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Understanding LncRNAs in Biomaterials Development for Osteointegration

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Regenerative Medicine

Abstract

Osseointegration of implants is a sophisticated healing process comprising of blood clot formation, immune response, angiogenesis, and osteogenesis. The features of the blood clots take a crucial role in fulfilling rapid and satisfying osseointegration. Nano-scaled implant surfaces can dominate the structure, thickness, and coagulation process of blood clots, thereby influencing inflammation and bone regeneration. Long non-coding RNAs (LncRNAs) are actively involved in regulating the transcription of protein-coding genes and have profound effects on a variety of biological processes. This chapter will provide a basic introduction of osseointegration processes and LncRNAs, and focus on the effects of LncRNA profiles within nano-scaled implant surface-mediated blood clots on osseointegration. The sequence analysis of LncRNAs manifests that different titania nanotube arrays (TNAs) can mediate the distinct clot-derived LncRNA expression profiles. Moreover, LncRNAs LOC103346307, LOC103352121, LOC108175175, LOC103348180, LOC108176660, and LOC108176465 are identified as the pivotal players in the early formed clots on the nano-scaled surfaces. Further bioinformatic prediction indicates that the key LncRNA profiles target the mRNAs related to cell growth and metabolism, bone resorption, and inflammation. The current knowledge demonstrates that in the early stage of osseointegration, surface nano-scaled characteristics of the implants can significantly influence the LncRNA expression in the blood clots, which affects the immune responses, angiogenesis, and osteogenesis through modulating the transcription of targeted mRNAs involved in multiple signaling pathways. The introduction of this chapter paves a way for better interpreting the link between the properties of a blood clot formed on the nano-surface and new bone formation and presents a reference for understanding LncRNAs in biomaterial development for osteointegration.

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References

  • Ahmad S, Hewett PW, Wang P, Al-Ani B, Cudmore M, Fujisawa T, Haigh JJ, Le Noble F, Wang L, Mukhopadhyay D, Ahmed A (2006) Direct evidence for endothelial vascular endothelial growth factor receptor-1 function in nitric oxide-mediated angiogenesis. Circ Res 99(7):715–722

    Article  CAS  Google Scholar 

  • Amaral PP, Mattick JS (2008) Noncoding RNA in development. Mamm Genome 19(7–8):454–492

    Article  CAS  Google Scholar 

  • Andrae J, Gallini R, Betsholtz C (2008) Role of platelet-derived growth factors in physiology and medicine. Genes Dev 22(10):1276–1312

    Article  CAS  Google Scholar 

  • Anitua E, Sánchez M, Nurden AT, Nurden P, Orive G, Andía I (2006) New insights into and novel applications for platelet-rich fibrin therapies. Trends Biotechnol 24(5):227–234

    Article  CAS  Google Scholar 

  • Ashe HL, Monks J, Wijgerde M, Fraser P, Proudfoot NJ (1997) Intergenic transcription and transinduction of the human β-globin locus. Genes Dev 11(19):2494–2509

    Article  CAS  Google Scholar 

  • Bai L, Du Z, Du J, Yao W, Zhang J, Weng Z, Liu S, Zhao Y, Liu Y, Zhang X, Huang X, Yao X, Crawford R, Hang R, Huang D, Tang B, Xiao Y (2018a) A multifaceted coating on titanium dictates osteoimmunomodulation and osteo/angio-genesis towards ameliorative osseointegration. Biomaterials 162:154–169

    Article  CAS  Google Scholar 

  • Bai L, Liu Y, Du Z, Weng Z, Yao W, Zhang X, Huang X, Yao X, Crawford R, Hang R, Huang D, Tang B, Xiao Y (2018b) Differential effect of hydroxyapatite nano-particle versus nano-rod decorated titanium micro-surface on osseointegration. Acta Biomater 76:344–358

    Article  CAS  Google Scholar 

  • Bai L, Yang Y, Mendhi J, Du Z, Hao R, Hang R, Yao X, Huang N, Tang B, Xiao Y (2018c) The effects of TiO2 nanotube arrays with different diameters on macrophage/endothelial cell response and ex vivo hemocompatibility. J Mater Chem B 6(39):6322–6333

    Article  CAS  Google Scholar 

  • Bai L, Chen P, Tang B, Hang R, Xiao Y (2021a) Correlation between LncRNA Profiles in the blood clot formed on nano-scaled implant surfaces and osseointegration. Nanomaterials 11(3):674

    Article  CAS  Google Scholar 

  • Bai L, Zhao Y, Chen P, Zhang X, Huang X, Du Z, Crawford R, Yao X, Tang B, Hang R, Xiao Y (2021b) Targeting early healing phase with titania nanotube arrays on tunable diameters to accelerate bone regeneration and osseointegration. Small 17(4):2006287

    Article  CAS  Google Scholar 

  • Baron R, Kneissel M (2013) WNT signaling in bone homeostasis and disease: from human mutations to treatments. Nat Med 19(2):179–192

    Article  CAS  Google Scholar 

  • Beltran M, Puig I, Peña C, García JM, Alvarez AB, Peña R, Bonilla F, de Herreros AG (2008) A natural antisense transcript regulates Zeb2/Sip1 gene expression during Snail1-induced epithelial-mesenchymal transition. Genes Dev 22(6):756–769

    Article  CAS  Google Scholar 

  • Blair P, Flaumenhaft R (2009) Platelet α-granules: basic biology and clinical correlates. Blood Rev 23(4):177–189

    Article  CAS  Google Scholar 

  • Boyle WJ, Simonet WS, Lacey DL (2003) Osteoclast differentiation and activation. Nature 423(6937):337–342

    Article  CAS  Google Scholar 

  • Browder T, Folkman J, Pirie-Shepherd S (2000) The hemostatic system as a regulator of angiogenesis. J Biol Chem 275(3):1521–1524

    Article  CAS  Google Scholar 

  • Burkhardt MA, Gerber I, Moshfegh C, Lucas MS, Waser J, Emmert MY, Hoerstrup SP, Schlottig F, Vogel V (2017) Clot-entrapped blood cells in synergy with human mesenchymal stem cells create a pro-angiogenic healing response. Biomater Sci 5(10):2009–2023

    Article  CAS  Google Scholar 

  • Chan LW, White NJ, Pun SH (2015) Synthetic strategies for engineering intravenous hemostats. Bioconjug Chem 26(7):1224–1236

    Article  CAS  Google Scholar 

  • Chang J, Wang Z, Tang E, Fan Z, McCauley L, Franceschi R, Guan K, Krebsbach PH, Wang C-Y (2009) Inhibition of osteoblastic bone formation by nuclear factor-κB. Nat Med 15(6):682–689

    Article  CAS  Google Scholar 

  • Chen Z, Klein T, Murray RZ, Crawford R, Chang J, Wu C, Xiao Y (2016) Osteoimmunomodulation for the development of advanced bone biomaterials. Mater Today 19(6):304–321

    Article  CAS  Google Scholar 

  • Chen Z, Bachhuka A, Wei F, Wang X, Liu G, Vasilev K, Xiao Y (2017) Nanotopography-based strategy for the precise manipulation of osteoimmunomodulation in bone regeneration. Nanoscale 9(46):18129–18152

    Article  CAS  Google Scholar 

  • Chu W-M (2013) Tumor necrosis factor. Cancer Lett 328(2):222–225

    Article  CAS  Google Scholar 

  • Davie JE (2003) Understanding peri-implant endosseous healing. J Dent Educ 67(8):932–949

    Article  Google Scholar 

  • Dole NS, Mazur CM, Acevedo C, Lopez JP, Monteiro DA, Fowler TW, Gludovatz B, Walsh F, Regan JN, Messina S, Evans DS, Lang TF, Zhang B, Ritchie RO, Mohammad KS, Alliston T (2017) Osteocyte-intrinsic TGF-β signaling regulates bone quality through perilacunar/canalicular remodeling. Cell Rep 21(9):2585–2596

    Article  CAS  Google Scholar 

  • Du X, Plow EF, Frelinger AL III, O’Toole TE, Loftus JC, Ginsberg MH (1991) Ligands “activate” integrin αIIbβ3 (platelet GPIIb-IIIa). Cell 65(3):409–416

    Article  CAS  Google Scholar 

  • Eming SA, Krieg T, Davidson JM (2007) Inflammation in wound repair: molecular and cellular mechanisms. J Investig Dermatol 127(3):514–525

    Article  CAS  Google Scholar 

  • Feng J, Bi C, Clark BS, Mady R, Shah P, Kohtz JD (2006) The Evf-2 noncoding RNA is transcribed from the Dlx-5/6 ultraconserved region and functions as a Dlx-2 transcriptional coactivator. Genes Dev 20(11):1470–1484

    Article  CAS  Google Scholar 

  • Ferrara N, Gerber H-P, LeCouter J (2003) The biology of VEGF and its receptor. Nat Med 9(6):669–676

    Article  CAS  Google Scholar 

  • Guenther MG, Levine SS, Boyer LA, Jaenisch R, Young RA (2007) A chromatin landmark and transcription initiation at most promoters in human cells. Cell 130(1):77–88

    Article  CAS  Google Scholar 

  • Gurtner GC, Werner S, Barrandon Y, Longaker MT (2008) Wound repair and regeneration. Nature 453(7193):314–321

    Article  CAS  Google Scholar 

  • He Y, Vogelstein B, Velculescu VE, Papadopoulos N, Kinzle KW (2008) The antisense transcriptomes of human cells. Science 322(5909):1855–1857

    Article  CAS  Google Scholar 

  • Herter JM, Rossaint J, Zarbock A (2014) Platelets in inflammation and immunity. J Thromb Haemost 12(11):1764–1775

    Article  CAS  Google Scholar 

  • Kapranov P, Cheng J, Dike S, Nix DA, Duttagupta R, Willingham AT, Stadler PF, Hertel J, Hackermüller J, Hofacker IL, Bell I, Cheung E, Drenkow J, Dumais E, Patel S, Helt G, Ganesh M, Ghosh S, Piccolboni A, Sementchenko V, Tammana H, Gingeras TR (2007) RNA maps reveal new RNA classes and a possible function for pervasive transcription. Science 316(5830):1484–1488

    Article  CAS  Google Scholar 

  • Kim E-S, Kim J-J, Park E-J (2010) Angiogenic factor-enriched platelet-rich plasma enhances in vivo bone formation around alloplastic graft material. J Adv Prosthodont 2(1):7–13

    Article  Google Scholar 

  • Kolar P, Schmidt-Bleek K, Schell H, Gaber T, Toben D, Schmidmaier G, Perka C, Buttgereit F, Duda GN (2010) The early fracture hematoma and its potential role in fracture healing. Tissue Eng Part B Rev 16(4):427–434

    Article  Google Scholar 

  • Krum SA, Chang J, Miranda-Carboni G, Wang C-Y (2010) Novel functions for NFκB: inhibition of bone formation. Nat Rev Rheumatol 6(10):607–611

    Article  CAS  Google Scholar 

  • Listgarten MA, Lang NP, Schroeder HE, Schroeder A (1991) Periodontal tissues and their counterparts around endosseous implants. Clin Oral Implants Res 2(1):1–19

    Article  CAS  Google Scholar 

  • Marco F, Milena F, Gianluca G, Vittoria O (2005) Peri-implant osteogenesis in health and osteoporosis. Micron 36(7–8):630–644

    Article  CAS  Google Scholar 

  • Martianov I, Ramadass A, Barros AS, Chow N, Akoulitchev A (2007) Repression of the human dihydrofolate reductase gene by a non-coding interfering transcript. Nature 445(7128):666–670

    Article  CAS  Google Scholar 

  • Mercer TR, Dinger ME, Mattick JS (2009) Long non-coding RNAs: insights into functions. Nat Rev Genet 10(3):155–159

    Article  CAS  Google Scholar 

  • Miron RJ, Bosshardt DD (2016) OsteoMacs: key players around bone biomaterials. Biomaterials 82:1–19

    Article  CAS  Google Scholar 

  • Nagy JA, Benjamin L, Zeng H, Dvorak AM, Dvorak HF (2008) Vascular permeability, vascular hyperpermeability and angiogenesis. Angiogenesis 11(2):109–119

    Article  CAS  Google Scholar 

  • Nurden AT, Nurden P, Sanchez M, Andia I, Anitua E (2008) Platelets and wound healing. Front Biosci 13(9):3532–3548

    Google Scholar 

  • Oryan A, Alidadi S, Moshiri A (2013) Current concerns regarding healing of bone defects. Hard Tissue 2(2):1–12

    Article  Google Scholar 

  • Park JH, Lee NK, Lee SY (2017) Current understanding of RANK signaling in osteoclast differentiation and maturation. Mol Cells 40(10):706–713

    CAS  Google Scholar 

  • Rinn JL, Kertesz M, Wang JK, Squazzo SL, Xu X, Brugmann SA, Goodnough LH, Helms JA, Farnham PJ, Segal E, Chang HY (2007) Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs. Cell 129(7):1311–1323

    Article  CAS  Google Scholar 

  • Roy SC, Paulose M, Grimes CA (2007) The effect of TiO2 nanotubes in the enhancement of blood clotting for the control of hemorrhage. Biomaterials 28(31):4667–4672

    Article  CAS  Google Scholar 

  • Shahneh F, Grill A, Klein M, Frauhammer F, Bopp T, Schäfer K, Raker VK, Becker C (2021) Specialized regulatory T cells control venous blood clot resolution through SPARC. Blood 137(11):1517–1526

    Article  CAS  Google Scholar 

  • Sivaraman B, Latour RA (2011) Delineating the roles of the GPIIb/IIIa and GP-Ib-IX-V platelet receptors in mediating platelet adhesion to adsorbed fibrinogen and albumin. Biomaterials 32(23):5365–5370

    Article  CAS  Google Scholar 

  • Statello L, Guo C-J, Chen L-L, Huarte M (2020) Gene regulation by long non-coding RNAs and its biological functions. Nat Rev Mol Cell Biol 22(2):96–118

    Article  Google Scholar 

  • Wang KC, Chang HY (2011) Molecular mechanisms of long noncoding RNAs. Mol Cell 43(6):904–914

    Article  CAS  Google Scholar 

  • Wang X, Arai S, Song X, Reichart D, Du K, Pascual G, Tempst P, Rosenfeld MG, Glass CK, Kurokawa R (2008) Induced ncRNAs allosterically modify RNA-binding proteins in cis to inhibit transcription. Nature 454(7200):126–130

    Article  CAS  Google Scholar 

  • Wang Y, Zhang Y, Miron RJ (2016) Health, maintenance, and recovery of soft tissues around implants. Clin Implant Dent Relat Res 18(3):618–634

    Article  Google Scholar 

  • Wapinski O, Chang HY (2011) Long noncoding RNAs and human disease. Trends Cell Biol 21(6):354–361

    Article  CAS  Google Scholar 

  • Willingham AT, Orth AP, Batalov S, Peters EC, Wen BG, Aza-Blanc P, Hogenesch JB, Schultz PG (2005) A strategy for probing the function of noncoding RNAs finds a repressor of NFAT. Science 309(5740):1570–1573

    Article  CAS  Google Scholar 

  • Witham J, Ouboussad L, Lefevre PF (2013) A NF-κB-dependent dual promoter-enhancer initiates the lipopolysaccharide-mediated transcriptional activation of the chicken lysozyme in macrophages. PLoS One 8(3):e59389

    Article  CAS  Google Scholar 

  • Yang J, Zhou Y, Wei F, Xiao Y (2016) Blood clot formed on rough titanium surface induces early cell recruitment. Clin Oral Implants Res 27(8):1031–1038

    Article  Google Scholar 

  • Yao Y, Liu Q, Adrianto I, Wu X, Glassbrook J, Khalasawi N, Yin C, Yi Q, Dong Z, Geissmann F, Zhou L, Mi Q-S (2020) Histone deacetylase 3 controls lung alveolar macrophage development and homeostasis. Nat Commun 11(1):1–15

    Article  Google Scholar 

  • Zarb GA, Koka S (2012) Osseointegration: promise and platitudes. Int J Prosthodont 25(1):11

    Google Scholar 

  • Zhao B (2017) TNF and bone remodeling. Curr Osteoporos Rep 15(3):126–134

    Article  Google Scholar 

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Zhao, Y., Bai, L., Yao, X., Hang, R., Xiao, Y. (2023). Understanding LncRNAs in Biomaterials Development for Osteointegration. In: Chakravorty, N., Shukla, P.C. (eds) Regenerative Medicine. Springer, Singapore. https://doi.org/10.1007/978-981-19-6008-6_13

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