bone morphogenetic protein in periodontics

bone morphogenetic protein involved in regeneration

1. BONE Morphogenetic PROTEINS BY- Dr. Srishty sharma 2 nd year PG student Dept of Periodontics

2. CONTENTS INTRODUCTION WHAT ARE BMP HISTORY CLASSIFICATION CHEMICAL STRUCTURE FUNCTIONS SIGNALLING MECHANISMS FACTORS AFFECTING BMP CARRIERS DELIVERY OF BMP PLEIOTROPISM OF BMP BMP IN PERIODONTAL REGENRATION CONCLUSIONS REFRENCES

3. INTRODUCTION Bone regeneration is comprised of a well-organized series of biological process - bone induction and conduction, involving- One of those signaling molecules is TGF-B superfamily Biggest subclass of TGF-B superfamily  BMP (most commonly used growth factor)

4. WHAT ARE BMP? Bone morphogenetic proteins (BMPs) are multifunctional growth factors  Shows biological activities  in various cell types, including

5. initiate, promote and maintain cartilage and   bone   morphogenesis , differentiation and regeneration in both the developing embryo and adult- MORPHOGENS

6. HISTORY

7. CLASSIFICATIONS Based upon amino acid sequences of the BMPs found in osteoinductive extracts of bone The human genome encodes 20 BMPs.

8. CHEMICAL STRUCTURE ( Sakou T 1998, Granjeiro JM et al. 2005, Huang YH et al. 2008 ) (McDonald and Hendrickson 1993)

9. Source : (Lynch SE et al. 1996, Lee MB 1997, Subach S 1997, Sakou T 1998) The available sources of BMPs are; 1) Human or animal bone matrices. 2) Recombinant DNA Technology. 3) Direct site application of DNA encoding for the desired factor

10. FUNCTIONS

11. Bmp6,7- type2 receptor Bmp2,4- type 1 receptor SIGNALLING MECHANISM Signal transduction cascade by binding to cell surface receptor forming heterotetrametric complex comprised of two dimers – type1/type2 serine kinase receptor Smad protein are directly activated and phosphorylated

12. Smad 4 enter the nucleus and acts on the gene sequence Transcription factors such as runx 2 and osterix to up-regulate their expression Endochondral and intramembranous bone formation

13. SIGNALLING PATHWAY

14. FACTOR AFFECTING BMP ACTIVITY

15. CARRIERS OF BMP An absorbable collagen sponge the first BMP carrier technology to be approved PRINCIPLE-

16. DIFFERENT CARRIERS

17. DELIVERY OF BMP

18. PLEIOTROPISM OF BMP Single gene affecting many phenotype BMP shows epithelial-mesenchymal interaction inductive mechanisms (i.e. the pleiotropic cascade of activities of BMP/OP gene products expression and cross-regulation of gene products of the osteogenic proteins of the transforming growth factor-b superfamily

19. BMP IN TOOTH MORPHOGENESIS BMP- 2,4,7 are expressed in dental epithelium Expressed in enamel knots BMP-2, 7- differentiation of odontoblast and ameloblast BMP- 3,7 immunolocalized for developing PDL,cementum and alveolar bone NAKASAMA 2003

20. BMP-3 – expressed in morphogenesis during developmental stages of mantle dentine deposition ( Lohara et al 2004) hence, cementogenesis and functionally oriented periodontal ligament fiber system BMP-2,3 – expressed in the morphogenesis periodontal tissues composite pattern of initiating bone formation by induction

21. BMP IN OSSEO-INDUCTION 3 PHASE OF BONE INDUCTION Initial 24 hours 3 days (Reddi et al 1987) After 5 days

22. HISTOLOGICAL IMAGE

23. (b) The alveolar bone surround the implant neck completely remodeled into a mature cortico-cancellous bone complex. 3D reconstructive image from CBCT (a)The demineralized buccal cortical bone

24. ELAINE ET AL 2015

25. BMP IN WOUND HEALING It appears that upon fracture BMP liberated from fracture gaps. And act as transcription factor- regulate proliferation and differentiation of mesenchymal cell ( Campbell and Kaplan 1992) Osteoblast observed at 7 days expressed BMP-2,3 involve in formation of bone and cartilage ( Lianjia and Yang 1990 ) Different BMP expressed in wound healing

26. Fresh fractures and non-unions treated with BMPs -reduces the rate of infection- increased stability by the increased osteoinduction activity and local vascular supply ( Termaat MF et al. 2005)

27. GENERAL USES OF BMPs IN DENTISTRY BMPs will enable new dental treatments for caries, endodontic, periodontal regeneration oral-maxillofacial surgery, alveolar ridge augmentation and cartilage repair in TMJ

28. Reparative dentin formed is double in BMP treated teeth (Lynch SE et al. 1996, Toyono T et al.1997, Granjeiro JM et al. 2005).

29. COMPONENTS OF BONE REGENERATION

30. BMP IN PERIODONTAL REGENRATION Rationale for using growth factor in periodontal regeneration is to enhance/accelerate physiologic wound healing capacity Application of rhBMP‑2 along with carrier system resulted  Substantial regeneration of bone and periodontal regeneration, provided that adequate space is maintained.

31. Alveolaor ridge augmentation rhBMP‑2  2 fold increase in alveolar ridge width, including a greater percentage of trabecular bone and a higher bone density compared to controls (P ≤ 0.05)(Miranda et al 2005) rhBMP‑2 dose ranging from 1.77 to 3.4 mg/patient generated an average of 8.51 mm of vertical bone height in 4 months( boyne 1997)

32. IMPLANT FIXATION Hanisch et al.  reported re‑ osseointegeration of endoosseous implants exposed to peri‑implantitis Jovanovic et al.  established normal physiologic bone formation, osseointegration, and long‑term functional loading of implants

33. Ripomonti et al 1994 studied efficacy of BMP in surgically created defect in male baboon and got histologic evidence of bone,cementum and periodontal ligament regenration SOME CLINICAL EVIDENCES

34. Effect of rhBMP was studied in surgically created supra-alveolar defect in beagle dogs  showing formation of cementum, however ankylosis occur because dose relation was not known ( wikeso 1999 ) Saito A et al 2009 studies have utilized rhBMP , determine their potential for correcting intrabony , supra‑alveolar, furcation, and fenestration defects

35. COMMERCIALLY AVAILABLE AS INFUSE bone graft kit (Supplied by MEDTRONIC) $4,499.0 COWELL BMP GRAFT (0.1G- 7,500) rhBMP2

36. OP-1 PUTTY (Supplied by Stryker Corp, Kalamazoo, Mich)

37. QUANTITY OF BMP high concentrations of BMPs are required (i.e. 100– 1000 ng/ml) at the local site to produce periodontal regeneration (Yamaguchi A) The partially purified recombinant BMPs consist of 0.5–115 µg to produce cartilage formation within 7 days and bone formation within 14 days.

38. CONCLUSIONS After decades of intense research BMPs have been shown in preclinical and clinical studies to enhance periodontal regeneration available data on use of rhBMP‑2 and 7 in humans are promising in showing an osteoinductive potential in periodontal regeneration, but not conclusive in the predictability and consistency results

39. Disconcerting issue however, is the cost of BMP which limits their clinical use, However, it’s hoped that the cost drops and BMP eventually become as affordable. Current active areas of research are centered on tissue engineering and gene therapy strategies that may result in more predictable regenerative outcomes in the future.

40. REFRENCES Kaur S, Grover V, Kaur H, Malhotra R. Evaluation of bone morphogenic proteins in periodontal practice. Indian J Dent. 2016 Jan-Mar;7(1):28-37. doi : 10.4103/0975-962X.179379. PMID: 27134452; PMCID: PMC4836095. Jain AP, Pundir S, Sharma A. Bone morphogenetic proteins: The anomalous molecules. J Indian Soc Periodontol . 2013 Sep;17(5):583-6. doi : 10.4103/0972-124X.119275. PMID: 24174749; PMCID: PMC3808010. Raza FB, Vijayaragavalu S, Vaidyanathan AK. Bone Morphogenetic Protein as Bone Additive around Dental Implant and its Impact on Osseointegration: a Systematic Review. J Dent (Shiraz). 2022 Sep;23(2 Suppl ):336-348. doi : 10.30476/DENTJODS.2021.90931.1536. PMID: 36588970; PMCID: PMC9789332. Sykaras N, Opperman LA. Bone morphogenetic proteins (BMPs): how do they function and what can they offer the clinician? J Oral Sci. 2003 Jun;45(2):57-73. doi : 10.2334/josnusd.45.57. PMID: 12930129.

41. Ugo Ripamonti ; Louise Renton (2006). Bone morphogenetic proteins and the induction of periodontal tissue regeneration. , 41(1), 73–87. doi:10.1111/j.1600-0757.2006.00155.x  Wozney , John M. (1995).  The Potential Role of Bone Morphogenetic Proteins in Periodontal Reconstruction*. Journal of Periodontology, 66(6), 506–510.  doi:10.1902/jop.1995.66.6.506  UME Wikesjö ; M Qahash ; Y-H Huang; A Xiropaidis ; G Polimeni ; C Susin (2009).  Bone morphogenetic proteins for periodontal and alveolar indications; biological observations – clinical implications. , 12(3), 263–270.  doi:10.1111/j.1601-6343.2009.01461.x Bal Z, Kushioka J, Kodama J, Kaito T, Yoshikawa H, Korkusuz P, Korkusuz F. BMP and TGF β use and release in bone regeneration. Turk J Med Sci. 2020 Nov 3;50(SI-2):1707-1722. doi : 10.3906/sag-2003-127. PMID: 32336073; PMCID: PMC7672355.

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