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Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

General Research Article

Inhibition of Long Non-coding RNA CTD-2574D22.4 Alleviates LPS-induced Apoptosis and Inflammatory Injury of Chondrocytes

Author(s): Lisong Li*, Lianfang Zhang*, Yong Zhang*, Dinghua Jiang, Wu Xu, Haiyue Zhao and Lixin Huang

Volume 25 , Issue 27 , 2019

Page: [2969 - 2974] Pages: 6

DOI: 10.2174/1381612825666190801141801

Price: $65

Abstract

Background: Osteoarthritis (OA) is a common joint disease characterized by cartilage degeneration. Long non-coding RNAs (lncRNAs) have been associated with inflammatory diseases, including OA. Here, we investigated the potential molecular role of lncRNAs in OA pathogenesis.

Methods: ATDC5 cells were treated with lipopolysaccharides (LPS), and qPCR was used to identify and determine expression of potential lncRNAs involved in LPS-induced chondrocyte injury. Cell viability, apoptosis, and expression of cartilage-related genes and inflammatory cytokines were assessed after CTD-2574D22.4 knockdown.

Results: After LPS stimulation, CTD-2574D22.4 was found to be the second highest up-regulated gene, and the enhanced expression was validated in OA chondrocytes. Moreover, CTD-2574D22.4 inhibition significantly rescued cell viability, suppressed by LPS stress, and markedly attenuated LPS-induced apoptosis. The expression of cartilage-degrading enzymes MMP-13 and ADAMTS-5 were increased, while type II collagen was reduced after LPS treatment. This trend was largely reversed by CTD-2574D22.4 knockdown. Additionally, mRNA and protein levels of key inflammatory cytokines (TNF-a, IL-6, and IL-1β) were significantly elevated in the LPS group and partially relieved upon CTD-2574D22.4 knockdown.

Conclusion: CTD2574D22.4 knockdown ameliorates LPS-induced cartilage injury by protecting chondrocytes from apoptosis via anti-inflammation and anti- cartilage-degrading pathways. Thus, CTD2574D22.4 might be a potential diagnostic and therapeutic target for OA.

Keywords: Osteoarthritis, LncRNA, CTD-2574D22.4, apoptosis, inflammatory injury, cartilage degeneration.

[1]
Okubo M, Okada Y. Destruction of the articular cartilage in osteoarthritis. Clin Calcium 2013; 23(12): 1705-13.
[PMID: 24292524]
[2]
Bijlsma JW, Berenbaum F, Lafeber FP. Osteoarthritis: an update with relevance for clinical practice. Lancet 2011; 377(9783): 2115-26.
[http://dx.doi.org/10.1016/S0140-6736(11)60243-2] [PMID: 21684382]
[3]
Loeser RF, Goldring SR, Scanzello CR, Goldring MB. Osteoarthritis: a disease of the joint as an organ. Arthritis Rheum 2012; 64(6): 1697-707.
[http://dx.doi.org/10.1002/art.34453] [PMID: 22392533]
[4]
Cross M, Smith E, Hoy D, et al. The global burden of hip and knee osteoarthritis: estimates from the global burden of disease 2010 study. Ann Rheum Dis 2014; 73(7): 1323-30.
[http://dx.doi.org/10.1136/annrheumdis-2013-204763] [PMID: 24553908]
[5]
Schnitzer TJ, Ekman EF, Spierings EL, et al. Efficacy and safety of tanezumab monotherapy or combined with non-steroidal anti-inflammatory drugs in the treatment of knee or hip osteoarthritis pain. Ann Rheum Dis 2015; 74(6): 1202-11.
[http://dx.doi.org/10.1136/annrheumdis-2013-204905] [PMID: 24625625]
[6]
van der Kraan PM. Osteoarthritis year 2012 in review: biology. Osteoarthritis Cartilage 2012; 20(12): 1447-50.
[http://dx.doi.org/10.1016/j.joca.2012.07.010] [PMID: 22897882]
[7]
Ponting CP, Oliver PL, Reik W. Evolution and functions of long noncoding RNAs. Cell 2009; 136(4): 629-41.
[http://dx.doi.org/10.1016/j.cell.2009.02.006] [PMID: 19239885]
[8]
Mercer TR, Dinger ME, Mattick JS. Long non-coding RNAs: insights into functions. Nat Rev Genet 2009; 10(3): 155-9.
[http://dx.doi.org/10.1038/nrg2521] [PMID: 19188922]
[9]
Marques-Rocha JL, Samblas M, Milagro FI, Bressan J, Martínez JA, Marti A. Noncoding RNAs, cytokines, and inflammation-related diseases. FASEB J 2015; 29(9): 3595-611.
[http://dx.doi.org/10.1096/fj.14-260323] [PMID: 26065857]
[10]
Jiang SD, Lu J, Deng ZH, Li YS, Lei GH. Long noncoding RNAs in osteoarthritis. Joint Bone Spine 2017; 84(5): 553-6.
[http://dx.doi.org/10.1016/j.jbspin.2016.09.006] [PMID: 27919571]
[11]
Xing D, Liang JQ, Li Y, et al. Identification of long noncoding RNA associated with osteoarthritis in humans. Orthop Surg 2014; 6(4): 288-93.
[http://dx.doi.org/10.1111/os.12147] [PMID: 25430712]
[12]
Li X, Yu M, Chen L, et al. LncRNA PMS2L2 protects ATDC5 chondrocytes against lipopolysaccharide-induced inflammatory injury by sponging miR-203. Life Sci 2019; 217: 283-92.
[http://dx.doi.org/10.1016/j.lfs.2018.12.020] [PMID: 30550887]
[13]
Li F, Sun J, Huang S, Su G, Pi G. LncRNA GAS5 overexpression reverses LPS-induced inflammatory injury and apoptosis through up-regulating KLF2 expression in ATDC5 chondrocytes. Cell Physiol Biochem 2018; 45(3): 1241-51.
[http://dx.doi.org/10.1159/000487455] [PMID: 29448248]
[14]
Hu J, Wang Z, Shan Y, Pan Y, Ma J, Jia L. Long non-coding RNA HOTAIR promotes osteoarthritis progression via miR-17-5p/FUT2/β-catenin axis. Cell Death Dis 2018; 9(7): 711.
[http://dx.doi.org/10.1038/s41419-018-0746-z] [PMID: 29907764]
[15]
Hu Y, Li S, Zou Y. Knockdown of LncRNA H19 relieves LPS-induced damage by modulating miR-130a in osteoarthritis. Yonsei Med J 2019; 60(4): 381-8.
[http://dx.doi.org/10.3349/ymj.2019.60.4.381] [PMID: 30900425]
[16]
Zhang C, Wang P, Jiang P, et al. Upregulation of lncRNA HOTAIR contributes to IL-1β-induced MMP overexpression and chondrocytes apoptosis in temporomandibular joint osteoarthritis. Gene 2016; 586(2): 248-53.
[http://dx.doi.org/10.1016/j.gene.2016.04.016] [PMID: 27063559]
[17]
Cao L, Wang Y, Wang Q, Huang J. LncRNA FOXD2-AS1 regulates chondrocyte proliferation in osteoarthritis by acting as a sponge of miR-206 to modulate CCND1 expression. Biomed Pharmacother 2018; 106: 1220-6.
[http://dx.doi.org/10.1016/j.biopha.2018.07.048] [PMID: 30119190]
[18]
Lu Z, Luo M, Huang Y. lncRNA-CIR regulates cell apoptosis of chondrocytes in osteoarthritis. J Cell Biochem 2018. In press
[PMID: 30390341]
[19]
Tang LP, Ding JB, Liu ZH, Zhou GJ. LncRNA TUG1 promotes osteoarthritis-induced degradation of chondrocyte extracellular matrix via miR-195/MMP-13 axis. Eur Rev Med Pharmacol Sci 2018; 22(24): 8574-81.
[PMID: 30575896]
[20]
Perotto JH, Camejo FA, Doetzer AD, et al. Expression of MMP-13 in human temporomandibular joint disc derangement and osteoarthritis. Cranio 2018; 36(3): 161-6.
[http://dx.doi.org/10.1080/08869634.2017.1315511] [PMID: 28446077]
[21]
Chen YT, Hou CH, Hou SM, Liu JF. The effects of amphiregulin induced MMP-13 production in human osteoarthritis synovial fibroblast. Mediators Inflamm 2014; 2014759028
[http://dx.doi.org/10.1155/2014/759028] [PMID: 25147440]
[22]
Lim NH, Meinjohanns E, Meldal M, Bou-Gharios G, Nagase H. In vivo imaging of MMP-13 activity in the murine destabilised medial meniscus surgical model of osteoarthritis. Osteoarthritis Cartilage 2014; 22(6): 862-8.
[http://dx.doi.org/10.1016/j.joca.2014.04.006] [PMID: 24747174]
[23]
Kalva S, Saranyah K, Suganya PR, Nisha M, Saleena LM. Potent inhibitors precise to S1′ loop of MMP-13, a crucial target for osteoarthritis. J Mol Graph Model 2013; 44: 297-310.
[http://dx.doi.org/10.1016/j.jmgm.2013.06.005] [PMID: 23938376]
[24]
Ji Q, Xu X, Zhang Q, et al. The IL-1β/AP-1/miR-30a/ADAMTS-5 axis regulates cartilage matrix degradation in human osteoarthritis. J Mol Med (Berl) 2016; 94(7): 771-85.
[http://dx.doi.org/10.1007/s00109-016-1418-z] [PMID: 27067395]
[25]
Miller RE, Tran PB, Ishihara S, Larkin J, Malfait AM. Therapeutic effects of an anti-ADAMTS-5 antibody on joint damage and mechanical allodynia in a murine model of osteoarthritis. Osteoarthritis Cartilage 2016; 24(2): 299-306.
[http://dx.doi.org/10.1016/j.joca.2015.09.005] [PMID: 26410555]
[26]
Li W, Wu M, Jiang S, Ding W, Luo Q, Shi J. Expression of ADAMTs-5 and TIMP-3 in the condylar cartilage of rats induced by experimentally created osteoarthritis. Arch Oral Biol 2014; 59(5): 524-9.
[http://dx.doi.org/10.1016/j.archoralbio.2014.02.016] [PMID: 24632095]
[27]
Shen J, Abu-Amer Y, O’Keefe RJ, McAlinden A. Inflammation and epigenetic regulation in osteoarthritis. Connect Tissue Res 2017; 58(1): 49-63.
[http://dx.doi.org/10.1080/03008207.2016.1208655] [PMID: 27389927]
[28]
Goldring MB, Otero M, Tsuchimochi K, Ijiri K, Li Y. Defining the roles of inflammatory and anabolic cytokines in cartilage metabolism. Ann Rheum Dis 2008; 67(Suppl. 3): iii75-82.
[http://dx.doi.org/10.1136/ard.2008.098764] [PMID: 19022820]
[29]
Scanzello CR. Chemokines and inflammation in osteoarthritis: Insights from patients and animal models. J Orthop Res 2017; 35(4): 735-9.
[http://dx.doi.org/10.1002/jor.23471] [PMID: 27808445]
[30]
Jilani AA, Mackworth-Young CG. The role of citrullinated protein antibodies in predicting erosive disease in rheumatoid arthritis: a systematic literature review and meta-analysis. Int J Rheumatol 2015; 2015728610
[http://dx.doi.org/10.1155/2015/728610] [PMID: 25821469]
[31]
Kapoor M, Martel-Pelletier J, Lajeunesse D, Pelletier JP, Fahmi H. Role of proinflammatory cytokines in the pathophysiology of osteoarthritis. Nat Rev Rheumatol 2011; 7(1): 33-42.
[http://dx.doi.org/10.1038/nrrheum.2010.196] [PMID: 21119608]
[32]
Liang Z, Ren C. Emodin attenuates apoptosis and inflammation induced by LPS through up-regulating lncRNA TUG1 in murine chondrogenic ATDC5 cells. Biomed Pharmacother 2018; 103: 897-902.
[http://dx.doi.org/10.1016/j.biopha.2018.04.085] [PMID: 29710506]

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