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Table of Contents
Year : 2020  |  Volume : 7  |  Issue : 3  |  Page : 69-71

Role of growth factors in bone regeneration

1 Senior Resident, Guru Teg Bahadur Hospital, New Delhi, India
2 Senior Lecturer, Teerthanker Mahaveer Dental College and Research Centre, Moradabad, Uttar Pradesh, India
3 Head of Department, ARSMH Hospital; Senior Dentist; Prosthodontist, Smile Designing Center, Pune, Maharashtra, India
4 Senior Lecturer, MIDSR Dental College; Private Practitioner, Jadhav Dental Clinic, Latur, Maharashtra, India

Date of Submission24-Jun-2020
Date of Acceptance24-Jul-2020
Date of Web Publication29-Sep-2020

Correspondence Address:
Dr. Ankit Agarwal
Guru Teg Bahadur Hospital, New Delhi
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/INPC.INPC_26_20

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Regeneration of periodontal structures lost during periodontal diseases constitutes a complex biological process regulated among others by interactions between cells and growth factors. Growth factors are biologically active polypeptides affecting the proliferation, chemotaxis, and differentiation of cells from the epithelium, bone, and connective tissue.

Keywords: Enamel matrix proteins, fibroblast growth factor, insulin-like growth factor, platelet-derived growth factor, transforming growth factor

How to cite this article:
Agarwal A, Singh N, Khan M, Nabi Khan SS, Sahu K, Jadhav SU. Role of growth factors in bone regeneration. Int J Prev Clin Dent Res 2020;7:69-71

How to cite this URL:
Agarwal A, Singh N, Khan M, Nabi Khan SS, Sahu K, Jadhav SU. Role of growth factors in bone regeneration. Int J Prev Clin Dent Res [serial online] 2020 [cited 2020 Oct 24];7:69-71. Available from: https://www.ijpcdr.org/text.asp?2020/7/3/69/296537

  Introduction Top

According to the classic theory of root formation and attachment apparatus development, Hertwig epithelial root sheath (HERS) which is the apical extension of the enamel organ induces the mesenchymal cell of the dental papilla to form the mantle predentin before it disintegrates and leaves the root surface. As a result of HERS apoptosis during the embryonic process, the physical barrier it forms between the mesenchymal cells of the dental follicle and the forming dentin disintegrates. The mesenchymal cells that have been exposed to the newly formed dentin are induced to differentiate into cement oblasts and are responsible for cementogenesis. The process of cementum deposition is a prerequisite for the formation of both periodontal ligament (PDL) and the alveolar bone.[1] However, recombinations between slices of root dentin surface are not a sufficient stimulus for cement oblast differentiation and cementogenesis. Instead, it appears that there is an obligatory intermediate short and specific modulating stage in which the HERS cells secrete enamel-related matrix proteins.[2],[3],[4] The major fraction of enamel matrix proteins is composed of amelogenins, a family of hydrophobic proteins that account for more than 90% of the organic constituent of the enamel matrix. The second largest component of the enamel matrix proteins is the enamelins. It includes proline-rich enamelin, tuftelin, and tuft proteins. The enamel matrix is generally believed to regulate the initiation, propagation, termination, and maturation of the enamel hydroxyapatite crystallites.[5]

Enamel matrix derivative (EMD) is now commercially available for the treatment of periodontal defects as Emdogain® (Biora AB, Malmφ, Sweden) which has received the Food and Drug Administration approval. It is purified acidic extract of the developing embryonal enamel derived from 6-month old piglets. Its purpose is to act as a tissue healing modulator that would mimic the events that occur during the root development and to help to stimulate periodontal regeneration.[6],[7]

The Emdogain vehicle

The amelogenins which are the hydrophobic constituent of the enamel matrix proteins aggregate and become practically insoluble at a physiological pH and body temperature. They can be dissolved in an acidic or alkaline pH environment and low temperature. A suitable formulation should thus have a nonneutral pH and allow for gradual re-precipitation of the matrix when physiological conditions are re-established. The first marketed EMD product was supplied in a lyophilized form and was dissolved in an aqueous solution of propylene glycol alginate (PGA) immediately prior to use.[6] Since mixing EMD with PGA needs extra assistance and time, a new ready to use product Emdogain Gel was developed. It is a premixed formulation of EMD where the protein has been stabilized by heat treatment prior to being mixed with the vehicle. Both the formulation contain 30 mg EMD protein/ml PGA gel with a viscosity of about 2.5 pascal-second.

EMD may also promote periodontal regeneration by reducing dental plaque. In an ex vivo dental plaque model, it was found that EMD had an inhibitory effect on dental plaque viability. The effect of EMD on the growth of periodontal pathogens was further evaluated in vitro. Freshly prepared EMD or its vehicle (PGA) alone was added to calibrated suspension of microbes. A marked inhibitory effect of EMD on the growth of Gram-negative periodontal pathogens was demonstrated and the Gram-positive bacteria were unaffected. It was concluded that EMD has a positive effect on the composition of bacterial species in the postsurgical periodontal wound by selectively restricting the growth of periopathogens that can hamper wound healing and reduce the outcome of regenerative procedures. The results from thesein vitro studies indicate that EMD regulates multiple cell types in the healing site, while at the same time modulating the bacterial composition. EMD enhances proliferation rate, metabolism and protein synthesis, cellular attachment rate, and mineral nodule formation of PDL cells and has a similar influence on cementoblast and osteoblasts. In contrast to its effect on mesenchymal cells, EMD appears to inhibit the proliferation and the growth of epithelial cells.

Most of the effects of EMD are on mature cells rather than on multipotent precursors, suggesting that it may not be capable of controlling the entire regenerative process. At high concentration, EMD inhibits terminal differentiation of cementoblast with respect to mineralized module formation. This supports the idea that EMD is important for increasing the pool of cells required for periodontal regeneration and for stimulating the early differentiation process, but other factors in environment for certain cell types may be required to continue the regenerative process in vitro. Other proven abilities of EMD are inhibitory effects on dental plaque viability which can also contribute to regenerative results.[8],[9]

  Growth Factors in Periodontal Regeneration Top

Growth factors are polypeptide molecules released by the cells in the inflamed area that regulates events in the wound healing. These are naturally occurring proteins that regulate various aspects of cell growth and development acting locally or systemically. Growth factor is a general term to denote a class of polypeptide hormones that stimulate a variety of cellular events such as proliferation, chemotaxis differentiation, and production of extracellular matrix (ECM) proteins. Initially, growth factors were described as soluble molecules, but with present evidence, it is clear that binding of growth factors to the ECM is a major mechanism which regulates growth factor activity. Growth factors are proteins that may act locally or systemically to effect the growth and function of cells in several ways, exogenous growth factor can be used to supplement natural growth factors in wound healing which serves as the basis for upcoming regenerative therapies.[10]

Rationale of using growth factor in periodontal regeneration

When an injury occurs, a well-orchestrated cell–cell and cell-ECM interaction is initiated which begins the healing process. A complex activity of various molecules including cytokines and growth factors begins in the inflamed area, initiating the ECM remodeling. Tissue repair studies conducted on animals provide evidence that key growth factors involved in wound healing include epidermal growth factor, transforming growth factor-α and β, platelet-derived growth factor, and fibroblast growth factor.[11] Studies have shown that if any of these chemical mediators are removed from the healing site, the process of healing is hampered.[12]

  Bone Morphogenetic Protein Top

Bone morphogenetic proteins (BMPs) were discovered originally on the basis of their presence in osteoinductive extracts of bone matrix. Molecular cloning of BMPs demonstrated that they are a family of related differentiation factors, each capable of inducing the formation of new bone tissue when implanted. Two of the molecules in clinical use, recombinant human BMP-2 and recombinant human BMP-7 (OP-1), are produced in a biotechnology process using recombinant deoxyribonucleic acid technology that offers unlimited supply and substantial control over purity and reproducible activity. A third material, bovine BMP extract, is extracted from the bone and contains a mixture of BMP molecules. Each of these molecules, although osteoinductive in vivo, has different physiologic roles and biologic activitiesin vivo and in vitro.

BMP guides the modulation and differentiation of mesenchymal cells into bone and bone marrow cells. Absorbable collagen sponge (ACS) containing recombinant human BMP-2 has been approved for clinical use in certain oral surgery procedures, including localized alveolar ridge augmentation, under the name INFUSE® Bone Graft (Medtronic, Minneapolis, MN, USA) and InductOS™ (Wyeth, Maidenhead, UK). These ACS release the protein over time in the location where it is implanted and provides a scaffold on which new bone can grow. As the graft site heals, the ACS is absorbed and replaced by the bone.[13],[14],[15]

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Slavkin HC, Boyde A. Cementum: An epithelial secretory product? J Dent Res 1975;53:157.  Back to cited text no. 1
Slavkin HC. Towards a cellular and molecular understanding of periodontics. Cementogenesis revisited. J Periodontol 1976;47:249-55.  Back to cited text no. 2
Slavkin HC, Diekwisch TG. Molecular strategies of tooth enamel formation are highly conserved during vertebrate evolution. Ciba Found Symp 1997;205:73-80.  Back to cited text no. 3
Brookes SJ, Robinson C, Kirkham J, Bonass WA. Biochemistry and molecular biology of amelogenin proteins of developing dental enamel. Arch Oral Biol 1995;40:1-4.  Back to cited text no. 4
Hammarström L. Enamel matrix, cementum development and regeneration. J Clin Periodontol 1997;24:658-68.  Back to cited text no. 5
Heijl L, Heden G, Svärdström G, Ostgren A. Enamel matrix derivative (EMDOGAIN) in the treatment of intrabony periodontal defects. J Clin Periodontol 1997;24:705-14.  Back to cited text no. 6
Petinaki E, Nikolopoulos S, Castanas E. Low stimulation of peripheral lymphocytes, followingin vitro application of Emdogain. J Clin Periodontol 1998;25:715-20.  Back to cited text no. 7
Somani R, Zaidi I, Jaidka S. Platelet rich plasma-a healing aid and perfect enhancement factor: Review and case report. Int J Clin Pediatr Dent 2011;4:69-75.  Back to cited text no. 8
Antoniades HN, Scher CD, Stiles CD. Purification of human platelet-derived growth factor. Cell Biol 1979;76:1809-13.  Back to cited text no. 9
Morgan DO, Edman JC, Standring DN, Fried VA, Smith MC, Roth RA, et al. Insulin-like growth factor II receptor as a multifunctional binding protein. Comp Study 1987;329:301-7.  Back to cited text no. 10
Dionne CA, Jaye M, Schlessinger J. Structural diversity and binding of FGF receptors. Ann N Y Acad Sci 1991;638:161-6.  Back to cited text no. 11
Xu X, Weinstein M, Li C, Deng C. Fibroblast growth factor receptors (FGFRs) and their roles in limb development. Cell Tissue Res 1999;296:33-43.  Back to cited text no. 12
Linkhart TA, Mohan S, Baylink DJ. Growth factors for bone growth and repair: IGF, TGF beta and BMP. Bone 1996;19:1S-12S.  Back to cited text no. 13
Rosier RN, O'Keefe RJ, Hicks DG. The potential role of transforming growth factor beta in fracture healing. Clin Orthop Relat Res 1998;335:S294-300.  Back to cited text no. 14
Massagué J, Wotton D. Transcriptional control by the TGF-beta/Smad signaling system. EMBO J 2000;19:1745-54.  Back to cited text no. 15


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