• Jessy Wijaya Clinical Dental Science Study Program, Faculty of Dentistry, Universitas Gadjah Mada, Yogyakarta, Indonesia
  • Rezmelia Sari Clinical Dental Science Study Program, Faculty of Dentistry, Universitas Gadjah Mada, Yogyakarta, Indonesia
  • Suryono Clinical Dental Science Study Program, Faculty of Dentistry, Universitas Gadjah Mada, Yogyakarta, Indonesia



Bone regeneration, Osteoblast differentiation, Propolis


Introduction: Optimal bone regeneration is contingent upon the activities of osteoblasts, which are modulated by signalling molecules. Propolis, an abundantly beneficial natural substance, has the potential to induce the release of signalling molecules.

Review: Four essential elements required for tissue regeneration via tissue engineering: scaffolds, signalling molecules, stem cells, and vascularization. Subsequently, osteoblast differentiation and activity are enhanced by signalling molecules induced by propolis. Propolis contains active ingredients that influence every stage of osteoblast differentiation. Propolis-induced increases in the release of signalling molecules (BMP, FGF, TGF) and the transcription factor RUNX2 stimulate the expression of diverse osteoblastogenic markers at each stage of differentiation: type I alpha 1 collagen during proliferation, alkaline phosphatase during maturation, and osteocalcin during mineralization.

Conclusion: Propolis has the capacity to promote bone regeneration through its involvement in all phases of osteoblast differentiation (inducing the release of signalling molecules, increasing the transcription factor, and increasing the expression of osteoblastogenic markers). Additional research is required to determine how propolis influences the equilibrium between osteoblast and osteoclast activities in order to maintain optimal bone homeostasis and remodelling. The prolonged duration of bone regeneration necessitates the use of a carrier for propolis to remain on bone defects for an extended period of time.


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Sanz M, Herrera D, Kebschull M, Chapple I, Jepsen S, Beglundh T, et al. Treatment of stage I–III periodontitis—The EFP S3 level clinical practice guideline. J Clin Periodontol 2020;47(S22):4–60. Doi:

Chen MX, Zhong YJ, Dong QQ, Wong HM, Wen YF. Global, regional, and national burden of severe periodontitis, 1990–2019: An analysis of the Global Burden of Disease Study 2019. J Clin Periodontol 2021;48(9):1165–88. Doi:

Suratri MAL, Jovina TA, Lelly A, Edwin VA, Ayu GAK. Pengaruh Hipertensi Terhadap Kejadian Penyakit Jaringan Periodontal (Periodontitis) pada Masyarakat Indonesia (Data Riskesdas 2018). Buletin Penelitian Kesehatan 2020;48(4):227–34. Doi:

Könönen E, Gursoy M, Gursoy UK. Periodontitis: A multifaceted disease of tooth-supporting tissues. J Clin Med 2019;8(8):1135. Doi:

Huang X, Xie M, Xie Y, Mei F, Lu X, Li X, et al. The roles of osteocytes in alveolar bone destruction in periodontitis. J Transl Med. BioMed Central Ltd 2020;18(479):1-15. Doi:

Tsuchida S, Nakayama T. Recent Clinical Treatment and Basic Research on the Alveolar Bone. Biomedicines 2023;11(3):843. Doi:

Lee HS, Byun SH, Cho SW, Yang BE. Past, present, and future of regeneration therapy in oral and periodontal tissue: A review. Appl Sci (Switzerland) 2019;9(6):1046. Doi:

Hutchings G, Moncrieff L, Dompe C, Janowicz K, Sibiak R, Bryja A, et al. Bone regeneration, reconstruction and use of osteogenic cells; from basic knowledge, animal models to clinical trials. J Clin Med 2020;9(1):139. Doi:

Amarasekara DS, Kim S, Rho J. Regulation of osteoblast differentiation by cytokine networks. Int J Mol Sci 2021;22(6): 2851. Doi:

López-Valverde N, Pardal-Peláez B, López-Valverde A, Flores-Fraile J, Herrero-Hernández S, Macedo-De-Sousa B, et al. Effectiveness of Propolis in the Treatment of Periodontal Disease: Updated Systematic Review with Meta-Analysis. Antioxidants 2021;10(2):269. Doi:

Elkhenany H, El-Badri N, Dhar M. Green propolis extract promotes in vitro proliferation, differentiation, and migration of bone marrow stromal cells. Biomed Pharmacother 2019; 115:108861. Doi:

Szwed-Georgiou A, Płociński P, Kupikowska-Stobba B, Urbaniak MM, Rusek-Wala P, Szustakiewicz K, et al. Bioactive Materials for Bone Regeneration: Biomolecules and Delivery Systems. ACS Biomater Sci Eng. American Chemical Society 2023;9(9):5222-54. Doi:

Cho YD, Kim KH, Lee YM, Ku Y, Seol YJ. Periodontal wound healing and tissue regeneration: A narrative review. Pharmaceuticals 2021;14(5):456. Doi:

Hajishengallis G, Chavakis T, Lambris JD. Current understanding of periodontal disease pathogenesis and targets for host-modulation therapy. Periodontol 2000;84(1):14-34. Doi:

Kwon TH, Lamster IB, Levin L. Current Concepts in the Management of Periodontitis. Int Dent J 2021;71(6):462–76. Doi:

Florencio-Silva R, Sasso GRDS, Sasso-Cerri E, Simões MJ, Cerri PS. Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells. Biomed Res Int. Hindawi Publishing Corporation 2015;2015(421746):1-17. Doi:

Kim JM, Lin C, Stavre Z, Greenblatt MB, Shim JH. Osteoblast-Osteoclast Communication and Bone Homeostasis. Cells. NLM (Medline) 2020;9(9):2073. Doi:

Ramanauskaite E, MacHiulskiene V. Antiseptics as adjuncts to scaling and root planing in the treatment of periodontitis: A systematic literature review. BMC Oral Health 2020;20(1). Doi:

Gaharwar AK, Singh I, Khademhosseini A. Engineered biomaterials for in situ tissue regeneration. Nat Rev Mats. Nature Research 2020;2020(5):686–705. Doi:

Goldman JA, Poss KD. Gene regulatory programmes of tissue regeneration. Nat Rev Gen. Nature Research; 2020;21(9):511–25. Doi:

Duda GN, Geissler S, Checa S, Tsitsilonis S, Petersen A, Schmidt-Bleek K. The decisive early phase of bone regeneration. Nat Rev Rheumatol. Nature Research 2023;19(2):78–95. Doi:

Ward E. A Review of Tissue Engineering for Periodontal Tissue Regeneration. J Vet Dent 2022;39(1):49–62. Doi:

Zullkiflee N, Taha H, Usman A. Propolis: Its Role and Efficacy in Human Health and Diseases. Molecules 2022;39(1). Doi:

Barboza A da S, Ribeiro de Andrade JS, Ferreira ML, Peña CLD, da Costa JS, Fajardo AR, et al. Propolis Controlled Delivery Systems for Oral Therapeutics in Dental Medicine: A Systematic Review. Vol. 11, Dentistry Journal 2023;11(7):162. Doi:

Kumar M, Prakash S, Radha, Lorenzo JM, Chandran D, Dhumal S, et al. Apitherapy and Periodontal Disease: Insights into In Vitro, In Vivo, and Clinical Studies. Antioxidants 2022;11(5):823. Doi:

Przybyłek I, Karpiński TM. Antibacterial properties of propolis. Molecules 2019;24(11):2047. Doi:

Somsanith N, Kim YK, Jang YS, Lee YH, Yi HK, Jang JH, et al. Enhancing of osseointegration with propolis-loaded TiO2 nanotubes in rat mandible for dental implants. Materials 2018;11(1):61. Doi:

Braakhuis A. Evidence on the health benefits of supplemental propolis. Nutrients 2019;11(11):2705. Doi:

Meimandi-Parizi A, Oryan A, Sayahi E, Bigham-Sadegh A. Propolis extract a new reinforcement material in improving bone healing: An in vivo study. Int J Surg 2018;56:94–101. Doi:

Zulhendri F, Lesmana R, Tandean S, Christoper A, Chandrasekaran K, Irsyam I, et al. Recent Update on the Anti-Inflammatory Activities of Propolis. Molecules 2022;27(23):8743. Doi:

Lara Pereira YC, Mardegan Issa JP, Watanabe E, Nascimento GC, Iyomasa MM, Del Ciampo JO, et al. The Therapeutic Use of Propolis Extract in Alveolar Bone Contaminated with Bacterial Endotoxin. Dentistry 2018;8(3):1-9. Doi: 10.4172/2161-1122.1000473

Lunardhi LC, Kresnoadi U, Agustono B. The effect of a combination of propolis extract and bovine bone graft on the quantity of fibroblasts, osteoblasts and osteoclasts in tooth extraction sockets. Dent J 2019;52(3):126–32. Doi:

Lim YK, Yoo SY, Jang YY, Lee BC, Lee DS, Kook JK. Anti-inflammatory and in vitro bone formation effects of Garcinia mangostana L. and propolis extracts. Food Sci Biotechnol 2020;29(4):539–48. Doi:

Baloch MM, Seriwatanachai D, Chanchoa C, Thanasrisuebwong P, Suebbuk S, Surarit R. Effect of Tetragonula laeviceps propolis from Thailand on periodontal ligament fibroblast. Pharm Sci Asia 2021;48(5):450–60. Doi:

Tang M, Wang G, Li J, Wang Y, Peng C, Chang X, et al. Flavonoid extract from propolis alleviates periodontitis by boosting periodontium regeneration and inflammation resolution via regulating TLR4/MyD88/NF-κB and RANK/NF-κB pathway. J Ethnopharmacol 2023;319(Pt3): 117324. Doi:

Rutkovskiy A, Stensløkken KO, Vaage IJ. Osteoblast Differentiation at a Glance. Med Sci Monit Basic Res 2016;22:95–106. Doi:

Ponzetti M, Rucci N. Osteoblast differentiation and signaling: Established concepts and emerging topics. Int J Mol Sci 2021;22(13):6651. Doi:

Khotib J, Gani MA, Budiatin AS, Lestari MLAD, Rahadiansyah E, Ardianto C. Signaling pathway and transcriptional regulation in osteoblasts during bone healing: Direct involvement of hydroxyapatite as a biomaterial. Pharmaceuticals 2021;14(7):615.


Kresnoadi U, Lunardhi LC, Agustono B. Propolis extract and bovine bone graft combination in the expression of VEGF and FGF2 on the preservation of post extraction socket. J Indian Prosthodont Soc 2020;20(4):417–23. Doi:

Suryono, Wijayanti P, Pramestri Lastianny S. The effect of carbonated hidroxyapatite-10% propolis application on open flap debridement towards transforming growth factor β1 expression. Mal J Med Health Sci 2023;19(SUPP4):45-51.

Kresnoadi U, Nizar M, Soekobagiono. Increased Expression of RUNX2 and ALP Resulting from a Combination of Propolis Extract and Bovine Bone Graft in Socket Preservation Material. Braz J Pharm Sci 2022;58:e20273. Doi:

Chen J, Lan Y, He Y, He C, Xu F, Zhang Y, et al. 99Tc-MDP-induced human osteoblast proliferation, differentiation and expression of osteoprotegerin. Mol Med Rep 2017;16(2):1801–9. Doi:

Lastianny SP, Sukmawati AN, Soesilowati ASK. Immunohistochemistry assay of osteocalcin on bone healing with CHA-10% propolis. J Dentomaxillofac Sci 2022;7(2):97–101. Doi: 10.15562/jdmfs.v7i2.1256.




How to Cite

Wijaya J, Sari R, Suryono. THE BENEFICIAL EFFECTS OF PROPOLIS ON OSTEOBLAST DIFFERENTIATION: A LITERATURE REVIEW. interdental [Internet]. 2024 Apr. 21 [cited 2024 Jun. 20];20(1):96-102. Available from: