基于生物信息学方法鉴别骨关节炎自噬的关键基因和途径

Abstract
Figure/Table
References (29)
Related Citation (15)

Download: PDF (1191 KB) HTML (1 KB)
Export: BibTeX | EndNote (RIS)

Abstract Objective To explore the potential role of autophagy related genes in osteoarthritis (OA) by bioinformatics methods. Methods Using the GEO DataSets retrieval window of the GEO database with the keyword “Osteoarthritis”, the data disclosure date was limited to January 1st, 2010 to January 1st, 2020. The gene microarray dataset (GSE55457) was screened, and the differentially expressed genes (DEGs) were obtained from GSE55457 after correction. Then, the autophagy related genes obtained from GeneCards were used to intersection with DEGs, and the intersection genes were performed by GO and KEGG enrichment analysis and the proteinprotein interaction network was mapped. Finally, the key modules were obtained and the key genes of Hub were screened by KEGG enrichment analysis. Results A total of 203 DEGs and 5786 autophagy genes were obtained, and 65 genes were obtained from the intersection of the two, which were enriched in 279 GO entries and 44 KEGG entries. The genes of important modules were mainly involved in MAPK, JAK-STAT, and PI3K-Akt signaling pathways, and the key genes were VEGFA, JUN, CTNNB1, MYC, NR4A1, MAP2K7, and DUSP1. Conclusion The genes VEGFA, JUN, and CTNNB1 regulate the autophagy response through the main pathways of MAPK, JAK-STAT, and PI3K-Akt, and affect the occurrence and development of OA.

Key words： Osteoarthritis Autophagy Signaling pathways Genes Bioinformatics

	Service

	E-mail this article
	Add to my bookshelf
	Add to citation manager
	E-mail Alert
	RSS
	Articles by authors
	YUAN Changshen1 RONG Weiming2 LI Zhe2 GUAN Yanbing2 MEI Qijie1 DUAN Kan1

Cite this article:

YUAN Changshen1 RONG Weiming2 LI Zhe2 GUAN Yanbing2 MEI Qijie1 DUAN Kan1. Identification of key genes and pathways for autophagy in osteoarthritis based on bioinformatics methods[J]. 中国医药导报, 2021, 18(25): 9-13.

URL:

https://www.yiyaodaobao.com.cn/EN/ OR https://www.yiyaodaobao.com.cn/EN/Y2021/V18/I25/9

[1] Taylor N. Nonsurgical Management of Osteoarthritis Knee Pain in the Older Adult：An Update [J]. Rheum Dis Clin North Am，2018，44（3）：513-524.
[2] Kiadaliri AA，Lohmander LS，Moradi-Lakeh M，et al. High and rising burden of hip and knee osteoarthritis in the Nordic region，1990-2015 [J]. Acta Orthop，2018，89（2）：177-183.
[3] Caramés B，Taniguchi N，Otsuki S，et al. Autophagy is a protective mechanism in normal cartilage，and its aging-related loss is linked with cell death and osteoarthritis [J]. Arthritis Rheum，2010，62（3）：791-801.
[4] Rockel JS，Kapoor M. Autophagy：controlling cell fate in rheumatic diseases [J]. Nat Rev Rheumatol，2016，12（9）：517-531.
[5] Lotz MK，Caramés B. Autophagy and cartilage homeostasis mechanisms in joint health，aging and OA [J]. Nat Rev Rheumatol，2011，7（10）：579-587.
[6] Fernandes JC，Martel-Pelletier J，Pelletier JP. The role of cytokines in osteoarthritis pathophy-Siology [J]. Biorheology，2002，39（1/2）：237-246.
[7] Chen Y，Shou K，Gong C，et al. Anti-Inflammatory Effect of Geniposide on Osteoarthritis by Suppressing the Activation of p38 MAPK Signaling Pathway [J]. Biomed Res Int，2018，2018：8384576.
[8] Shi J，Zhang C，Yi Z，et al. Explore the variation of MMP3，JNK，p38 MAPKs，and autophagy at the early stage of osteoarthritis [J]. IUBMB Life，2016，68（4）：293-302.
[9] Morris R，Kershaw NJ，Babon JJ. The molecular details of cytokine signaling via the JAK/STAT pathway [J]. Protein Sci，2018，27（12）：1984-2009.
[10] Jonchère B，Bélanger A，Guette C，et al. STAT3 as a new autophagy regulator [J]. JAKSTAT，2013，2（3）：e24353.
[11] Zhang LJ，Ni SZ，Zhou XL，et al. Hemorrhagic Shock Sensitized the Diaphragm to Ventilator-Induced Dysfunction through the Activation of IL-6/JAK/STAT Signaling-Mediated Autophagy in Rats [J]. Mediators Inflamm，2019，2019：3738409.
[12] Chen H，Wu G，Sun Q，et al. Hyperbaric oxygen protects mandibular condylar chondrocytes from interleukin-1β-induced apoptosis via the PI3K/AKT signaling pathway [J]. Am J Transl Res，2016，8（11）：5108-5117.
[13] Xu J，Yi Y，Li L，et al. Osteopontin induces vascular endothelial growth factor expression in articular cartilage through PI3K/AKT and ERK1/2 signaling [J]. Mol Med Rep，2015，12（3）：4708-4712.
[14] Xue JF，Shi ZM，Zou J，et al. Inhibition of PI3K/AKT/mTOR signaling pathway promotes autophagy of articular chondrocytes and attenuates inflammatory response in rats with osteoarthritis [J]. Biomed Pharmacother，2017， 89：1252-1261.
[15] 梁治权，顾文飞，廖军.清热解毒通络汤联合塞来昔布对骨关节炎患者血清相关炎性因子水平的影响[J].中国医药，2018，13（3）：433-436.
[16] 郭静，张娜，秦丽娟，等.膝骨关节炎患者中IL-18、VEGF和NF-κB的表达及意义[J].实用医学杂志，2013，29（18）：3024-3026.
[17] Liang L，Hui K，Hu C，et al. Autophagy inhibition potentiates the anti-angiogenic property of multikinase inhibitor anlotinib through JAK2/STAT3/VEGFA signaling in non-small cell lung cancer cells [J]. J Exp Clin Cancer Res，2019，38（1）：71.
[18] 叶臻，李民，郭逸尔.消痹方对兔膝骨性关节炎软骨下骨c-jun mRNA影响[J].辽宁中医药大学学报，2016， 18（12）：32-34.
[19] Li Z，Chen S，Chen S，et al. Moderate activation of Wnt/β-catenin signaling promotes the survival of rat nucleus pulposus cells via regulating apoptosis，autophagy，and senescence [J]. J Cell Biochem，2019，120（8）：12519-12533.
[20] Wang J，Wang Y，Zhang H，et al. Forkhead box C1 promotes the pathology of osteoarthritis by upregulating β-catenin in synovial fibroblasts [J]. FEBS J，2019，287（14）：3065-3087. DOI：10.1111/febs.15178.
[21] 刘亦斌，李小军，刘强，等.Wnt/β-catenin信号通路与自噬在骨关节炎软骨细胞中的相互作用[J].宁夏医科大学学报，2019（4）：325-331.
[22] Schick M，Habringer S，Nilsson JA，et al. Pathogenesis and therapeutic targeting of aberrant MYC expression in haematological cancers [J]. Br J Haematol，2017，179（5）：724-738.
[23] Yatsugi N，Tsukazaki T，Osaki M，et al. Apoptosis of articular chondrocytes in rheumatoid arthritis and osteoarthritis：correlation of apoptosis with degree of cartilage destruction and expression of apoptosis-related proteins of p53 and c-myc [J]. J Orthop Sci，2000，5（2）：150-156.
[24] Kumar P，Yao LJ，Saidin S，et al. Molecular mechanisms of autophagic memory in pathogenic T cells in human arthritis [J]. J Autoimmun，2018，94：90-98.
[25] Xiong Y，Ran J，Xu L，et al. Reactivation of NR4A1 Restrains Chondrocyte Inflammation and Ameliorates Osteoarthritis in Rats [J]. Front Cell Dev Biol，2020，8：158.
[26] Shi X，Ye H，Yao X，et al. The involvement and possible mechanism of NR4A1 in chondrocyte apoptosis during osteoarthritis [J]. Am J Transl Res，2017，9（2）：746-754.
[27] Kinoshita T，Hashimoto T，Sogabe Y，et al. High-resolution structure discloses the potential for allosteric regulation of mitogen-activated protein kinase kinase 7 [J]. Biochem Biophys Res Commun，2017，493（1）：313-317.
[28] Peng HZ，Yun Z，Wang W，et al. Dual specificity phosphatase 1 has a protective role in osteoarthritis fibroblast-like synoviocytes via inhibition of the MAPK signaling pathway [J]. Mol Med Rep，2017，16（6）：8441-8447.
[29] Wang J，Zhou JY，Kho D，et al. Role for DUSP1（dual-specificity protein phosphatase 1）in the regulation of autophagy [J]. Autophagy，2016，12（10）：1791-1803.