Research Article
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EFFECT OF TIDEGLUSIB WITH BONE GRAFTING ON NEW BONE FORMATION

Year 2021, Volume: 24 Issue: 3, 224 - 231, 15.09.2021

Berrin İyilikci , Ufuk Taşdemir , Özlem Özmen , Alper Kızıldağ

https://doi.org/10.7126/cumudj.943229

Abstract

ABSTRACT
Objectives: The goal of this study was to observe the regenerative potential of Tideglusib in combination with autogenous and xenograft mandibular defects in rats.
Material Methods: Our study consists of five groups: one control and four experimental. In 40 Wistar albino rats, 5-mm-diameter critical bone defects were created at the angle of the mandible. In the control group, the defect was not filled. The defects were grafted only Xenograft in Group 1, with Xenograft and tideglusib in Group 2, and with only autogenous bone graft in Group3, and with autogenous bone graft mixed with tideglusib in Group 4.
Results: Sterological analyses revealed that enhanced new bone formation in the Group 4 compare to Control and Group 1. Immunohistochemically marked expressions of BMP-2 and VEGF were observed in Group 4.
Conclusions: Our results demonstrated that Tideglusib, in combination with bone grafting has an adjuvant effect on BMP-2 and VEGF-A expressions that may accelerate bone regeneration.

Keywords

Autogenous Bone Graft BMP-2 Bone healing Tideglusib VEGF-A

Supporting Institution

This study was supported by the Scientific Research Project Fund of Pamukkale University

Project Number

Project Number: 2018DİŞF011

References

  • [1] Miron RJ, Zhang Q, Sculean A, Buser D, Pippenger BE, Dard M, et al. Osteoinductive potential of 4 commonly employed bone grafts. Clin Oral Investig 2016;20:2259–65. https://doi.org/10.1007/s00784-016-1724-4.
  • [2] Wang W, Yeung KWK. Bone grafts and biomaterials substitutes for bone defect repair: A review. Bioact Mater 2017;2:224–47. https://doi.org/10.1016/j.bioactmat.2017.05.007.
  • [3] Ruhé PQ, Boerman OC, Russel FGM, Mikos AG, Spauwen PHM, Jansen JA. In vivo release of rhBMP-2 loaded porous calcium phosphate cement pretreated with albumin. J Mater Sci Mater Med 2006;17:919–27. https://doi.org/10.1007/s10856-006-0181-z.
  • [4] Luna-Medina R, Cortes-Canteli M, Sanchez-Galiano S, Morales-Garcia JA, Martinez A, Santos A, et al. NP031112, a thiadiazolidinone compound, prevents inflammation and neurodegeneration under excitotoxic conditions: potential therapeutic role in brain disorders. J Neurosci 2007;27:5766–76. https://doi.org/10.1523/JNEUROSCI.1004-07.2007.
  • [5] Neves VCM, Babb R, Chandrasekaran D, Sharpe PT. Promotion of natural tooth repair by small molecule GSK3 antagonists. Sci Rep 2017;7:1–7. https://doi.org/10.1038/srep39654.
  • [6] Bath-Balogh M, Fehrenbach MJ. Illustrated Dental Embryology, Histology, and Anatomy. Elsevier Health Sciences; 2011.
  • [7] Elsalanty ME, Genecov DG. Bone Grafts in Craniofacial Surgery n.d. https://doi.org/10.1055/s-0029-1215875.
  • [8] Smith MH, Izumi K, Feinberg SE. Chapter 9 - Tissue Engineering. Curr. Ther. Oral Maxillofac. Surg., Elsevier Inc.; n.d., p. 79–91. https://doi.org/10.1016/B978-1-4160-2527-6.00009-8.
  • [9] Rinaldi M, Ganz SD, Mottola A. Computer-Guided Applications for Dental Implants, Bone Grafting, and Reconstructive Surgery. 2015. https://doi.org/10.1016/C2013-0-13012-7.
  • [10] Seyhan N, Keskin S, Aktan M, Avunduk MC, Sengelen M, Savaci N. Comparison of the effect of platelet-rich plasma and simvastatin on healing of critical-size calvarial bone defects. J Craniofac Surg 2016;27:1367–70. https://doi.org/10.1097/SCS.0000000000002728.
  • [11] Alam S, Ueki K, Nakagawa K, Marukawa K, Hashiba Y, Yamamoto E, et al. Statin-induced bone morphogenetic protein (BMP) 2 expression during bone regeneration: an immunohistochemical study. Oral Surgery, Oral Med Oral Pathol Oral Radiol Endodontology 2009;107:22–9. https://doi.org/10.1016/j.tripleo.2008.06.025.
  • [12] Aghajanian P, Hall S, Wongworawat MD, Mohan S. The Roles and Mechanisms of Actions of Vitamin C in Bone: New Developments. J Bone Miner Res 2015;30:1945–55. https://doi.org/10.1002/jbmr.2709.
  • [13] Ilyas A, Odatsu T, Shah A, Monte F, Kim HKW, Kramer P, et al. Amorphous Silica: A New Antioxidant Role for Rapid Critical-Sized Bone Defect Healing. Adv Healthc Mater 2016;5:2199–213. https://doi.org/10.1002/adhm.201600203.
  • [14] Ripamonti U, Heliotis M, Ferretti C. Bone Morphogenetic Proteins and the Induction of Bone Formation: From Laboratory to Patients. Oral Maxillofac Surg Clin North Am 2007;19:575–89. https://doi.org/10.1016/j.coms.2007.07.006.
  • [15] Wikesjö U, Qahash M, Huang Y-H, Xiropaidis A, Polimeni G, Susin C. Bone morphogenetic proteins for periodontal and alveolar indications; biological observations - clinical implications. Orthod Craniofac Res 2009;12:263–70. https://doi.org/10.1111/j.1601-6343.2009.01461.x.
  • [16] Bergwitz C, Wendlandt T, Kispert A, Brabant G. Wnts differentially regulate colony growth and differentiation of chondrogenic rat calvaria cells. Biochim Biophys Acta - Mol Cell Res 2001;1538:129–40. https://doi.org/10.1016/S0167-4889(00)00123-3.
  • [17] Fischer L, Boland G, Tuan RS. Wnt signaling during BMP-2 stimulation of mesenchymal chondrogenesis. J Cell Biochem 2002;84:816–31.
  • [18] Hemmerich A, Brown H, Smith S, Marthndam SSK, Wyss UP. Distinct Roles of Bone Morphogenetic Proteins in Osteogenic Differentiation of Mesenchymal Stem Cells. J Orthop Res 2006;11:770–81. https://doi.org/10.1002/jor.
  • [19] Schnabel M, Fichtel I, Gotzen L, Schlegel J. Differential expression of Notch genes in human osteoblastic cells. Int J Mol Med 2002;9:229–32. https://doi.org/10.3892/ijmm.9.3.229.
  • [20] Hooper JE, Scott MP. Communicating with Hedgehogs. Nat Rev Mol Cell Biol 2005;6:306–17. https://doi.org/10.1038/nrm1622.
  • [21] Ornitz DM, Marie PJ. FGF signaling pathways in endochondral and intramembranous bone development and human genetic disease. Genes Dev 2002;16:1446–65. https://doi.org/10.1101/gad.990702.
  • [22] Holmen SL, Zylstra CR, Mukherjee A, Sigler RE, Faugere MC, Bouxsein ML, et al. Essential role of β-catenin in postnatal bone acquisition. J Biol Chem 2005;280:21162–8. https://doi.org/10.1074/jbc.M501900200.
  • [23] Seitz IA, Teven CM, Reid RR. 21 - Repair and grafting of bone. Plast. Surg. Third Edit, Elsevier Inc.; 2017, p. 425-463.e16. https://doi.org/10.1016/B978-1-4377-1733-4.00121-X.
  • [24] Duan P, Bonewald LF. The role of the wnt/β-catenin signaling pathway in formation and maintenance of bone and teeth. Int J Biochem Cell Biol 2016;77:23–9. https://doi.org/10.1016/j.biocel.2016.05.015.
  • [25] Domínguez JM, Fuertes A, Orozco L, del Monte-Millán M, Delgado E, Medina M. Evidence for irreversible inhibition of glycogen synthase kinase-3β by tideglusib. J Biol Chem 2012;287:893–904. https://doi.org/10.1074/jbc.M111.306472.
  • [26] Arioka M, Takahashi-Yanaga F, Sasaki M, Yoshihara T, Morimoto S, Hirata M, et al. Acceleration of bone regeneration by local application of lithium: Wnt signal-mediated osteoblastogenesis and Wnt signal-independent suppression of osteoclastogenesis. Biochem Pharmacol 2014;90:397–405. https://doi.org/10.1016/j.bcp.2014.06.011.
  • [27] Chen Y, Whetstone HC, Youn A, Nadesan P, Chow ECY, Lin AC, et al. β-Catenin signaling pathway is crucial for bone morphogenetic protein 2 to induce new bone formation. J Biol Chem 2007;282:526–33. https://doi.org/10.1074/jbc.M602700200.
  • [28] Yuan G, Yang G, Zheng Y, Zhu X, Chen Z, Zhang Z, et al. The non-canonical BMP and Wnt/ -catenin signaling pathways orchestrate early tooth development. Development 2015;142:128–39. https://doi.org/10.1242/dev.117887.
  • [29] Zhang F, Song J, Zhang H, Huang E, Song D, Tollemar V, et al. Wnt and BMP signaling crosstalk in regulating dental stem cells: Implications in dental tissue engineering. Genes Dis 2016;3:263–76. https://doi.org/10.1016/j.gendis.2016.09.004.
  • [30] Galli C, Piemontese M, Lumetti S, Manfredi E, Macaluso GM, Passeri G. GSK3b-inhibitor lithium chloride enhances activation of Wnt canonical signaling and osteoblast differentiation on hydrophilic titanium surfaces. Clin Oral Implants Res 2013;24:921–7. https://doi.org/10.1111/j.1600-0501.2012.02488.x.
  • [31] Jin Y, Xu L, Hu X, Liao S, Pathak JL, Liu J. Lithium chloride enhances bone regeneration and implant osseointegration in osteoporotic conditions. J Bone Miner Metab 2017;35:497–503. https://doi.org/10.1007/s00774-016-0783-6.
  • [32] Tai I-C, Fu Y-C, Wang C-K, Chang J-K, Ho M-L. Local delivery of controlled-release simvastatin/PLGA/HAp microspheres enhances bone repair. Int J Nanomedicine 2013;8:3895–904. https://doi.org/10.2147/IJN.S48694.
  • [33] Kawakami Y, Ii M, Matsumoto T, Kawamoto A, Kuroda R, Akimaru H, et al. A small interfering RNA targeting Lnk accelerates bone fracture healing with early neovascularization. Lab Investig 2013;93:1036–53. https://doi.org/10.1038/labinvest.2013.93.
  • [34] Wang T, Guo S, Zhang H. Synergistic Effects of Controlled-Released BMP-2 and VEGF from nHAC/PLGAs Scaffold on Osteogenesis. Biomed Res Int 2018;2018:3516463. https://doi.org/10.1155/2018/3516463.
  • [35] Li P, Bai Y, Yin G, Pu X, Huang Z, Liao X, et al. Synergistic and sequential effects of BMP-2, bFGF and VEGF on osteogenic differentiation of rat osteoblasts. J Bone Miner Metab 2014;32:627–35. https://doi.org/10.1007/s00774-013-0538-6.
  • [36] Bai Y, Li P, Yin G, Huang Z, Liao X, Chen X, et al. BMP-2, VEGF and bFGF synergistically promote the osteogenic differentiation of rat bone marrow-derived mesenchymal stem cells. Biotechnol Lett 2013;35:301–8. https://doi.org/10.1007/s10529-012-1084-3.

Year 2021, Volume: 24 Issue: 3, 224 - 231, 15.09.2021

Berrin İyilikci , Ufuk Taşdemir , Özlem Özmen , Alper Kızıldağ

https://doi.org/10.7126/cumudj.943229

Abstract

Project Number

Project Number: 2018DİŞF011

References

  • [1] Miron RJ, Zhang Q, Sculean A, Buser D, Pippenger BE, Dard M, et al. Osteoinductive potential of 4 commonly employed bone grafts. Clin Oral Investig 2016;20:2259–65. https://doi.org/10.1007/s00784-016-1724-4.
  • [2] Wang W, Yeung KWK. Bone grafts and biomaterials substitutes for bone defect repair: A review. Bioact Mater 2017;2:224–47. https://doi.org/10.1016/j.bioactmat.2017.05.007.
  • [3] Ruhé PQ, Boerman OC, Russel FGM, Mikos AG, Spauwen PHM, Jansen JA. In vivo release of rhBMP-2 loaded porous calcium phosphate cement pretreated with albumin. J Mater Sci Mater Med 2006;17:919–27. https://doi.org/10.1007/s10856-006-0181-z.
  • [4] Luna-Medina R, Cortes-Canteli M, Sanchez-Galiano S, Morales-Garcia JA, Martinez A, Santos A, et al. NP031112, a thiadiazolidinone compound, prevents inflammation and neurodegeneration under excitotoxic conditions: potential therapeutic role in brain disorders. J Neurosci 2007;27:5766–76. https://doi.org/10.1523/JNEUROSCI.1004-07.2007.
  • [5] Neves VCM, Babb R, Chandrasekaran D, Sharpe PT. Promotion of natural tooth repair by small molecule GSK3 antagonists. Sci Rep 2017;7:1–7. https://doi.org/10.1038/srep39654.
  • [6] Bath-Balogh M, Fehrenbach MJ. Illustrated Dental Embryology, Histology, and Anatomy. Elsevier Health Sciences; 2011.
  • [7] Elsalanty ME, Genecov DG. Bone Grafts in Craniofacial Surgery n.d. https://doi.org/10.1055/s-0029-1215875.
  • [8] Smith MH, Izumi K, Feinberg SE. Chapter 9 - Tissue Engineering. Curr. Ther. Oral Maxillofac. Surg., Elsevier Inc.; n.d., p. 79–91. https://doi.org/10.1016/B978-1-4160-2527-6.00009-8.
  • [9] Rinaldi M, Ganz SD, Mottola A. Computer-Guided Applications for Dental Implants, Bone Grafting, and Reconstructive Surgery. 2015. https://doi.org/10.1016/C2013-0-13012-7.
  • [10] Seyhan N, Keskin S, Aktan M, Avunduk MC, Sengelen M, Savaci N. Comparison of the effect of platelet-rich plasma and simvastatin on healing of critical-size calvarial bone defects. J Craniofac Surg 2016;27:1367–70. https://doi.org/10.1097/SCS.0000000000002728.
  • [11] Alam S, Ueki K, Nakagawa K, Marukawa K, Hashiba Y, Yamamoto E, et al. Statin-induced bone morphogenetic protein (BMP) 2 expression during bone regeneration: an immunohistochemical study. Oral Surgery, Oral Med Oral Pathol Oral Radiol Endodontology 2009;107:22–9. https://doi.org/10.1016/j.tripleo.2008.06.025.
  • [12] Aghajanian P, Hall S, Wongworawat MD, Mohan S. The Roles and Mechanisms of Actions of Vitamin C in Bone: New Developments. J Bone Miner Res 2015;30:1945–55. https://doi.org/10.1002/jbmr.2709.
  • [13] Ilyas A, Odatsu T, Shah A, Monte F, Kim HKW, Kramer P, et al. Amorphous Silica: A New Antioxidant Role for Rapid Critical-Sized Bone Defect Healing. Adv Healthc Mater 2016;5:2199–213. https://doi.org/10.1002/adhm.201600203.
  • [14] Ripamonti U, Heliotis M, Ferretti C. Bone Morphogenetic Proteins and the Induction of Bone Formation: From Laboratory to Patients. Oral Maxillofac Surg Clin North Am 2007;19:575–89. https://doi.org/10.1016/j.coms.2007.07.006.
  • [15] Wikesjö U, Qahash M, Huang Y-H, Xiropaidis A, Polimeni G, Susin C. Bone morphogenetic proteins for periodontal and alveolar indications; biological observations - clinical implications. Orthod Craniofac Res 2009;12:263–70. https://doi.org/10.1111/j.1601-6343.2009.01461.x.
  • [16] Bergwitz C, Wendlandt T, Kispert A, Brabant G. Wnts differentially regulate colony growth and differentiation of chondrogenic rat calvaria cells. Biochim Biophys Acta - Mol Cell Res 2001;1538:129–40. https://doi.org/10.1016/S0167-4889(00)00123-3.
  • [17] Fischer L, Boland G, Tuan RS. Wnt signaling during BMP-2 stimulation of mesenchymal chondrogenesis. J Cell Biochem 2002;84:816–31.
  • [18] Hemmerich A, Brown H, Smith S, Marthndam SSK, Wyss UP. Distinct Roles of Bone Morphogenetic Proteins in Osteogenic Differentiation of Mesenchymal Stem Cells. J Orthop Res 2006;11:770–81. https://doi.org/10.1002/jor.
  • [19] Schnabel M, Fichtel I, Gotzen L, Schlegel J. Differential expression of Notch genes in human osteoblastic cells. Int J Mol Med 2002;9:229–32. https://doi.org/10.3892/ijmm.9.3.229.
  • [20] Hooper JE, Scott MP. Communicating with Hedgehogs. Nat Rev Mol Cell Biol 2005;6:306–17. https://doi.org/10.1038/nrm1622.
  • [21] Ornitz DM, Marie PJ. FGF signaling pathways in endochondral and intramembranous bone development and human genetic disease. Genes Dev 2002;16:1446–65. https://doi.org/10.1101/gad.990702.
  • [22] Holmen SL, Zylstra CR, Mukherjee A, Sigler RE, Faugere MC, Bouxsein ML, et al. Essential role of β-catenin in postnatal bone acquisition. J Biol Chem 2005;280:21162–8. https://doi.org/10.1074/jbc.M501900200.
  • [23] Seitz IA, Teven CM, Reid RR. 21 - Repair and grafting of bone. Plast. Surg. Third Edit, Elsevier Inc.; 2017, p. 425-463.e16. https://doi.org/10.1016/B978-1-4377-1733-4.00121-X.
  • [24] Duan P, Bonewald LF. The role of the wnt/β-catenin signaling pathway in formation and maintenance of bone and teeth. Int J Biochem Cell Biol 2016;77:23–9. https://doi.org/10.1016/j.biocel.2016.05.015.
  • [25] Domínguez JM, Fuertes A, Orozco L, del Monte-Millán M, Delgado E, Medina M. Evidence for irreversible inhibition of glycogen synthase kinase-3β by tideglusib. J Biol Chem 2012;287:893–904. https://doi.org/10.1074/jbc.M111.306472.
  • [26] Arioka M, Takahashi-Yanaga F, Sasaki M, Yoshihara T, Morimoto S, Hirata M, et al. Acceleration of bone regeneration by local application of lithium: Wnt signal-mediated osteoblastogenesis and Wnt signal-independent suppression of osteoclastogenesis. Biochem Pharmacol 2014;90:397–405. https://doi.org/10.1016/j.bcp.2014.06.011.
  • [27] Chen Y, Whetstone HC, Youn A, Nadesan P, Chow ECY, Lin AC, et al. β-Catenin signaling pathway is crucial for bone morphogenetic protein 2 to induce new bone formation. J Biol Chem 2007;282:526–33. https://doi.org/10.1074/jbc.M602700200.
  • [28] Yuan G, Yang G, Zheng Y, Zhu X, Chen Z, Zhang Z, et al. The non-canonical BMP and Wnt/ -catenin signaling pathways orchestrate early tooth development. Development 2015;142:128–39. https://doi.org/10.1242/dev.117887.
  • [29] Zhang F, Song J, Zhang H, Huang E, Song D, Tollemar V, et al. Wnt and BMP signaling crosstalk in regulating dental stem cells: Implications in dental tissue engineering. Genes Dis 2016;3:263–76. https://doi.org/10.1016/j.gendis.2016.09.004.
  • [30] Galli C, Piemontese M, Lumetti S, Manfredi E, Macaluso GM, Passeri G. GSK3b-inhibitor lithium chloride enhances activation of Wnt canonical signaling and osteoblast differentiation on hydrophilic titanium surfaces. Clin Oral Implants Res 2013;24:921–7. https://doi.org/10.1111/j.1600-0501.2012.02488.x.
  • [31] Jin Y, Xu L, Hu X, Liao S, Pathak JL, Liu J. Lithium chloride enhances bone regeneration and implant osseointegration in osteoporotic conditions. J Bone Miner Metab 2017;35:497–503. https://doi.org/10.1007/s00774-016-0783-6.
  • [32] Tai I-C, Fu Y-C, Wang C-K, Chang J-K, Ho M-L. Local delivery of controlled-release simvastatin/PLGA/HAp microspheres enhances bone repair. Int J Nanomedicine 2013;8:3895–904. https://doi.org/10.2147/IJN.S48694.
  • [33] Kawakami Y, Ii M, Matsumoto T, Kawamoto A, Kuroda R, Akimaru H, et al. A small interfering RNA targeting Lnk accelerates bone fracture healing with early neovascularization. Lab Investig 2013;93:1036–53. https://doi.org/10.1038/labinvest.2013.93.
  • [34] Wang T, Guo S, Zhang H. Synergistic Effects of Controlled-Released BMP-2 and VEGF from nHAC/PLGAs Scaffold on Osteogenesis. Biomed Res Int 2018;2018:3516463. https://doi.org/10.1155/2018/3516463.
  • [35] Li P, Bai Y, Yin G, Pu X, Huang Z, Liao X, et al. Synergistic and sequential effects of BMP-2, bFGF and VEGF on osteogenic differentiation of rat osteoblasts. J Bone Miner Metab 2014;32:627–35. https://doi.org/10.1007/s00774-013-0538-6.
  • [36] Bai Y, Li P, Yin G, Huang Z, Liao X, Chen X, et al. BMP-2, VEGF and bFGF synergistically promote the osteogenic differentiation of rat bone marrow-derived mesenchymal stem cells. Biotechnol Lett 2013;35:301–8. https://doi.org/10.1007/s10529-012-1084-3.
There are 36 citations in total.

Details

Primary Language English
Subjects Health Care Administration
Journal Section Original Research Articles
Authors

Berrin İyilikci 0000-0003-3602-8999

Ufuk Taşdemir 0000-0002-0631-1665

Özlem Özmen 0000-0002-1835-1082

Alper Kızıldağ 0000-0002-1630-3140

Project Number Project Number: 2018DİŞF011
Publication Date September 15, 2021
Submission Date May 29, 2021
Published in Issue Year 2021Volume: 24 Issue: 3

Cite

EndNote İyilikci B, Taşdemir U, Özmen Ö, Kızıldağ A (September 1, 2021) EFFECT OF TIDEGLUSIB WITH BONE GRAFTING ON NEW BONE FORMATION. Cumhuriyet Dental Journal 24 3 224–231.
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