J. 1986 Jan 15;233(2):309-19. doi: 10.1042/bj2330309.
7
Is there a basis for distinguishing two types of P2-purinoceptor?是否有依据区分两种类型的P2嘌呤受体?
Gen Pharmacol. 1985;16(5):433-40. doi: 10.1016/0306-3623(85)90001-1.
8
Prostaglandin E1 and F2 alpha stimulate differentiation and proliferation, respectively, of clonal osteoblastic MC3T3-E1 cells by different second messengers in vitro.前列腺素E1和F2α在体外通过不同的第二信使分别刺激克隆性成骨细胞MC3T3-E1细胞的分化和增殖。
Endocrinology. 1987 Dec;121(6):1966-74. doi: 10.1210/endo-121-6-1966.
9
Extracellular ATP is a mitogen for 3T3, 3T6, and A431 cells and acts synergistically with other growth factors.细胞外ATP是3T3、3T6和A431细胞的促有丝分裂原,并与其他生长因子协同作用。
Proc Natl Acad Sci U S A. 1989 Oct;86(20):7904-8. doi: 10.1073/pnas.86.20.7904.
10
Extracellular ATP induces the release of calcium from intracellular stores without the activation of protein kinase C in Swiss 3T6 mouse fibroblasts.细胞外ATP可诱导瑞士3T6小鼠成纤维细胞从细胞内储存库释放钙,而无需激活蛋白激酶C。
Proc Natl Acad Sci U S A. 1989 Jun;86(12):4530-4. doi: 10.1073/pnas.86.12.4530.