信号通路在骨性关节炎发病中的作用

李龙滕; 李彦林; 王坤; 肖渝; 闫祥甲

信号通路在骨性关节炎发病中的作用

昆明医科大学第一附属医院运动医学科

基金项目:

基金：国家自然科学基金资助项目(81460340); 云南省创新团队基金资助项目(2014HC018); 云南省医疗卫生单位内设研究机构基金资助项目(2014NS161);

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出版历程
- 收稿日期: 2016-11-14

The Role of Singal Pathways in Osteoarthritis

Funds:

基金：国家自然科学基金资助项目(81460340); 云南省创新团队基金资助项目(2014HC018); 云南省医疗卫生单位内设研究机构基金资助项目(2014NS161);

摘要

摘要: 骨性关节炎(osteoarthritis,OA)是一种多种原因导致关节软骨退变和继发性骨质增生为主的慢性滑膜关节疾病,其发病机制复杂多样,尚不完全清楚,目前对OA采取的治疗方法较多,但效果均不明显,只能短期缓解症状、改善关节功能,不能阻止OA的病理进程,更不可能逆转关节软骨的退变.目前国内外对信号通路与骨性关节炎的研究成为一个热点,大量研究证实骨性关节炎的发生、发展与SDF-1/CXCR4、MAPK、Wnt、OPG/RANKL/RANK等信号通路均有关系,但没有任何一条信号通路能完全解释骨性关节炎的发病机制,也不能靠阻断单一信号通路而达到治疗OA的效果,故而针对治疗OA发病机制的研究和新型药物的研制成为了目前研究的热点.就目前国内外关于信号通路在骨性关节炎发展中的作用进行综述,希望对骨性关节炎的研究和治疗提供理论依据.
- 骨性关节炎 /
- 信号通路 /
- SDF-1 /
- CXCR4 /
- MAPK
Abstract: Osteoarthritis is the chronic articulatio-synovialis disease which features as cartilage degenerate and secondary osteoproliferation. Current pharmacologic therapy is largely ineffective at altering progression of the disease because the varitious mechanisms for OA remain elusive. The various therapeutic method of OA are not obvious,just relieve symptom or improve the function of joints in short.It is imposbille to stop pathological process of OA, not to mention reverse the degeneration of cartilage.It is a hot study between singal pathway and osteoarthritis,mroe and more researches confirm that the singal pathway of SDF-1/CXCR4,MAPK,Wnt,OPG/RANKL/RANK etc have close association with the generation and progress of OA.However, none of the singgal pathways can completely explan the mechanism of OA,or cure OA by block any singal pathway.So it is hotop to study mechanisms of OA and mew drugs.This rewiew focuses on singal pathway to OA in internation, hope to support theoretical foundation for study and therapy of OA
- Osteoarthritis /
- Signal pathway /
- SDF-1 /
- CXCR4 /
- MAPK

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参考文献(36)

[1]	[1]HE W,WANG M,WANG Y,et al.Plasma and synovial fluid CXCL12 levels are correlated with disease severity in patients with knee osteoarthritis[J].The Journal of Arthroplasty,2016,31(2):373-377.
[2]	[2]KAROUZAKIS E,RENGEL Y,JUNGEL A,et al.DNA methylation regulates the expression of CXCL12 in rheumatoid arthritis synovial fibroblasts[J].Genes and Immunity,2011,12(8):643-652.
[3]	[3]WEI L,KANBE K,LEE M,et al.Stimulation of chondrocyte hypertrophy by chemokine stromal cell-derived factor 1 in the chondro-osseous junction during endochondral bone formation[J].Developmental Biology,2010,341(1):236-245.
[4]	[4]JONES S W,BROCKBANK S M,MOBBS M L,et al.The orphan G-protein coupled receptor RDC1:Evidence for a role in chondrocyte hypertrophy and articular cartilage matrix turnover[J].Osteoarthritis&Cartilage,2006,14(6):597-608.
[5]	[5]WEI F,MOORE D C,WEI L,et al.Attenuation of osteoarthritis via blockade of the SDF-1/CXCR4 signaling pathway[J].Arthritis Research&Therapy,2012,14(4):1-11.
[6]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.
[7]王坤,赵沣凯,李彦林,等.T140体内靶向阻断SDF-1/CXCR4信号通路对SDF-1及MMPs的影响[J].实用医学杂志,2015,31(19):3133-3136.
[8]马珂,李晓林,李彦林,等.T140体外阻断SDF-1/CXCR4信号通路对人关节软骨细胞分泌MMP-3、MMP-9和MMP-13水平的影响[J].中国运动医学杂志,2013,32(9):807-823.
[9]	[9]CHEN H T,TSOU H K,HSU C J,et al.Stromal cell-derived factor-1/CXCR4 promotes IL-6 production in human synovial fibroblasts[J].Journal of Cellular Biochemistry,2011,112(4):1219-1227.
[10]	[10]VILLALVILLA A,GOMEZ R,ROMAN-BLAS J A,et al.SDF-1 signaling:a promising target in rheumatic diseases[J].Expert Opinion on Therapeutic Targets,2014,18(9):1077-1087.
[11]	[11]PRINCEN K,HATSE S,VERMEIRE K,et al.Evaluation of SDF-1/CXCR4-induced Ca2+signaling by fluorometric imaging plate reader(FLIPR)and flow cytometry[J].Cytometry Part A,2003,51(1):35-45.
[12]	[12]WANG X Y,CHEN Y,TANG X J,et al.AMD3100Attenuates matrix metalloprotease-3 and-9 expressions and prevents cartilage degradation in a monosodium Iodo-acetate-induced rat model of temporomandibular osteoarthritis[J].J Oral Maxillofac Surg,2016,74(5):1-13.
[13]	[13]KONG D,ZHENG T,ZHANG M,et al.Static mechanical stress induces apoptosis in rat endplate chondrocytes through MAPK and mitochondria-dependent caspase activation signaling pathways[J].Plo S One,2013,8(7):1-10.
[14]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.
[15]	[15]ROSS S,CHEN T,YU V,et al.High-content screening analysis of the p38 pathway:Profiling of structurally related p38alpha kinase inhibitors using cell-based assays[J].Assay and Drug Development Technologies,2006,4(4):397-409.
[16]	[16]LIM H,KIM H P.Matrix metalloproteinase-13 expression in IL-1beta-treated chondrocytes by activation of the p38MAPK/c-Fos/AP-1 and JAK/STAT pathways[J].Archives of Pharmacal Research,2011,34(1):109-117.
[17]	[17]KUMAR S,VOTTA B J,RIEMAN D J,et al.IL-1-and TNF-induced bone resorption is mediated by p38 mitogen activated protein kinase[J].Journal of Cellular Physiology,2001,187(3):294-303.
[18]	[18]CHEN WP,XIONG Y,HU P F,et al.Baicalein inhibits MMPs expression via a MAPK-dependent mechanism in chondrocytes[J].Cellular Physiology and Biochemistry:International Journal of Experimental Cellular Physiology,Biochemistry,And Pharmacology,2015,36(1):325-333.
[19]	[19]FANJUL-FERNANDEZ M,FOLGUERAS A R,CABRERA S,et al.Matrix metalloproteinases:evolution,gene regulation and functional analysis in mouse models[J].Biochimica Etbiophysica Acta,2010,1803(1):3-19.
[20]	[20]ROSKOSKI R,J R.ERK1/2 MAP kinases:structure,function,and regulation[J].Pharmacological Research,2012,66(2):105-143.
[21]	[21]ZHANG Y,PIZZUTE T,PEI M.A review of crosstalk between MAPK and Wnt signals and its impact on cartilage regeneration[J].Cell and Tissue Research,2014,358(3):633-649.
[22]	[22]ZHU S,LIU H,WU Y,et al.Wnt and Rho GTPase signaling in osteoarthritis development and intervention:implications for diagnosis and therapy[J].Arthritis Research&Therapy,2013,15(4):217.
[23]代金龙,代紫玉,尹超,等.β-连环蛋白与与膝骨关节炎相关性研究[J].昆明医科大学学报,2015,36(12):120-122.
[24]	[24]YUASA T,OTANI T,KOIKE T,et al.Wnt/beta-catenin signaling stimulates matrix catabolic genes and activity in articular chondrocytes:its possible role in joint degeneration[J].Laboratory Investigation;A Journal of Technical Methods and Pathology,2008,88(3):264-274.
[25]	[25]DIARRA D,STOLINA M,POLZER K,et al.Dickkopf-1is a master regulator of joint remodeling[J].Nature Medicine,2007,13(2):156-163.
[26]宋朋飞阚卫兵,赵婧,等.正常人滑膜细胞Wnt/β-catenin信号通路激活后对MMP-2、MMP-7和MMP-9的调控作用[J].中国现代医学杂志,2014,24(5):22-27.
[27]	[27]WENG L H,WANG C J,KO J Y,et al.Inflammation induction of Dickkopf-1 mediates chondrocyte apoptosis in osteoarthritic joint[J].Osteoarthritis and Cartilage/OARS,Osteoarthritis Research Society,2009,17(7):933-943.
[28]	[28]VAN DEN BOSCH M H,BLOM A B,SLOETJES A W,et al.Induction of canonical wnt signaling by synovial overexpression of selected wnts leads to protease activity and early osteoarthritis-like cartilage damage[J].The American Journal of Pathology,2015,185(7):1970-1980.
[29]岳振双,辛大伟,戚记伟,等.Wnt信号通路与骨性关节炎关系的研究进展[J].中医正骨,2010,22(10):32-35.
[30]	[30]PILICHOU A,PAPASSOTIRIOU I,MICHALAKAKOU K,et al.High levels of synovial fluid osteoprotegerin(OPG)and increased serum ratio of receptor activator of nuclear factor-kappa B ligand(RANKL)to OPG correlate with disease severity in patients with primary knee osteoarthritis[J].Clinical Biochemistry,2008,41(9):746-749.
[31]	[31]LOGAR DB,KOMADINA R,PREZELJ J,et al.Expression of bone resorption genes in osteoarthritis and in osteoporosis[J].Journal of Bone and Mineral Metabolism,2007,25(4):219-225.
[32]	[32]UPTON AR,HOLDING CA,DHARMAPATNI AA,et al.The expression of RANKL and OPG in the various grades of osteoarthritic cartilage[J].Rheumatology International,2012,32(2):535-540.
[33]	[33]MORENO-RUBIO J,HERRERO-BEAUMONT G,TARDIO L,et al.Nonsteroidal antiinflammatory drugs and prostaglandin E(2)modulate the synthesis of osteoprotegerin and RANKL in the cartilage of patients with severe knee osteoarthritis[J].Arthritis and Rheumatism,2010,62(2):478-488.
[34]	[34]CHEN L X,LIN L,WANG H J,et al.Suppression of early experimental osteoarthritis by in vivo delivery of the adenoviral vector-mediated NF-kappa Bp65-specific si RNA[J].Osteoarthritis and Cartilage/OARS,Osteoarthritis Research Society,2008,16(2):174-184.
[35]谢少利,幸天勇,邓世山.泛素蛋白连接酶E3介导的EMT在在肿瘤浸润与转移中的作用[J].川北医学院学报,2015,5(42):732-737.
[36]	[36]HOSAKA Y,SAITO T,SUGITA S,et al.Notch signaling in chondrocytes modulates endochondral ossification and osteoarthritis development[J].Proceedings of the National Academy of Sciences of the United States of America,2013,110(5):1875-1880.

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