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
Amaral PP, Mattick JS (2008) Noncoding RNA in development. Mamm Genome 19(7–8):454–492
Andrae J, Gallini R, Betsholtz C (2008) Role of platelet-derived growth factors in physiology and medicine. Genes Dev 22(10):1276–1312
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
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
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
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
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
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
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
Baron R, Kneissel M (2013) WNT signaling in bone homeostasis and disease: from human mutations to treatments. Nat Med 19(2):179–192
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
Blair P, Flaumenhaft R (2009) Platelet α-granules: basic biology and clinical correlates. Blood Rev 23(4):177–189
Boyle WJ, Simonet WS, Lacey DL (2003) Osteoclast differentiation and activation. Nature 423(6937):337–342
Browder T, Folkman J, Pirie-Shepherd S (2000) The hemostatic system as a regulator of angiogenesis. J Biol Chem 275(3):1521–1524
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
Chan LW, White NJ, Pun SH (2015) Synthetic strategies for engineering intravenous hemostats. Bioconjug Chem 26(7):1224–1236
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
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
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
Chu W-M (2013) Tumor necrosis factor. Cancer Lett 328(2):222–225
Davie JE (2003) Understanding peri-implant endosseous healing. J Dent Educ 67(8):932–949
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
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
Eming SA, Krieg T, Davidson JM (2007) Inflammation in wound repair: molecular and cellular mechanisms. J Investig Dermatol 127(3):514–525
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
Ferrara N, Gerber H-P, LeCouter J (2003) The biology of VEGF and its receptor. Nat Med 9(6):669–676
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
Gurtner GC, Werner S, Barrandon Y, Longaker MT (2008) Wound repair and regeneration. Nature 453(7193):314–321
He Y, Vogelstein B, Velculescu VE, Papadopoulos N, Kinzle KW (2008) The antisense transcriptomes of human cells. Science 322(5909):1855–1857
Herter JM, Rossaint J, Zarbock A (2014) Platelets in inflammation and immunity. J Thromb Haemost 12(11):1764–1775
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
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
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
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
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
Marco F, Milena F, Gianluca G, Vittoria O (2005) Peri-implant osteogenesis in health and osteoporosis. Micron 36(7–8):630–644
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
Mercer TR, Dinger ME, Mattick JS (2009) Long non-coding RNAs: insights into functions. Nat Rev Genet 10(3):155–159
Miron RJ, Bosshardt DD (2016) OsteoMacs: key players around bone biomaterials. Biomaterials 82:1–19
Nagy JA, Benjamin L, Zeng H, Dvorak AM, Dvorak HF (2008) Vascular permeability, vascular hyperpermeability and angiogenesis. Angiogenesis 11(2):109–119
Nurden AT, Nurden P, Sanchez M, Andia I, Anitua E (2008) Platelets and wound healing. Front Biosci 13(9):3532–3548
Oryan A, Alidadi S, Moshiri A (2013) Current concerns regarding healing of bone defects. Hard Tissue 2(2):1–12
Park JH, Lee NK, Lee SY (2017) Current understanding of RANK signaling in osteoclast differentiation and maturation. Mol Cells 40(10):706–713
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
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
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
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
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
Wang KC, Chang HY (2011) Molecular mechanisms of long noncoding RNAs. Mol Cell 43(6):904–914
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
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
Wapinski O, Chang HY (2011) Long noncoding RNAs and human disease. Trends Cell Biol 21(6):354–361
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
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
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
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
Zarb GA, Koka S (2012) Osseointegration: promise and platitudes. Int J Prosthodont 25(1):11
Zhao B (2017) TNF and bone remodeling. Curr Osteoporos Rep 15(3):126–134
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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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