CC BY-NC-ND 4.0 · Eur J Dent 2021; 15(01): 008-012
DOI: 10.1055/s-0040-1714039
Original Article

Role of Hydroxyapatite and Ellagic Acid in the Osteogenesis

Agung Satria Wardhana
1   Department of Dental Material, Faculty of Dentistry, Universitas Lambung Mangkurat, Banjarmasin, Indonesia
,
2   Department of Dental Material, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia
,
3   Department of Oral Biology, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia
,
4   Department of Oral Medicine, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia
› Author Affiliations

Abstract

Objective Ellagic acid (EA), a phenolic antioxidant, has benefits in bone health and wound healing. The combination of EA and hydroxyapatite (HA) (EA-HA) is expected to increase osteogenesis. The aim of this study was to analyze osteogenesis after application of EA-HA according to the number of osteoblasts and osteoclasts in the bone and the expression of the receptor activator of nuclear factor kappa-β ligand (RANKL), osteoprotegerin (OPG), and osteocalcin (OCN) protein.

Materials and Methods Thirty Wistar rats were assessed with bone defects created in the left femur. The defects were filled with EA-HA and then sutured. Control groups were filled with polyethylene glycol (PEG) or HA. Each group was sacrificed either 7 or 14 days after treatment.

Results The defects filled with EA-HA exhibited the highest number of osteoblasts and the greatest expression of OPG and OCN at both day 7 and day 14 (p = 0.000). Conversely, treatment with EA-HA resulted in lower numbers of osteoclasts and reduced RANKL staining at both time points (p = 0.000).

Conclusions EA-HA can increase osteogenesis in bone defects by increasing the number of osteoblasts and the expression of OPG and OCN.



Publication History

Article published online:
20 July 2020

© 2020. European Journal of Dentistry. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).

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  • References

  • 1 Nainggolan LI, Gunasagaran L. Prevalence of alveolar bone defect pattern in periodontitis patients with diabetes mellitus using bitewing radiography. J Dentomaxillofacial Sci 2018; 3 (02) 88
  • 2 Susanto H, Nesse W, Kertia N. et al. Prevalence and severity of periodontitis in Indonesian patients with rheumatoid arthritis. J Periodontol 2013; 84 (08) 1067-1074
  • 3 Kuć J, Sierpińska T, Gołębiewska M. Alveolar ridge atrophy related to facial morphology in edentulous patients. Clin Interv Aging 2017; 12: 1481-1494
  • 4 Levengood SL, Zhang M. Chitosan-based scaffolds for bone tissue engineering. J Mater Chem B Mater Biol Med 2014; 2 (21) 3161-3184
  • 5 Kattimani VS, Kondaka S, Lingamaneni KP. Hydroxyapatite—past, present, and future in bone regeneration. Bone Tissue Regen Insights 2016; 7: BTRI.S36138
  • 6 Polo-Corrales L, Latorre-Esteves M, Ramirez-Vick JE. Scaffold design for bone regeneration. J Nanosci Nanotechnol 2014; 14 (01) 15-56
  • 7 Hashemi ZS, Soleimani M. Tissue engineering scaffolds : history, types and construction methods tissue engineering scaffolds : history, types and construction methods. J Iran Anat Sci 2011; 9 (35) 146-168
  • 8 Medina S, Salazar L, Mejía C, Moreno F. In vitro behavior of the dentin and enamel calcium hydroxyapatite in human premolars subjected to high temperatures. Dyna (Bilbao) 2016; 83 (195) 34-41
  • 9 Dewi AH, Ana ID. The use of hydroxyapatite bone substitute grafting for alveolar ridge preservation, sinus augmentation, and periodontal bone defect: a systematic review. Heliyon 2018; 4 (10) e00884
  • 10 McKee MD, Pedraza CE, Kaartinen MT. Osteopontin and wound healing in bone. Cells Tissues Organs 2011; 194 (2-4) 313-319
  • 11 Primarizky H, Yuniarti WM, Lukiswanto BS. Ellagic acid activity in healing process of incision wound on male albino rats (Rattus norvegicus). KnE Life Sci 2018; 3 (06) 224
  • 12 Al-Obaidi MM, Al-Bayaty FH, Al Batran R, Hussaini J, Khor GH. Impact of ellagic acid in bone formation after tooth extraction: an experimental study on diabetic rats. Scientific World J 2014; 2014: 908098
  • 13 Surboyo MDC, Arundina I, Rahayu RP, Mansur D, Bramantoro T. Potential of distilled liquid smoke derived from coconut (Cocos nucifera L) shell for traumatic ulcer healing in diabetic rats. Eur J Dent 2019; 13 (02) 271-279
  • 14 Loi F, Córdova LA, Pajarinen J, Lin TH, Yao Z, Goodman SB. Inflammation, fracture and bone repair. Bone 2016; 86: 119-130
  • 15 Cohen N. Healing processes following tooth extraction in orthodontic cases. J Dentofac Anom Orthod 2014; 17: 304
  • 16 Shetty S, Kapoor N, Bondu J, Thomas N, Paul T. Bone turnover markers: Emerging tool in the management of osteoporosis. Indian J Endocrinol Metab 2016;20(6):846–52
  • 17 Parra-Torres AY, Valds-Flores M, Orozco L, Velzquez-Cruz R. Molecular Aspects of Bone Remodeling. In: Valds-Flores M. ed. Publicado en: Topics in Osteoporosis. InTech. 2013. London, UK: DOI: 10.5772/54905
  • 18 Mountziaris PM, Mikos AG. Modulation of the inflammatory response for enhanced bone tissue regeneration. Tissue Eng Part B Rev 2008; 14 (02) 179-186
  • 19 Agidigbi TS, Kim C. Reactive oxygen species in osteoclast differentiation and possible pharmaceutical targets of ROS-mediated osteoclast diseases. Int J Mol Sci 2019; 20 (14) 1-16
  • 20 Ahad A, Ganai AA, Mujeeb M, Siddiqui WA. Ellagic acid, an NF-κB inhibitor, ameliorates renal function in experimental diabetic nephropathy. Chem Biol Interact 2014; 219: 64-75
  • 21 Tobeiha M, Moghadasian MH, Amin N, Jafarnejad S. RANKL/RANK/OPG pathway: a mechanism involved in exercise-induced bone remodeling. BioMed Res Int 2020; 2020: 6910312
  • 22 Wright HL, McCarthy HS, Middleton J, Marshall MJ. RANK, RANKL and osteoprotegerin in bone biology and disease. Curr Rev Musculoskelet Med 2009; 2 (01) 56-64
  • 23 Yamaguchi M. RANK/RANKL/OPG during orthodontic tooth movement. Orthod Craniofac Res 2009; 12 (02) 113-119
  • 24 Belibasakis GN, Bostanci N. The RANKL-OPG system in clinical periodontology. J Clin Periodontol 2012; 39 (03) 239-248
  • 25 Al-Obaidi MM, Al-Bayaty FH, Al R Batran, Hassandarvish P, Rouhollahi E. Protective effect of ellagic acid on healing alveolar bone after tooth extraction in rat—a histological and immunohistochemical study. Arch Oral Biol 2014; 59 (09) 987-999
  • 26 Bickford PC, Tan J, Shytle RD, Sanberg CD, El-Badri N, Sanberg PR. Nutraceuticals synergistically promote proliferation of human stem cells. Stem Cells Dev 2006; 15 (01) 118-123
  • 27 Tanabe S, Santos J, La VD, Howell AB, Grenier D. A-type cranberry proanthocyanidins inhibit the RANKL-dependent differentiation and function of human osteoclasts. Molecules 2011; 16 (03) 2365-2374
  • 28 Maji K, Dasgupta S. Hydroxyapatite-chitosan and gelatin based scaffold for bone tissue engineering. Trans Indian Ceram Soc 2014; 73 (02) 110-114
  • 29 Li J, Wang G, Hou C, Li J, Luo Y, Li B. Punicalagin and ellagic acid from pomegranate peel induce apoptosis and inhibits proliferation in human HepG2 hepatoma cells through targeting mitochondria. Food Agric Immunol 2019; 30 (01) 898-913
  • 30 Weisburg JH, Schuck AG, Reiss SE. et al. Ellagic acid, a dietary polyphenol, selectively cytotoxic to HSC-2 oral carcinoma cells. Anticancer Res 2013; 33 (05) 1829-1836
  • 31 Hussein-al-ali SH, Al-qubaisi M, Rasedee A, Hussein MZ. Evaluation of the cytotoxic effect of ellagic acid nanocomposite in lung cancer A549 cell line and RAW 264. 9 cells. J Bionanoscience 2017; 11 (06) 578-583
  • 32 Patti A, Gennari L, Merlotti D, Dotta F, Nuti R. Endocrine actions of osteocalcin. Int J Endocrinol 2013; 2013: 846480
  • 33 Chapurlat RD, Confavreux CB. Novel biological markers of bone: from bone metabolism to bone physiology. Rheumatology (Oxford) 2016; 55 (10) 1714-1725
  • 34 Lovati AB, Lopa S, Recordati C. et al. In vivo bone formation within engineered hydroxyapatite scaffolds in a sheep model. Calcif Tissue Int 2016; 99 (02) 209-223
  • 35 Paldánius PM. The Role of Osteocalcin in Human Bone Metabolism and Glucose Homeostasis. Vol. 01. Helsinki: University of Helsinki; 2017: 1-95
  • 36 Domazetovic V, Marcucci G, Iantomasi T, Brandi ML, Vincenzini MT. Oxidative stress in bone remodeling: role of antioxidants. Clin Cases Miner Bone Metab 2017; 14 (02) 209-216