LncRNA uc.48<sup>+</sup>通过激活P2X7R/NF-κB通路促进骨关节炎软骨组织的炎症

doi:10.3969/j.issn.1006-6233.2022.02.07

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Abstract Objective: To study the regulatory effect of LncRNA uc.48⁺ on inflammation of knee osteoarthritis (OA) and explore its mechanism. Methods: Sodium iodoacetate (MIA) was injected into the joint cavity to induce OA in SD rats. The mechanical withdrawal threshold (MWT) and paw withdrawal thermal latency (PWTL) on the injection side of the knee joint were recorded within 21 days after injection. OS staining was used to observe the pathological changes of 21d joint tissues, and real-time quantitative PCR (qRT-PCR) was used to detect the levels of cartilage LncRNA uc.48⁺ and P2X7R. Plasmid pcDNA3.1 was used to construct LncRNA uc.48⁺ overexpression vector (pc-LncRNA uc.48⁺) and empty vector (pc-null). The rats were divided into sham group (n=10) and MIA group (n=50). Among them, 40 rats were randomly selected from the MIA group and randomly divided into pc-null group, pc-LncRNAuc.48⁺ group, pc-LncRNA uc .48⁺+ Nucleotide P2X receptor (P2X7R) channel antagonist (AZD9056) group, pc-LncRNA uc.48⁺+ nuclear factor κB (NF-κB) inhibitor (Helenalin) group (n=10). Western blot was used to detect the levels of P2X7R, P65, phosphorylated P65 (p-P65), matrix metalloproteinase (MMP)-13 and substance P (SP) in the above groups. ELISA was used to detect cartilage tissue prostaglandin (PG) E2, tumor necrosis factor (TNF)-α, and interleukin (IL)-1β. In vitro chondrocytes were transfected with pc-LncRNA uc.48⁺ or pc-null for 24h to detect the expression of P2X7R, P65, and p-P65. Results: Compared with the pre-modeling, MWT and PWTL of rats after 1d-21d of MIA injection decreased, and the joint PGE2, TNF-α, IL-1β all increased (all P<0.05). LncRNA uc.48⁺ continued to be up-regulated from 1d to 21d in the MIA group, and P2X7R mRNA was also up-regulated (all P<0.05). In MIA rats, the levels of PGE2, TNF-α, IL-1β, P2X7R, P65, and p-P65 in the pc-LncRNAuc. 48⁺ group were higher than those in the pc-null group (all P<0.05), while the levels of PGE2, TNF-α, IL-1β, P65, p-P65, MMP-13 and SP in the uc.48⁺+AZD9056 group were lower than those in the pc-LncRNAuc.48⁺ group (all P<0.05). In addition, the levels of PGE2, TNF-α, IL-1β, MMP-13 and SP in the pc-LncRNA uc.48⁺+ Helenalin group were lower than those in the pc-LncRNAuc.48⁺ group (all P<0.05). However, the P2X7R level of the pc-LncRNA uc.48⁺+ Helenalin group and the pc-LncRNAuc.48⁺ group were not different (P>0.05). Conclusion: LncRNA uc.48⁺ promotes the inflammation of osteoarthritis cartilage tissue by activating the P2X7R/NF-κB signaling pathway.

Key words： LncRNA uc.48⁺ Nucleotide P2X receptor 7 Nuclear factor kappa B Osteoarthritis

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	LIU Jingxin
	CHEN Yuxing
	WANG Gui

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LIU Jingxin,CHEN Yuxing,WANG Gui. LncRNA UC.48⁺ Promotes Cartilage Inflammation in Osteoarthritis by Activating the P2X7R/NF-κB Pathway[J]. HeBei Med, 2022, 28(2): 213-219.

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http://www.hbyxzzs.cn/EN/10.3969/j.issn.1006-6233.2022.02.07 OR http://www.hbyxzzs.cn/EN/Y2022/V28/I2/213

[1] Hawker GA.Osteoarthritis is a serious disease[J].Clin Exp Rheumatol,2019,120(5):3~6.
[2] Buttgereit F,Burmester GR,Bijlsma JW.Non-surgical management of knee osteoarthritis:where are we now and where do we need to go[J]RMD Open,2015,1(1):1~12.
[3] Alves LA,Bezerra RJ,Faria RX,et al.Physiological roles and potential therapeutic applications of the P2X7 receptor in inflammation and pain[J].Molecules,2013,18(9):10953~10972.
[4] Bhat SA,Ahmad SM,Mumtaz PT,et al.Long non-coding RNAs:mechanism of action and functional utility [J].Noncoding RNA Res,2016,1(1):43~50.
[5] Wu Y,Lu X,Shen B,et al.The therapeutic potential and role of miRNA,lncRNA,and circRNA in osteoarthritis[J].Curr Gene Ther,2019,19(4):255~263.
[6] Wu B,Zhang C,Zou L,et al.LncRNA uc.48⁺ siRNA improved diabetic sympathetic neuropathy in type 2 diabetic rats mediated by P2X7 receptor in SCG [J].Auton Neurosci,2016,197(1):14~18.
[7] Wu H,Wen F,Jiang M,et al.LncRNA uc.48⁺ is involved in the diabetic immune and inflammatory responses mediated by P2X7 receptor in RAW264.7 macrophages[J].Int Mol Med,2018,42(1):1152~1160.
[8] Schmitt M,Sturmheit AS,Welk A,et al.Procedures for the quantitative protein determination of urokinase and its inhibitor,PAI-1,in human breast cancer tissue extracts by ELISA[J].Methods Mol Med,2006,120(1):245~265.
[9] Wu S,Yi Z,Ling M,et al.DR4-associated death receptor signal promotes cartilage damage in patients with kashin-beck disease[J].Cartilage,2019,150(1):1~12.
[10] Liao K,Xu J,Yang W,et al.The research progress of LncRNA involved in the regulation of inflammatory diseases[J].Mol Immunol,2018,101(1):182~188.
[11] Keystone EC,Wang MM,Layton M,et al Clinical evaluation of the efficacy of the P2X7 purinergic receptor antagonist AZD9056 on the signs and symptoms of rheumatoid arthritis in patients with active disease despite treatment with methotrexate or sulphasalazine [J].Ann Rheum Dis,2012,71(10):1630~635.
[12] Zheng L,Zhang Z,Sheng P,et al.The role of metabolism in chondrocyte dysfunction and the progression of osteoarthritis[J].Ageing Res Rev,2021,66(1):1~13.
[13] Mehana EE,Khafaga AF,El-Blehi SS.The role of matrix metalloproteinases in osteoarthritis pathogenesis:An updated review[J].Life Sci,2019,234(1):1~10.
[14] Yu Y,Feng S,Wei S,et al.Extracellular ATP activates P2X7R-NF-κB (p65) pathway to promote the maturation of bone marrow-derived dendritic cells of mice[J].Cytokine,2019,119(1):175~181.
[15] Yang C,Shi S,Su Y,et al.P2X7R promotes angiogenesis and tumour-associated macrophage recruitment by regulating the NF-κB signalling pathway in colorectal cancer cells[J].Cell Mol Med,2020,24(18):10830~10841.