Long Non-coding RNA DLEU1 Promotes Progression of Osteoarthritis via miR-492/TLR8 Axis


Цитировать

Полный текст

Аннотация

Background:Long non-coding RNAs (LncRNAs) are generally reported to participate in the development of Osteoarthritis (OA) by acting as competing endogenous RNAs (ceRNAs). However, the molecular mechanism is largely unknown. This study aimed to investigate the possible mechanisms contributing to osteoarthritis (OA).

Methods:Four gene expression profiles from patients with OA were downloaded from a public database and integrated to screen important RNAs associated with OA. Differentially expressed (DE) lncRNAs, microRNAs (miRNAs), and mRNAs were filtered, and a ceRNA network was constructed. An in vitro OA model was established by treating chondrocytes with IL-1β. The expression levels of MMP-13, COL2A1, aggrecan, and RUNX2 were detected by qRT-PCR and western blot. Cell proliferation ability was detected by CCK-8 assay. Flow cytometry was used for apoptosis assay. A dual luciferase reporter gene was used to confirm the relationship between DLEU1, miR-492, and TLR8

Results:An OA-related ceRNA network, including 11 pathways, 3 miRNAs, 7 lncRNAs, and 16 mRNAs, was constructed. DLEU1 and TLR8 were upregulated, and miR-492 was downregulated in IL-1β-induced chondrocytes. Overexpression of DLEU1 suppressed viability and promoted apoptosis and extracellular matrix (ECM) degradation in IL-1β induced chondrocytes. Luciferase reporter assay validated the regulatory relations among DLEU1, miR-492, and TLR8. Further study revealed that the effects of DLEU1 on chondrocytes could be reversed by miR-492.

Conclusion:DLEU1 may be responsible for the viability, apoptosis, and ECM degradation in OA via miR-492/TLR8 axis

Об авторах

Chenzhe Ni

Department of Orthopedic Surgery, Qidong People’s Hospital, Nantong University

Email: info@benthamscience.net

Wanglin Zhang

Department of Orthopaedics, Shanghai Children’s Medical Center, Shanghai Jiaotong University School of Medicine

Email: info@benthamscience.net

Sai Qiu

Department of Orthopedic Surgery, Qidong People’s Hospital, Nantong University

Автор, ответственный за переписку.
Email: info@benthamscience.net

Hao Cheng

Department of Orthopedic Surgery, Qidong People’s Hospital, Nantong University

Автор, ответственный за переписку.
Email: info@benthamscience.net

Chunhui Ma

Department of Orthopedic Surgery, Shanghai General Hospital, Shanghai Jiao Tong University

Автор, ответственный за переписку.
Email: info@benthamscience.net

Список литературы

  1. Allen, K.D.; Choong, P.F.; Davis, A.M.; Dowsey, M.M.; Dziedzic, K.S.; Emery, C.; Hunter, D.J.; Losina, E.; Page, A.E.; Roos, E.M.; Skou, S.T.; Thorstensson, C.A.; van der Esch, M.; Whittaker, J.L. Osteoarthritis: Models for appropriate care across the disease continuum. Best Pract. Res. Clin. Rheumatol., 2016, 30(3), 503-535. doi: 10.1016/j.berh.2016.09.003 PMID: 27886944
  2. Poole, A.R. Osteoarthritis as a whole joint disease. HSS J., 2012, 8(1), 4-6. doi: 10.1007/s11420-011-9248-6 PMID: 23372516
  3. Allen, K.D.; Thoma, L.M.; Golightly, Y.M. Epidemiology of osteoarthritis. Osteoarthritis Cartilage, 2022, 30(2), 184-195. doi: 10.1016/j.joca.2021.04.020 PMID: 34534661
  4. Foster, N.E.; Eriksson, L.; Deveza, L.; Hall, M. Osteoarthritis year in review 2022: Epidemiology & therapy. Osteoarthritis Cartilage, 2023, 31(7), 876-883. doi: 10.1016/j.joca.2023.03.008 PMID: 36963607
  5. Yao, Q.; Wu, X.; Tao, C.; Gong, W.; Chen, M.; Qu, M.; Zhong, Y.; He, T.; Chen, S.; Xiao, G. Osteoarthritis: Pathogenic signaling pathways and therapeutic targets. Signal Transduct. Target. Ther., 2023, 8(1), 56. doi: 10.1038/s41392-023-01330-w PMID: 36737426
  6. Giorgino, R.; Albano, D.; Fusco, S.; Peretti, G.M.; Mangiavini, L.; Messina, C. Knee osteoarthritis: Epidemiology, pathogenesis, and mesenchymal stem cells: What else is new? an update. Int. J. Mol. Sci., 2023, 24(7), 6405. doi: 10.3390/ijms24076405 PMID: 37047377
  7. Majeed, MH; Sherazi, SAA; Bacon, D; Bajwa, ZH Pharmacological treatment of pain in osteoarthritis: A descriptive review., Curr Rheumatol Rep., 2018, 20(12), 018-0794. doi: 10.1007/s11926-018-0794-5
  8. Carlson, V.R.; Ong, A.C.; Orozco, F.R.; Hernandez, V.H.; Lutz, R.W.; Post, Z.D. Compliance with the AAOS guidelines for treatment of osteoarthritis of the knee: A survey of the American association of hip and knee surgeons. J. Am. Acad. Orthop. Surg., 2018, 26(3), 103-107. doi: 10.5435/JAAOS-D-17-00164 PMID: 29283898
  9. Smith, M.D. The normal synovium. Open Rheumatol. J., 2011, 5, 100-106. doi: 10.2174/1874312901105010100 PMID: 22279508
  10. Bondeson, J.; Blom, A.B.; Wainwright, S.; Hughes, C.; Caterson, B.; van den Berg, W.B. The role of synovial macrophages and macrophage‐produced mediators in driving inflammatory and destructive responses in osteoarthritis. Arthritis Rheum., 2010, 62(3), 647-657. doi: 10.1002/art.27290 PMID: 20187160
  11. Pettenuzzo, S.; Arduino, A.; Belluzzi, E.; Pozzuoli, A.; Fontanella, C.G.; Ruggieri, P.; Salomoni, V.; Majorana, C.; Berardo, A. Biomechanics of chondrocytes and chondrons in healthy conditions and osteoarthritis: A review of the mechanical characterisations at the microscale. Biomedicines, 2023, 11(7), 1942. doi: 10.3390/biomedicines11071942 PMID: 37509581
  12. Belluzzi, E.; Todros, S.; Pozzuoli, A.; Ruggieri, P.; Carniel, E.L.; Berardo, A. Human cartilage biomechanics: Experimental and theoretical approaches towards the identification of mechanical properties in healthy and osteoarthritic conditions. Processes, 2023, 11(4), 1014. doi: 10.3390/pr11041014
  13. Emmi, A.; Stocco, E.; Boscolo-Berto, R.; Contran, M.; Belluzzi, E.; Favero, M.; Ramonda, R.; Porzionato, A.; Ruggieri, P.; De Caro, R.; Macchi, V. Infrapatellar fat pad-synovial membrane anatomo-fuctional unit: Microscopic basis for piezo1/2 mechanosensors involvement in osteoarthritis pain. Front. Cell Dev. Biol., 2022, 10, 886604. doi: 10.3389/fcell.2022.886604 PMID: 35837327
  14. Krawetz, R.J.; Wu, Y.E.; Bertram, K.L.; Shonak, A.; Masson, A.O.; Ren, G.; Leonard, C.; Kapoor, M.; Matyas, J.R.; Salo, P.T. Synovial mesenchymal progenitor derived aggrecan regulates cartilage homeostasis and endogenous repair capacity. Cell Death Dis., 2022, 13(5), 470. doi: 10.1038/s41419-022-04919-1 PMID: 35585042
  15. Lai, C.; Liao, B.; Peng, S.; Fang, P.; Bao, N.; Zhang, L. Synovial fibroblast-miR-214-3p-derived exosomes inhibit inflammation and degeneration of cartilage tissues of osteoarthritis rats. Mol. Cell. Biochem., 2023, 478(3), 637-649. doi: 10.1007/s11010-022-04535-9 PMID: 36001206
  16. Wang, L.; Cho, K.B.; Li, Y.; Tao, G.; Xie, Z.; Guo, B. Long noncoding RNA (lncRNA)-mediated competing endogenous RNA networks provide novel potential biomarkers and therapeutic targets for colorectal cancer. Int. J. Mol. Sci., 2019, 20(22), 5758. doi: 10.3390/ijms20225758 PMID: 31744051
  17. 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), 018-0746.
  18. Li, Y.; Li, S.; Luo, Y.; Liu, Y.; Yu, N. LncRNA PVT1 regulates chondrocyte apoptosis in osteoarthritis by acting as a sponge for miR-488-3p. DNA Cell Biol., 2017, 36(7), 571-580. doi: 10.1089/dna.2017.3678 PMID: 28520497
  19. Du, Z.; Sun, T.; Hacisuleyman, E.; Fei, T.; Wang, X.; Brown, M.; Rinn, J.L.; Lee, M.G.S.; Chen, Y.; Kantoff, P.W.; Liu, X.S. Integrative analyses reveal a long noncoding RNA-mediated sponge regulatory network in prostate cancer. Nat. Commun., 2016, 7(1), 10982. doi: 10.1038/ncomms10982 PMID: 26975529
  20. Karreth, FA; Reschke, M; Ruocco, A; Ng, C; Chapuy, B; Léopold, V; Sjoberg, M; Keane, TM; Verma, A; Ala, U; Tay, Y; Wu, D; Seitzer, N The BRAF pseudogene functions as a competitive endogenous RNA and induces lymphoma in vivo. cell, 2015, 161(2), 319-332.
  21. Liu, N.; Huang, Y.; Shao, Y.; Fan, X.; Sun, H.; Wang, T.; Yao, T.; Chen, X.Y. The regulatory role and mechanism of lncTUG1 on cartilage apoptosis and inflammation in osteoarthritis. Arthritis Res. Ther., 2023, 25(1), 106. doi: 10.1186/s13075-023-03087-7 PMID: 37340458
  22. Barrett, T.; Wilhite, S.E.; Ledoux, P.; Evangelista, C.; Kim, I.F.; Tomashevsky, M.; Marshall, K.A.; Phillippy, K.H.; Sherman, P.M.; Holko, M.; Yefanov, A.; Lee, H.; Zhang, N.; Robertson, C.L.; Serova, N.; Davis, S.; Soboleva, A. NCBI GEO: Archive for functional genomics data sets--update. Nucleic Acids Res., 2013, 41(Database issue), D991-D995. PMID: 23193258
  23. Wang, X.; Kang, D.D.; Shen, K.; Song, C.; Lu, S.; Chang, L.C.; Liao, S.G.; Huo, Z.; Tang, S.; Ding, Y.; Kaminski, N.; Sibille, E.; Lin, Y.; Li, J.; Tseng, G.C. An R package suite for microarray meta-analysis in quality control, differentially expressed gene analysis and pathway enrichment detection. Bioinformatics, 2012, 28(19), 2534-2536. doi: 10.1093/bioinformatics/bts485 PMID: 22863766
  24. Langfelder, P.; Horvath, S. WGCNA: An R package for weighted correlation network analysis. BMC Bioinformatics, 2008, 9(1), 559. doi: 10.1186/1471-2105-9-559 PMID: 19114008
  25. Paraskevopoulou, M.D.; Vlachos, I.S.; Karagkouni, D.; Georgakilas, G.; Kanellos, I.; Vergoulis, T.; Zagganas, K.; Tsanakas, P.; Floros, E.; Dalamagas, T.; Hatzigeorgiou, A.G. DIANA-LncBase v2: Indexing microRNA targets on non-coding transcripts. Nucleic Acids Res., 2016, 44(D1), D231-D238. doi: 10.1093/nar/gkv1270 PMID: 26612864
  26. Li, J.H.; Liu, S.; Zhou, H.; Qu, L.H.; Yang, J.H. starBase v2.0: Decoding miRNA-ceRNA, miRNA-ncRNA and protein–RNA interaction networks from large-scale CLIP-Seq data. Nucleic Acids Res., 2014, 42(D1), D92-D97. doi: 10.1093/nar/gkt1248 PMID: 24297251
  27. Shannon, P.; Markiel, A.; Ozier, O.; Baliga, N.S.; Wang, J.T.; Ramage, D.; Amin, N.; Schwikowski, B.; Ideker, T. Cytoscape: A software environment for integrated models of biomolecular interaction networks. Genome Res., 2003, 13(11), 2498-2504. doi: 10.1101/gr.1239303 PMID: 14597658
  28. Huang, D.W.; Sherman, B.T.; Lempicki, R.A. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat. Protoc., 2009, 4(1), 44-57. doi: 10.1038/nprot.2008.211 PMID: 19131956
  29. Davis, A.P.; Wiegers, T.C.; Johnson, R.J.; Sciaky, D.; Wiegers, J.; Mattingly, C.J. Comparative Toxicogenomics Database (CTD): Update 2023. Nucleic Acids Res., 2023, 51(D1), D1257-D1262. doi: 10.1093/nar/gkac833 PMID: 36169237
  30. Sanchez-Lopez, E.; Coras, R.; Torres, A.; Lane, N.E.; Guma, M. Synovial inflammation in osteoarthritis progression. Nat. Rev. Rheumatol., 2022, 18(5), 258-275. doi: 10.1038/s41584-022-00749-9 PMID: 35165404
  31. Kanthawang, T.; Bodden, J.; Joseph, G.B.; Lane, N.E.; Nevitt, M.; McCulloch, C.E.; Link, T.M. Obese and overweight individuals have greater knee synovial inflammation and associated structural and cartilage compositional degeneration: Data from the osteoarthritis initiative. Skeletal Radiol., 2021, 50(1), 217-229. doi: 10.1007/s00256-020-03550-5 PMID: 32699956
  32. Tay, Y.; Rinn, J.; Pandolfi, P.P. The multilayered complexity of ceRNA crosstalk and competition. Nature, 2014, 505(7483), 344-352. doi: 10.1038/nature12986 PMID: 24429633
  33. Liu, T.; Han, Z.; Li, H.; Zhu, Y.; Sun, Z.; Zhu, A. LncRNA DLEU1 contributes to colorectal cancer progression via activation of KPNA3. Mol Cancer, 2018, 17(1), 018-0873. doi: 10.1186/s12943-018-0873-2
  34. Feng, L.; He, M.; Rao, M.; Diao, J.; Zhu, Y. Long noncoding RNA DLEU1 aggravates glioma progression via the miR-421/MEF2D axis. OncoTargets Ther., 2019, 12, 5405-5414. doi: 10.2147/OTT.S207542 PMID: 31360066
  35. Li, Q.; Zhang, Z.; Jiang, H.; Hou, J.; Chai, Y.; Nan, H.; Li, F.; Wang, L. DLEU1 promotes cell survival by preventing DYNLL1 degradation in esophageal squamous cell carcinoma. J. Transl. Med., 2022, 20(1), 245. doi: 10.1186/s12967-022-03449-w PMID: 35619131
  36. Hatanaka, Y.; Niinuma, T.; Kitajima, H.; Nishiyama, K.; Maruyama, R.; Ishiguro, K.; Toyota, M.; Yamamoto, E.; Kai, M.; Yorozu, A.; Sekiguchi, S.; Ogi, K.; Dehari, H.; Idogawa, M.; Sasaki, Y.; Tokino, T.; Miyazaki, A.; Suzuki, H. DLEU1 promotes oral squamous cell carcinoma progression by activating interferon-stimulated genes. Sci. Rep., 2021, 11(1), 20438. doi: 10.1038/s41598-021-99736-5 PMID: 34650128
  37. Ma, H.N.; Chen, H.J.; Liu, J.Q.; Li, W.T. Long non-coding RNA DLEU1 promotes malignancy of breast cancer by acting as an indispensable coactivator for HIF-1α-induced transcription of CKAP2. Cell Death Dis., 2022, 13(7), 625. doi: 10.1038/s41419-022-04880-z PMID: 35853854
  38. Wu, X.; Yin, S.; Yan, L.; Liu, Y.; Shang, L.; Liu, J. lncRNA DLEU1 modulates proliferation, inflammation, and extracellular matrix degradation of chondrocytes through regulating miR-671-5p. J. Immunol. Res., 2022, 2022, 1-12. doi: 10.1155/2022/1816217 PMID: 35647200
  39. Wang, Y.; Chen, L.Y.; Liu-Bryan, R. Mitochondrial biogenesis, activity, and DNA isolation in chondrocytes. Methods Mol. Biol., 2021, 2245, 195-213. doi: 10.1007/978-1-0716-1119-7_14 PMID: 33315204
  40. Barreto, G.; Manninen, M.; K Eklund, K. Osteoarthritis and toll-like receptors: When innate immunity meets chondrocyte apoptosis. Biology, 2020, 9(4), 65. doi: 10.3390/biology9040065 PMID: 32235418
  41. Li, Y.; Nie, J.; Deng, C.; Li, H. P-15 promotes chondrocyte proliferation in osteoarthritis by regulating SFPQ to target the Akt-RUNX2 axis. J. Orthop. Surg. Res., 2023, 18(1), 199. doi: 10.1186/s13018-023-03658-z PMID: 36915153
  42. Okada, A.; Okada, Y. Progress of research in osteoarthritis. Metalloproteinases in osteoarthritis. Clin. Calcium, 2009, 19(11), 1593-1601. PMID: 19880991
  43. Matyas, J.R.; Adams, M.E.; Huang, D.; Sandell, L.J. Discoordinate gene expression of aggrecan and type ii collagen in experimental osteoarthritis. Arthritis Rheum., 1995, 38(3), 420-425. doi: 10.1002/art.1780380320 PMID: 7533495
  44. Long, F. Building strong bones: Molecular regulation of the osteoblast lineage. Nat. Rev. Mol. Cell Biol., 2012, 13(1), 27-38. doi: 10.1038/nrm3254 PMID: 22189423
  45. Chang, S.M.; Hu, W.W. Long non‐coding RNA MALAT1 promotes oral squamous cell carcinoma development via microRNA‐125b/STAT3 axis. J. Cell. Physiol., 2018, 233(4), 3384-3396. doi: 10.1002/jcp.26185 PMID: 28926115
  46. Broz, P.; Monack, D.M. Newly described pattern recognition receptors team up against intracellular pathogens. Nat. Rev. Immunol., 2013, 13(8), 551-565. doi: 10.1038/nri3479 PMID: 23846113
  47. Miller, R.E.; Scanzello, C.R.; Malfait, A-M. An emerging role for Toll-like receptors at the neuroimmune interface in osteoarthritis. In: Seminars in Immunopathology; Springer, 2019; pp. 583-594.

Дополнительные файлы

Доп. файлы
Действие
1. JATS XML

© Bentham Science Publishers, 2024