Reduction of Osx expression in the osseointegration process of dental implants with human adipose-derived mesenchymal stem cell intervention: an experimental study

Arif Rachman; Arfiyanti Arfiyanti; Muhammad Dimas Reza Rahmana

doi:10.24198/pjd.vol37no2.62084

Reduction of Osx expression in the osseointegration process of dental implants with human adipose-derived mesenchymal stem cell intervention: an experimental study

Arif Rachman, Arfiyanti Arfiyanti, Muhammad Dimas Reza Rahmana

Abstract

Introduction: Peri-implantitis, an inflammatory response affecting the hard and soft tissues surrounding a dental implant, ultimately leads to a loss of osseointegration. Human adipose-derived mesenchymal stem cells (hADMSCs), sourced from adipose tissue, have high biocompatibility and regenerative capacity, with advantages such as self-renewal, plasticity, and multilineage differentiation. Alveolar bone repair using hADMSC has been demonstrated in periodontitis animal models through the STRO-1, RUNX-2, Osx (Osterix), and COL-I pathways. This study utilized hADMSC intervention to analyze Osx’s impact on the osteointegration process of Y-TZP. Methods: This experimental study employed Wistar rats, divided into six treatment groups (three for Week 1 and three for Week 8) and one negative control group. The study design was a Randomized Post-Test Only Control Group. After Y-TZP scaffold implantation for one and eight weeks, histological analysis identified Osx expression on the mandibular bone surface of Rattus norvegicus albinus Wistar strain rats. Immunohistochemistry (IHC) results for Osx expression were compared using a One-Way ANOVA test for data analysis. Results: Isolation and characterization confirmed that the mesenchymal stem cells were indeed adipose-derived (hADMSCs). A decrease in Osx expression was observed during osteoblast formation, indicating differing mechanisms of action. There was significant inhibition of hADMSC migration, suggesting that homing had occurred (One-Way ANOVA test). Conclusion: Intervention with hADMSCs in Y-TZP dental implants can potentially overcome dental implant failure, as evidenced by a decrease in Osterix expression during osseointegration. This decreased Osterix expression facilitates osteoblast formation and promotes the homing of hADMSCs.

Keywords

Osx expression, hADMSC, osteointegration, dental, implants

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References

Kino S, Tamada Y, Takeuchi K, Nakagomi A, Shiba K, Kusama T, et al. Exploring the relationship between oral health and multiple health conditions: An outcome-wide approach. J Prosthodont Res. 2024;68(3):415–24. https://doi.org/10.2186/jpr.JPR_D_23_00091

Sun AR, Sun Q, Wang Y, Hu L, Wu Y, Ma F, et al. Surface modifications of titanium dental implants with strontium eucommia ulmoides to enhance osseointegration and suppress inflammation. Biomater Res. 2023;27(1):1–13. https://doi.org/10.1186/s40824-023-00361-2

Scannapieco FA, Gershovich E. The prevention of periodontal disease—An overview. Periodontol 2000. 2020;84(1):9–13. https://doi.org/10.1111/prd.12330

Qian SJ, Liu B, Shi J, Zhang X, Deng K, Shen J, et al. Effects of Dental Implants and Nutrition on Elderly Edentulous Subjects: Protocol for a Factorial Randomized Clinical Trial. Front Nutr. 2022;9(June):1–11. https://doi.org/10.3389/fnut.2022.930023

Trivedi A, Trivedi S, Narang H, Sarkar P, Sehdev B, Pendyala G, et al. Evaluation of Pre and Post-loading Peri-implant Crestal Bone Levels Using Cone-beam Computed Tomography: An In Vivo Study. J Contemp Dent Pract. 2022;23(1):79–82. https://doi.org/10.3389/fnut.2022.930023

Cimões R, Pinho RCM, Gurgel BCDV, Borges SB, Júnior EM, Marcantonio CC, et al. Impact of tooth loss due to periodontal disease on the prognosis of rehabilitation. Braz Oral Res. 2021;35(Supplement 2):1–15. https://doi.org/10.1590/1807-3107bor-2021.vol35.0101

Kheder W, Bouzid A, Venkatachalam T, Talaat IM, Elemam NM, Raju TK, et al. Titanium Particles Modulate Lymphocyte and Macrophage Polarization in Peri-Implant Gingival Tissues. Int J Mol Sci. 2023;24(14). https://doi.org/10.3390/ijms241411644

Ramanauskaite A, Becker K, Wolfart S, Lukman F, Schwarz F. Efficacy of rehabilitation with different approaches of implant-supported full-arch prosthetic designs: A systematic review. J Clin Periodontol. 2022;49(S24):272–90. https://doi.org/10.1111/jcpe.13540

Tabrizi R, Zarchini R, Ozkan BT, Majdi S. Dental Implant Survival after Postoperative Infection. J Maxillofac Oral Surg [Internet]. 2022;21(3):796–801. Available from: https://doi.org/10.1007/s12663-020-01460-6

Nguyen TTH, Eo MY, Seo MH, Kim SM. Analysis of acute sinusitis-related early failed implant surface: a combined histological, electron microscopy, and X-ray spectroscopy approach. Maxillofac Plast Reconstr Surg [Internet]. 2022;44(1). Available from: https://doi.org/10.1186/s40902-022-00346-6

Al-Mortadi N, Bataineh K, Albakri I. A Three – Dimensional Finite Element Analysis of Polyetheretherketone PEEK in Dental Implant Prosthesis: A Novel Implant System. Open Dent J. 2022;16(1):1–10. https://doi.org/10.2174/18742106-v16-e2203040

Malm MO, Jemt T, Stenport VF. Patient factors related to early implant failures in the edentulous jaw: A large retrospective case–control study. Clin Implant Dent Relat Res. 2021;23(3):466–76. https://doi.org/10.1111/cid.13009

Tang L, Zhou H, Chen D, Xiang R, Tang J. Weighted Gene Coexpression Network Analysis Identified IL2/STAT5 Signaling Pathway as an Important Determinant of Peri-Implantitis. Comput Math Methods Med. 2022;2022. https://doi.org/10.1155/2022/4202823

Radović M, Gavić L, Jerković D, Željezić D, Puizina J, Srzentić I, et al. Clinical Prospective Assessment of Genotoxic Effects of Dental Implants in Gingival Epithelial Cells. Acta Stomatol Croat. 2022;56(3):222–34. https://doi.org/10.15644/asc56/3/1

Zhang Q, Guo S, Li Y, Li Z, Wang D, Zhang K. Analysis of risk indicators for implant failure in patients with chronic periodontitis. BMC Oral Health. 2024;24(1). https://doi.org/10.1186/s12903-024-04806-5

Song L, Feng Z, Zhou Q, Wu X, Zhang L, Sun Y, et al. Metagenomic analysis of healthy and diseased peri-implant microbiome under different periodontal conditions: a cross-sectional study. BMC Oral Health. 2024;24(1):1–17. https://doi.org/10.1186/s12903-023-03442-9

Pigossi SC, Alvim-Pereira F, Montes CC, Finoti LS, Secolin R, Trevilatto PC, et al. Genetic association study between Interleukin 10 gene and dental implant loss. Arch Oral Biol. 2012;57(9):1256–63. https://doi.org/10.1016/j.archoralbio.2012.02.020

Matthes R, Jablonowski L, Miebach L, Pitchika V, Holtfreter B, Eberhard C, et al. In-Vitro Biofilm Removal Efficacy Using Water Jet in Combination with Cold Plasma Technology on Dental Titanium Implants. Int J Mol Sci. 2023;24(2). https://doi.org/10.3390/ijms24021606

Ding Z, Peng Q, Zuo J, Wang Y, Zhou H, Tang Z. Osteogenesis Performance of Boronized Ti6Al4V/HA Composites Prepared by Microwave Sintering: In Vitro and In Vivo Studies. Materials (Basel). 2022;15(14). https://doi.org/10.3390/ma15144985

Liu X, Deng S, Xie J, Xu C, Huang Z, Huang B, et al. 2-DG Regulates Immune Imbalance on the Titanium Surface after Debridement. Int J Mol Sci. 2023;24(14):1–15. https://doi.org/10.3390/ijms241411431

Bhattacharjee A, Pereira B, Soares P, Popat KC. Titania (TiO2) nanotube surfaces doped with zinc and strontium for improved cell compatibility. Nanoscale. 2024;16(26):12510–22. https://doi.org/10.1039/D4NR01123F

Santamaría Arrieta G, Rodríguez Sánchez F, Rodriguez-Andrés C, Barbier L, Arteagoitia I. The effect of preoperative clindamycin in reducing early oral implant failure: a randomised placebo-controlled clinical trial. Clin Oral Investig. 2023;27(3):1113–22. https://doi.org/10.1007/s00784-022-04701-9

Hadady H, Alam A, Khurana I, Mutreja I, Kumar D, Shankar MR, et al. Optimizing alkaline hydrothermal treatment for biomimetic smart metallic orthopedic and dental implants. J Mater Sci Mater Med. 2024;35(1). https://doi.org/10.1007/s10856-024-06794-y

Kang MK, Lee SB, Moon SK, Kim KM, Kim KN. The biomimetic apatite-cefalotin coatings on modifed titanium. Dent Mater J. 2012;31(1):98–105. https://doi.org/10.4012/dmj.2011-131

Pizarek JA, Fischer NG, Aparicio C. Immunomodulatory IL-23 receptor antagonist peptide nanocoatings for implant soft tissue healing. Dent Mater. 2023;39(2):204–16. https://doi.org/10.1016/j.dental.2023.01.001

Tambone E, Bonomi E, Ghensi P, Maniglio D, Ceresa C, Agostinacchio F, et al. Rhamnolipid coating reduces microbial biofilm formation on titanium implants: an in vitro study. BMC Oral Health [Internet]. 2021;21(1):1–13. Available from: https://doi.org/10.1186/s12903-021-01412-7

Huang P, Chen X, Chen Z, Chen M, He J, Peng L. Efficacy of Er:YAG laser irradiation for decontamination and its effect on biocompatibility of different titanium surfaces. BMC Oral Health [Internet]. 2021;21(1):1–12. Available from: https://doi.org/10.1186/s12903-021-02006-z

Korsch M, Marten SM, Stoll D, Prechtl C, Dötsch A. Microbiological findings in early and late implant loss: an observational clinical case-controlled study. BMC Oral Health [Internet]. 2021;21(1):1–11. Available from: https://doi.org/10.1186/s12903-021-01439-w

Yao L, Al-Bishari AM, Shen J, Wang Z, Liu T, Sheng L, et al. Osseointegration and anti-infection of dental implant under osteoporotic conditions promoted by gallium oxide nano-layer coated titanium dioxide nanotube arrays. Ceram Int [Internet]. 2023;49(14):22961–9. Available from: https://doi.org/10.1016/j.ceramint.2023.04.121

do Nascimento M, Brito TO, Lima AM, Elias CN. Protein interactions with osseointegrable titanium implants. Brazilian J Oral Sci. 2022;22:1–15. https://doi.org/10.20396/bjos.v22i00.8668749

Sandra Sari D, Martin M, Maduratna E, Basuki Notobroto H, Mahyudin F, Sudiana K, et al. Combination adipose-derived mesenchymal stem cells-demineralized dentin matrix increase bone marker expression in periodontitis rats. Saudi Dent J [Internet]. 2023;35(8):960–8. Available from: https://doi.org/10.1016/j.sdentj.2023.07.019

Tan X, Zhao Y, Lu Y, Yu P, Mei Z, Yu H. Physical and biological implications of accelerated aging on stereolithographic additive-manufactured zirconia for dental implant abutment. J Prosthodont Res. 2022;66(4):600–9. https://doi.org/10.2186/jpr.JPR_D_21_00240

Wang B, Xie X, Jiang W, Zhan Y, Zhang Y, Guo Y, et al. Osteoinductive micro-nano guided bone regeneration membrane for in situ bone defect repair. Stem Cell Res Ther. 2024;15(1):1–15. https://doi.org/10.1186/s13287-024-03745-w

Kollek NJ, Pérez-Albacete Martínez C, Granero Marín JM, Maté Sánchez De Val JE. Prospective Clinical Study with New Materials for Tissue Regeneration: A Study in Humans. Eur J Dent. 2022; https://doi.org/10.1055/s-0042-1753453

Grassi A, Monica D, Minetti E, Ballini A, Gianfreda F, Bollero P, et al. Innovative Alveolar Ridge Preservation Surgical Technique with Immediate Dental Implant Placement: A Retrospective Case Report of 1-Year Follow-Up. Eur J Dent. 2024;18(1):408–14. https://doi.org/10.1055/s-0043-1772676

Fayed O, Van Griensven M, Tahmasebi Birgani Z, Plank C, Balmayor ER. Transcript-Activated Coatings on Titanium Mediate Cellular Osteogenesis for Enhanced Osteointegration. Mol Pharm. 2021;18(3):1121–37. https://doi.org/10.1021/acs.molpharmaceut.0c01042

Garcia Gómez-Heras S, Garcia-Arranz M, Vega-Clemente L, Olivera-Salazar R, Vélez Pinto JF, Fernández-García M, et al. Study of the Effect of Wild-Type and Transiently Expressing CXCR4 and IL-10 Mesenchymal Stromal Cells in a Mouse Model of Peritonitis. Int J Mol Sci. 2024;25(1). https://doi.org/10.3390/ijms25010520

Tribst JPM, de Morais DC, de Matos JDM, Lopes G da RS, Dal Piva AM de O, Borges ALS, et al. Influence of Framework Material and Posterior Implant Angulation in Full-Arch All-on-4 Implant-Supported Prosthesis Stress Concentration. Dent J. 2022;10(1). https://doi.org/10.3390/dj10010012

Elraggal A, Abdelraheem IM, Watts DC, Roy S, Dommeti VK, Alshabib A, et al. Biomechanical reinforcement by CAD-CAM materials affects stress distributions of posterior composite bridges: 3D finite element analysis. Dent Mater [Internet]. 2024;40(5):869–77. Available from: https://doi.org/10.1016/j.dental.2024.04.001

Souza ILM, Suzukawa AA, Josino R, Marcon BH, Robert AW, Shigunov P, et al. Cellular In Vitro Responses Induced by Human Mesenchymal Stem/Stromal Cell-Derived Extracellular Vesicles Obtained from Suspension Culture. Int J Mol Sci. 2024;25(14). https://doi.org/10.3390/ijms25147605

Kim M, Wang X, Li Y, Lin Z, Collins CP, Liu Y, et al. Personalized composite scaffolds for accelerated cell- and growth factor-free craniofacial bone regeneration. Bioact Mater [Internet]. 2024;41(January):427–39. Available from: https://doi.org/10.1016/j.bioactmat.2024.07.029

Abdollahi A, Aghayan HR, Mousivand Z, Motasadizadeh H, Maghsoudian S, Abdorashidi M, et al. Chitosan based extruded nanofibrous bioscaffold for local delivery of mesenchymal stem cells to improve diabetic wound healing. Stem Cell Res Ther [Internet]. 2024;15(1). Available from: https://doi.org/10.1186/s13287-024-03772-7

Fazal N, Khawaja H, Naseer N, Khan AJ, Latief N. Daphne mucronata enhances cell proliferation and protects human adipose stem cells against monosodium iodoacetate induced oxidative stress in vitro. Adipocyte [Internet]. 2020;9(1):495–508. Available from: https://doi.org/10.1080/21623945.2020.1812242

Andrique C, Bonnet AL, Dang J, Lesieur J, Krautzberger AM, Baroukh B, et al. Vasorin as an actor of bone turnover? J Cell Physiol. 2024;239(6). https://doi.org/10.1002/jcp.31257

Sabatelli S, Scarpa ES, Giuliani A, Giordani C, Sabbatinelli J, Rippo MR, et al. Pro-Osteogenic Effect of the Nutraceutical BlastiMin Complex® in Women with Osteoporosis or Osteopenia: An Open Intervention Clinical Trial. Int J Mol Sci. 2024;25(16). https://doi.org/10.3390/ijms25168565

Cao Y, Boss AL, Bolam SM, Munro JT, Crawford H, Dalbeth N, et al. In Vitro Cell Surface Marker Expression on Mesenchymal Stem Cell Cultures does not Reflect Their Ex Vivo Phenotype. Stem Cell Rev Reports. 2024;1656–66. https://doi.org/10.1007/s12015-024-10743-1

Huang C, Shi S, Qin M, Rong X, Ding Z, Fu X, et al. A Composite Hydrogel Functionalized by Borosilicate Bioactive Glasses and VEGF for Critical-Size Bone Regeneration. Adv Sci. 2024;11(26):1–18. https://doi.org/10.1002/advs.202400349

Wei L, Wu S, Kuss M, Jiang X, Sun R, Reid P, et al. 3D printing of silk fibroin-based hybrid scaffold treated with platelet rich plasma for bone tissue engineering. Bioact Mater. 2019;4(July 2019):256–60. https://doi.org/10.1016/j.bioactmat.2019.09.001

Dewey MJ, Nosatov A V., Subedi K, Shah R, Jakus A, Harley BAC. Inclusion of a 3D-printed Hyperelastic Bone mesh improves mechanical and osteogenic performance of a mineralized collagen scaffold. Acta Biomater [Internet]. 2021;121:224–36. Available from: https://doi.org/10.1016/j.actbio.2020.11.028

Saalbach A, Stein M, Lee S, Krügel U, Haffner-Luntzer M, Krohn K, et al. Bone quality relies on hyaluronan synthesis – Insights from mice with complete knockout of hyaluronan synthase expression. Matrix Biol Plus [Internet]. 2024;24(August):100163. Available from: https://doi.org/10.1016/j.mbplus.2024.100163

Wagener N, Lehmann W, Weiser L, Jäckle K, Di Fazio P, Schilling AF, et al. Psychostimulants Modafinil, Atomoxetine and Guanfacine Impair Bone Cell Differentiation and MSC Migration. Int J Mol Sci. 2022;23(18). https://doi.org/10.3390/ijms231810257

Subu Taopan HHM, Annisa Dewi FN, Mariya S, Darusman H, Permanawati P, Sajuthi D, et al. CHARACTERIZATION OF MESENCHYMAL STEM CELLS FROM WHITE ADIPOSE TISSUE OF Macaca fascicularis. J Kedokt Hewan - Indones J Vet Sci. 2021;15(4):112–7. Available from: https://doi.org/10.21157/j.ked.hewan.v15i4.18203

DOI: https://doi.org/10.24198/pjd.vol37no2.62084