Compression Promotes the Osteogenic Differentiation of Human Periodontal Ligament Stem Cells by Regulating METTL14-mediated IGF1


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Abstract

Background and Objectives::Orthodontic treatment involves the application of mechanical force to induce periodontal tissue remodeling and ultimately promote tooth movement. It is essential to study the response mechanisms of human periodontal ligament stem cells (hPDLSCs) to improve orthodontic treatment.

Methods::In this study, hPDLSCs treated with compressive force were used to simulate orthodontic treatment. Cell viability and cell death were assessed using the CCK-8 assay and TUNEL staining. Alkaline phosphatase (ALP) and alizarin red staining were performed to evaluate osteogenic differentiation. The binding relationship between IGF1 and METTL14 was assessed using RIP and dual-luciferase reporter assays.

Results::The compressive force treatment promoted the viability and osteogenic differentiation of hPDLSCs. Additionally, m6A and METTL14 levels in hPDLSCs increased after compressive force treatment, whereas METTL14 knockdown decreased cell viability and inhibited the osteogenic differentiation of hPDLSCs treated with compressive force. Furthermore, the upregulation of METTL14 increased m6A levels, mRNA stability, and IGF1 expression. RIP and dual-luciferase reporter assays confirmed the interaction between METTL14 and IGF1. Furthermore, rescue experiments demonstrated that IGF1 overexpression reversed the effects of METTL14 knockdown in hPDLSCs treated with compressive force.

Conclusions::In conclusion, this study demonstrated that compressive force promotes cell viability and osteogenic differentiation of hPDLSCs by regulating IGF1 levels mediated by METTL14.

About the authors

Zengbo Wu

, North Sichuan Medical College, Xinglin Community

Author for correspondence.
Email: info@benthamscience.net

References

  1. Uhlir R, Mayo V, Lin PH, et al. Biomechanical characterization of the periodontal ligament: Orthodontic tooth movement. Angle Orthod 2017; 87(2): 183-92. doi: 10.2319/092615-651.1 PMID: 27542105
  2. Li Y, Jacox LA, Little SH, Ko CC. Orthodontic tooth movement: The biology and clinical implications. Kaohsiung J Med Sci 2018; 34(4): 207-14. doi: 10.1016/j.kjms.2018.01.007 PMID: 29655409
  3. Liu Y, Ai Y, Sun X, et al. Interleukin-20 acts as a promotor of osteoclastogenesis and orthodontic tooth movement. Stem Cells Int 2021; 2021: 1-20. doi: 10.1155/2021/5539962 PMID: 34122555
  4. Dutra EH, Nanda R, Yadav S. Bone response of loaded periodontal ligament. Curr Osteoporos Rep 2016; 14(6): 280-3. doi: 10.1007/s11914-016-0328-x PMID: 27681936
  5. Lin J, Huang J, Zhang Z, Yu X, Cai X, Liu C. Periodontal ligament cells under mechanical force regulate local immune homeostasis by modulating Th17/Treg cell differentiation. Clin Oral Investig 2022; 26(4): 3747-64. doi: 10.1007/s00784-021-04346-0 PMID: 35029749
  6. Li Y, Zhan Q, Bao M, Yi J, Li Y. Biomechanical and biological responses of periodontium in orthodontic tooth movement: Up-date in a new decade. Int J Oral Sci 2021; 13(1): 20-0. doi: 10.1038/s41368-021-00125-5 PMID: 34183652
  7. Ahmed T, Rahman NA, Alam MK. Comparison of orthodontic bracket debonding force and bracket failure pattern on different teeth in vivo by a prototype debonding device. BioMed Res Int 2021; 2021: 1-7. doi: 10.1155/2021/6663683 PMID: 33959664
  8. Shi DL, Grifone R. RNA-binding proteins in the post-transcriptional control of skeletal muscle development, regeneration and disease. Front Cell Dev Biol 2021; 9: 738978. doi: 10.3389/fcell.2021.738978 PMID: 34616743
  9. Wang X, Wu R, Liu Y, et al. m 6 A mRNA methylation controls autophagy and adipogenesis by targeting Atg5 and Atg7. Autophagy 2020; 16(7): 1221-35. doi: 10.1080/15548627.2019.1659617 PMID: 31451060
  10. Xie Q, Wu TP, Gimple RC, et al. N-methyladenine DNA modification in glioblastoma. Cell 2018; 175(5): 1228-1243.e20. doi: 10.1016/j.cell.2018.10.006 PMID: 30392959
  11. Ma S, Chen C, Ji X, et al. The interplay between m6A RNA methylation and noncoding RNA in cancer. J Hematol Oncol 2019; 12(1): 121-1. doi: 10.1186/s13045-019-0805-7 PMID: 31757221
  12. Liu X, Qin J, Gao T, et al. Analysis of METTL3 and METTL14 in hepatocellular carcinoma. Aging 2020; 12(21): 21638-59. doi: 10.18632/aging.103959 PMID: 33159022
  13. Yang X, Zhang S, He C, et al. METTL14 suppresses proliferation and metastasis of colorectal cancer by down-regulating oncogenic long non-coding RNA XIST. Mol Cancer 2020; 19(1): 46. doi: 10.1186/s12943-020-1146-4 PMID: 32111213
  14. Jian D, Wang Y, Jian L, et al. METTL14 aggravates endothelial inflammation and atherosclerosis by increasing FOXO1 N6-methyladeosine modifications. Theranostics 2020; 10(20): 8939-56. doi: 10.7150/thno.45178 PMID: 32802173
  15. Weng H, Huang H, Wu H, et al. METTL14 inhibits hematopoietic stem/progenitor differentiation and promotes leukemogenesis via mRNA m6A modification. Cell Stem Cell 2018; 22(2): 191-205.e9. doi: 10.1016/j.stem.2017.11.016 PMID: 29290617
  16. Wang M, Liu J, Zhao Y, et al. Upregulation of METTL14 mediates the elevation of PERP mRNA N6 adenosine methylation promoting the growth and metastasis of pancreatic cancer. Mol Cancer 2020; 19(1): 130. doi: 10.1186/s12943-020-01249-8 PMID: 32843065
  17. Qiao C, Huang W, Chen J, et al. IGF1-mediated HOXA13 overexpression promotes colorectal cancer metastasis through upregulating ACLY and IGF1R. Cell Death Dis 2021; 12(6): 564. doi: 10.1038/s41419-021-03833-2 PMID: 34075028
  18. Higashi Y, Gautam S, Delafontaine P, Sukhanov S. IGF-1 and cardiovascular disease. Growth Horm IGF Res 2019; 45: 6-16. doi: 10.1016/j.ghir.2019.01.002 PMID: 30735831
  19. Li Z, Pan W, Shen Y, et al. IGF1/IGF1R and microRNA let-7e down-regulate each other and modulate proliferation and migration of colorectal cancer cells. Cell Cycle 2018; 17(10): 1212-9. doi: 10.1080/15384101.2018.1469873 PMID: 29886785
  20. Liu Y, Liu C, Zhang A, et al. Down-regulation of long non-coding RNA MEG3 suppresses osteogenic differentiation of periodontal ligament stem cells (PDLSCs) through miR-27a-3p/IGF1 axis in periodontitis. Aging 2019; 11(15): 5334-50. doi: 10.18632/aging.102105 PMID: 31398715
  21. Sant'Ana ACP, Marques MM, Barroso EC, Passanezi E, de Rezende MLR. Effects of TGF-beta1, PDGF-BB, and IGF-1 on the rate of proliferation and adhesion of a periodontal ligament cell lineage in vitro. Journal of periodontology (1970) 2007; 78(10): 2007-17.
  22. Nimeri G, Kau CH, Abou-Kheir NS, Corona R. Acceleration of tooth movement during orthodontic treatment-a frontier in Orthodontics. Prog Orthod 2013; 14(1): 42. doi: 10.1186/2196-1042-14-42 PMID: 24326040
  23. Kumar V, Batra P, Sharma K, Raghavan S, Srivastava A. Comparative assessment of the rate of orthodontic tooth movement in adolescent patients undergoing treatment by first bicuspid extraction and en mass retraction, associated with low-frequency mechanical vibrations in passive self-ligating and conventional brackets: A randomized controlled trial. Int Orthod 2020; 18(4): 696-705. doi: 10.1016/j.ortho.2020.08.003 PMID: 33162347
  24. Jónsdóttir SH, Giesen EBW, Maltha JC. The biomechanical behaviour of the hyalinized periodontal ligament in dogs during experimental orthodontic tooth movement. Eur J Orthod 2012; 34(5): 542-6. doi: 10.1093/ejo/cjq186 PMID: 21478299
  25. Rossini G, Parrini S, Castroflorio T, Deregibus A, Debernardi CL. Efficacy of clear aligners in controlling orthodontic tooth movement: A systematic review. Angle Orthod 2015; 85(5): 881-9. doi: 10.2319/061614-436.1 PMID: 25412265
  26. Han Y, Yang Q, Huang Y, et al. Mechanical force inhibited hPDLSCs proliferation with the downregulation of MIR31HG via DNA methylation. Oral Dis 2021; 27(5): 1268-82. doi: 10.1111/odi.13637 PMID: 32890413
  27. Sun Y, Fu J, Lin F, et al. Force-induced nitric oxide promotes osteogenic activity during orthodontic tooth movement in mice. Stem Cells Int 2022; 2022: 1-10. doi: 10.1155/2022/4775445 PMID: 36110889
  28. Zhang Z, He Q, Yang S, Zhao X, Li X, Wei F. Mechanical force-sensitive lncRNA SNHG8 inhibits osteogenic differentiation by regulating EZH2 in hPDLSCs. Cell Signal 2022; 93: 110285. doi: 10.1016/j.cellsig.2022.110285 PMID: 35192931
  29. He M, Lei H, He X, et al. METTL14 regulates osteogenesis of bone marrow mesenchymal stem cells via inducing autophagy through m6A/IGF2BPs/Beclin-1 signal axis. Stem Cells Transl Med 2022; 11(9): 987-1001. doi: 10.1093/stcltm/szac049 PMID: 35980318
  30. Cheng C, Zhang H, Zheng J, Jin Y, Wang D, Dai Z. METTL14 benefits the mesenchymal stem cells in patients with steroid-associated osteonecrosis of the femoral head by regulating the m6A level of PTPN6. Aging 2021; 13(24): 25903-19. doi: 10.18632/aging.203778 PMID: 34910686
  31. Tian F, Wang Y, Bikle DD. IGF-1 signaling mediated cell-specific skeletal mechano-transduction. J Orthop Res 2018; 36(2): 576-83. PMID: 28980721
  32. Feng J, Meng Z. Insulin growth factor 1 promotes the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells through the Wnt/β catenin pathway. Exp Ther Med 2021; 22(2): 891. doi: 10.3892/etm.2021.10323 PMID: 34194569
  33. Yuan Y, Duan R, Wu B, et al. Gene expression profiles and bioinformatics analysis of insulin like growth factor 1 promotion of osteogenic differentiation. Mol Genet Genomic Med 2019; 7(10): e00921. doi: 10.1002/mgg3.921 PMID: 31419079
  34. Rico-Llanos GA, Becerra J, Visser R. Insulin-like growth factor-1 (IGF-1) enhances the osteogenic activity of bone morphogenetic protein-6 (BMP-6) in vitro and in vivo, and together have a stronger osteogenic effect than when IGF-1 is combined with BMP-2. J Biomed Mater Res A 2017; 105(7): 1867-75. doi: 10.1002/jbm.a.36051 PMID: 28256809

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