信号通路在膝骨关节炎实验研究中的进展

doi:10.3969/j.issn.2095-4344.2016.02.020

中国组织工程研究 ›› 2016, Vol. 20 ›› Issue (2): 267-272.doi: 10.3969/j.issn.2095-4344.2016.02.020

• 组织构建综述 tissue construction review • 上一篇下一篇

信号通路在膝骨关节炎实验研究中的进展

王华敏^1，2，宓轶群^1，2，刚嘉鸿²

¹上海中医药大学研究生院，上海市 201203；²上海交通大学附属第六人民医院针推伤科，上海市 200233

收稿日期:2015-11-03 出版日期:2016-01-08 发布日期:2016-01-08
通讯作者: 宓轶群，主任医师，硕士生导师，上海中医药大学研究生院，上海市 201203；上海交通大学附属第六人民医院针推伤科，上海市 200233
作者简介:王华敏，男，1988年生，山西省孝义市人，汉族，上海中医药大学在读硕士。
基金资助:
课题由上海市卫生和计划生育委员会、上海市中医药发展办公室上海市中医药三年行动计划项目(zy3-pcpy- 3-1018)资助

Experimental progress of signal transduction pathways in knee osteoarthritis

Wang Hua-min^{1, 2}, Mi Yi-qun^{1, 2}, Gang Jia-hong²

¹Graduate School of Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; ²Department of Acupuncture & Moxibustion Tuina Traumatology, the Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University, Shanghai 200233, China

Received:2015-11-03 Online:2016-01-08 Published:2016-01-08
Contact: Mi Yi-qun, Chief physician, Master’s supervisor, Graduate School of Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Department of Acupuncture & Moxibustion Tuina Traumatology, the Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University, Shanghai 200233, China
About author:Wang Hua-min, Studying for master’s degree, Graduate School of Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Department of Acupuncture & Moxibustion Tuina Traumatology, the Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University, Shanghai 200233, China
Supported by:
the Three-Year Action Plan Project of Shanghai Traditional Chinese Medicine of Shanghai Municipal Commission of Health and Family Planning and the Office of Chinese Medicine Development, No. zy3-pcpy-3-1018

摘要/Abstract

摘要：

文章快速阅读：

文题释义：

信号通路：当细胞里要发生某种反应时，信号从细胞外到细胞内传递了一种信息，细胞要根据这种信息来做出反应的现象，叫做信号通路，指能将细胞外的分子信号经细胞膜传入细胞内发挥效应的一系列酶促反应通路。这些细胞外的分子信号(称为配体，ligand)包括激素、生长因子、细胞因子、神经递质以及其它小分子化合物等。

膝骨关节炎：一般指膝关节炎。膝关节炎是一种以退行性病理改变为基础的疾患。多患于中老年人群，其症状多表现为膝盖红肿痛、上下楼梯痛、坐起立行时膝部酸痛不适等。也会有患者表现肿胀、弹响、积液等，如不及时治疗，则会引起关节畸形，残废。在膝关节部位还常患有膝关节滑膜炎、韧带损伤、半月板损伤、膝关节游离体、腘窝囊肿、髌骨软化、鹅足滑囊炎、膝内/外翻等关节疾病。

背景：研究表明信号通路在膝骨关节炎发病过程中起着重要的作用。

目的：详细阐述信号通路在膝骨关节炎的实验研究进展。

方法：查阅PubMed、CNKI、维普、万方等相关数据库，查找关于膝骨关节炎的信号通路实验研究的相关文献，对资料进行筛选，排除重复研究和关联性较小的文献，保留与膝骨关节炎信号通路关联性较大的文献。

结果与结论：共纳入51篇符合标准的文献，包括中文文献20篇，英文文献31篇。经分析得出：与膝关节骨性关节炎相关的信号通路主要集中在软骨细胞的增殖和软骨细胞的凋亡两个方面。与软骨细胞增殖有关的信号通路主要有Notch信号通路和Wnt信号通路；与软骨细胞凋亡的信号通路有基质细胞衍生因子1/趋化因子受体4信号通路、TLR4信号通路和MAPKs信号通路；Hippo-YAP信号通路与ERK1/2信号通路具有双重调节软骨细胞增殖和凋亡的作用。

中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程

ORCID: 0000-0002-1977-3631宓轶群)(

关键词: 组织构建, 软骨组织工程, 信号通路, 骨关节炎, 膝, 软骨细胞, 综述

Abstract:

BACKGROUND: Studies have shown that signaling pathway plays an important role in the pathogenesis of knee osteoarthritis.
OBJECTIVE: To elaborate the experimental progress of signal transduction pathway in knee osteoarthritis
METHODS: A computer-based retrieval of PubMed, CNKI, VIP and Wanfang databases was performed to find the relevant literatures concerning experimental studies of signaling pathway in knee osteoarthritis. All data were primarily screened to exclude repeated and irrelevant articles. Articles about association between knee osteoarthritis and signal pathway were included.

RESULTS AND CONCLUSION: A total of 51 articles were collected, including 20 in Chinese and 31 in English. It is concluded that the signal transduction pathway related to knee osteoarthritis is mainly concentrated in the two aspects: the proliferation of chondrocytes and the apoptosis of chondrocytes. The signal transduction pathways related to the proliferation of chondrocytes mainly include Notch signaling pathway and Wnt signaling pathway. SDF-1/CXCR4 signaling pathway, TLR4 signaling pathway, and MAPKs signaling pathway are associated with apoptosis in chondrocytes. Hippo-YAP signaling pathway and ERK1/2 signaling pathway have a double role in the regulation of proliferation and apoptosis of chondrocytes.

中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程

王华敏，宓轶群，刚嘉鸿. 信号通路在膝骨关节炎实验研究中的进展[J]. 中国组织工程研究, 2016, 20(2): 267-272.

Wang Hua-min, Mi Yi-qun, Gang Jia-hong. Experimental progress of signal transduction pathways in knee osteoarthritis[J]. Chinese Journal of Tissue Engineering Research, 2016, 20(2): 267-272.

参考文献

[1] Ghosh P,Smith M.Osteoarthritis, genetic and molecular mechanisms. Biogerontology.2002;3(1-2): 85-88.

[2] Nam Y, Aster JC, Blacklow SC. Notch signaling as a therapeutic target. Current Opinion Chem Biology.2002; 6(4): 501-509.

[3] Williams R, Nelson L, Dowthwaite GP, et al. Notch receptor and Notch ligand expression in developing avian cartilage. J Anat. 2009 ;215(2):159-169.

[4] Ustunel I, Ozenci AM, Sahin Z, et al. The immunohistochemical localization of notch receptors and ligands in human articular cartilage, chondroprogenitor culture and ultrastructural characteristics of these progenitor cells. Acta histochemica. 2008;110(5): 397-407.

[5] Grogan SP, Miyaki S, Asahara H, et al. Mesenchymal progenitor cell markers in human articular cartilage: normal distribution and changes in osteoarthritis. Arthri Res Therapy. 2009;11(3): R85.

[6] Kandachar V, Roegiers F. Endocytosis and control of Notch signaling. Current opinion in cell biology;2012;24(4): 534-540.

[7] Karlsson C, Brantsing C, Svensson T, et al. Differentiation of human mesenchymal stem cells and articular chondrocytes: Analysis of chondrogenic potential and expression pattern of differentiation-related transcription factors. J Orthop Res. 2007; 25(2):152-163.

[8] Hosaka Y, Saito T, Sugita S, et al. Notch signaling in chondrocytes modulates endochondral ossification and osteoarthritis development. Proc Natl Acad Sci USA. 2013;110(5):1875-1880.

[9] Karlsson C, Brantsing C, Egell S, et al. Notch1, Jagged1, and HES5 are abundantly expressed in osteoarthritis. Cells Tissues Organs.2008;188(3): 287-298.

[10] Meier-Stiegen F, Schwanbeck R, Bernoth K, et al. Activated Notch1 target genes during embryonic cell differentiation depend on the cellular context and include lineage determinants and inhibitors. PLoS One.2010;5(7): e11481.

[11] Watanabe N, Tezuka Y, Matsuno K, et al. Suppression of differentiation and proliferation of early chondrogenic cells by Notch. J Bone Miner Metab. 2003;21(6):344-352.

[12] Fujimaki R, Toyama Y, Hozumi N, et al.Involvement of Notch signaling in initiation of prechondrogenic condensation and nodule formation in limb bud micromass cultures. J Bone Miner Metab. 2006;24(3):191-198.

[13] Bergwitz C, Wendlandt T, Kispert A, et al. Wnts differentially regulate colony growth and differentiation of chondrogenic rat calvaria cells. Biochim Biophys Acta. 2001;1538(2-3): 129-140.

[14] Weng X, Lin P, Liu F, et al. Achyranthes bidentata polysaccharides activate the Wnt/β-catenin signaling pathway to promote chondrocyte proliferation. Int J Mol Med. 2014;3 4(4): 1045-1050.

[15] Li X, Peng J, Wu M, et al. BMP2 promotes chondrocyte proliferation via the Wnt/β-catenin signaling pathway. Molecular medicine reports.2011;4(4): 621-626.

[16] Wei F, Moore DC, Li Y, et al. Attenuation of osteoarthritis via blockade of the SDF-1/CXCR4 signaling pathway. Arthritis Res Ther.2012;14(4): R177.

[17] 李彦林,王国梁,曹斌,等.AMD3100体外阻断基质细胞衍生因子1/趋化因子受体4信号通路对人关节软骨细胞分泌基质金属蛋白酶3、9、13水平的影响[J]. 中国修复重建外科杂志, 2012, 26(6):652-656.

[18] Kim HA, Cho ML, Choi HY, et al. The catabolic pathway mediated by Toll-like receptors in human osteoarthritic chondrocytes. Arthritis & Rheumatism.2006;54(7): 2152-2163.

[19] 钱臣,卞晓星. Toll样受体4表达与膝骨关节炎软骨细胞凋亡的关系[J].江苏大学学报:医学版,2015,25(2):128-132

[20] Kawai T, Akira S. The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nature Immunology.2010;11(5): 373-384.

[21] 王永福,林剑,詹宏刚. CD14/TLR-4-NF-κB信号通路参与骨关节炎发病机制的研究[J]. 实用骨科杂志, 2013, 19(6): 528-530.

[22] 陈建勇,王聪,王娟,等. MAPK信号通路研究进展[J].中国医药科学, 2011, 1(8): 32-34.

[23] Yoon HS, Kim HA. Prologation of c-Jun N-terminal kinase is associated with cell death induced by tumor necrosis factor alpha in human chondrocytes. J Korean Med Sci. 2004; 19(4):567-573.

[24] 张频捷, 朱立新,耿小平. p38 MAPK信号传导通路及其抑制剂的研究现状[J]. 安徽医药, 2010, 14(5): 596-598.

[25] Kühn K, Shikhman A R, Lotz M. Role of nitric oxide, reactive oxygen species, and p38 MAP kinase in the regulation of human chondrocyte apoptosis. J Cell Physiol. 2003; 197(3): 379-387.

[26] 秦泗通,蒋青,黄际河,等.p38 丝裂原活化蛋白激酶抑制剂对大鼠骨关节炎软骨细胞凋亡的影响[J].山东医药, 2008, 48(6): 6-8.

[27] 王红林,王治伦,吴劲,等. p38 MAPK 信号转导通路参与NO诱导兔关节软骨细胞凋亡[J].中国地方病防治杂志, 2007, 21(6): 332-335.

[28] 林飞太,林煜,张怡元,等.独活寄生汤含药血清对兔退变软骨细胞“caveolin-p38MAPK”信号通路调控作用的影响[J].风湿病与关节炎, 2015, 4(4): 5-9.

[29] Yu FX, Mo JS, Guan KL. Upstream regulators of the Hippo pathway. Cell cycle. 2012; 11(22): 4097-4098.

[30] Tremblay AM, Camargo FD. Hippo signaling in mammalian stem cells[C].Seminars in cell & developmental biology. Academic Press. 2012;23(7): 818-826.

[31] Zhong W, Li Y, Li L, et al. YAP-mediated regulation of the chondrogenic phenotype in response to matrix elasticity. J Mol Histol. 2013;44(5):587-595.

[32] Karystinou A, Roelofs AJ, Neve A, et al. Yes-associated protein (YAP) is a negative regulator of chondrogenesis in mesenchymal stem cells. Arthritis Research & Therapy.2015; 17(1):147.

[33] 何正言,梅浩.Hippo-YAP信号通路在人膝骨性关节炎中表达的意义[J].中国实用医药.2013,8(15):24-25.

[34] Bobick BE, Kulyk WM. MEK-ERK signaling plays diverse roles in the regulation of facial chondrogenesis. Exp Cell Res. 2006 ;312(7):1079-1092.

[35] 高世超,殷海波刘宏潇,等. MAPK信号通路在骨关节炎发病机制中的研究进展[J].中国骨伤, 2014,27 (5): 441-444.

[36] Pelletier JP, Fernandes JC, Brunet J, et al. In vivo selective inhibition of mitogen-activated protein kinase kinase 1/2 in rabbit experimental osteoarthritis is associated with a reduction in the development of structural changes. Arthritis Rheum. 2003;48(6):1582-1593.

[37] Boileau C, Martel-Pelletier J, Brunet J, et al. PD-0200347, an α2δ ligand of the voltage gated calcium channel, inhibits in vivo activation of the Erk1/2 pathway in osteoarthritic chondrocytes: a PKCα dependent effect. Ann Rheum Dis. 2006;65(5):573-580.

[38] Prasadam I, Friis T, Shi W, et al. Osteoarthritic cartilage chondrocytes alter subchondral bone osteoblast differentiation via MAPK signalling pathway involving ERK1/2. Bone.2010; 46(1): 226-235

[39] 任科伟,范卫民,姜雪峰,等.周期性机械应力通过激活 EGFR-ERKl/2信号通路促进大鼠软骨细胞增殖和细胞外基质合成[J]. 江苏医药, 2013, 39(21): 2526-2528.

[40] 史冰楠. 淫羊藿甙对关节软骨细胞增殖,分泌及MAPKs通路的影响[D]. 华中农业大学,2013.

[41] Schulze-Tanzil G, Mobasheri A, de Souza P, et al. Loss of chondrogenic potential in dedifferentiated chondrocytes correlates with deficient Shc–Erk interaction and apoptosis. Osteoarthritis Cartilage. 2004;12(6):448-458.

[42] 罗玉明,郑维篷,魏合伟.骨关节炎与细胞因子TNF-α, IL-6关系的研究进展[J].现代诊断与治疗,2013 (2): 326-327.

[43] 龚元勋,马骏,王述菊,等.细胞外调节蛋白激酶与肿瘤坏死因子α的研究进展[J].内蒙古中医药, 2014, 33(9): 138-138.

[44] 周小莉,李荣亨.复元胶囊对软骨细胞凋亡细胞外信号调节蛋白激酶1/2信号通路的作用研究[J]. 中国老年学杂志, 2008, 28(4): 329-331

[45] 付小霞. 降钙素对IL-1β体外诱导培养的大鼠软骨细胞MAPKs 信号通路影响的初步研究[D]. 河北联合大学, 2011.

[46] Tat SK, Pelletier JP, Velasco CR, et al. New perspective in osteoarthritis: the OPG and RANKL system as a potential therapeutic target?. The Keio journal of medicine, 2009, 58(1): 29-40.

[47] 李荣亨,李强.OPG-RANK-RANKL细胞信号通路在骨关节炎中的研究进展[C].全国第十一届中西医结合风湿病学术会议论文汇编.2013.

[48] 李锦,罗明秀,王加丽,等.整合素-肌动蛋白信号转导通路与骨关节炎[J].国外医学,2011,32(3):215-219.

[49] Finnson K W, Chi Y, Bou-Gharios G, et al. TGF-β signaling in cartilage homeostasis and osteoarthritis. Front Biosci (Schol Ed).2012;4: 251-268.

[50] 秦庆华,姚咏明.转化生长因子β信号通路研究进展[J]. 医学研究杂志, 2012, 41(10): 5-9.

[51] 张荣凯,陈琰,张颂阳,等.转化生长因子-β通路在早期创伤性骨性关节炎软骨下骨的动态变化[J].中华创伤骨科杂志,2013,15(2): 132-137.

信号通路在膝骨关节炎实验研究中的进展

Experimental progress of signal transduction pathways in knee osteoarthritis

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