The induction of bone formation: From bone morphogenetic proteins to the transforming growth factor-β3 protein - Redundancy, pleiotropy and the induction of cementogenesis

Authors

DOI:

https://doi.org/10.17159/2519-0105/2021/v76no6a4

Keywords:

one morphogenetic proteins’ gene expression, qRTPCR, TGF-β3 master gene, noggin, molecular redundancy, pleiotropy, cementogenesis in angiogenesis, primates.

Abstract

This review proposes to translate organogenesis and the induction of bone formation by the recombinant human
transforming growth factor-β3 (hTGF-β3 ) in the Chacma baboon Papio ursinus to periodontal tissue induction and
regeneration. Naturally derived highly purified osteogenic proteins of the transforming growth factor-β (TGF-β) supergene family
were implanted in Class II furcation defects of the first and second mandibular molars. Additional defects in P.
ursinus were treated with recombinant human osteogenic protein-1 (hOP-1, also known as bone morphogenetic
protein-7, hBMP-7) and hBMP-2, singly or in binary applications. In different studies defects were also implanted with hTGF-β3
singly or in binary application with hOP-1. Harvested specimens on day 60 and 180 were processed for undecalcified histology using tungsten-carbide knives mounted on Polycut sledge’ micro-tomes or the Exakt precision cutting and grinding system.
Highly purified osteogenic proteins showed the induction of Sharpey’s fibres into newly formed cementoid with foci of mineralization. hOP-1 induced substantial cementogenesis whilst hBMP-2 preferentially induced alveolar bone. Intramuscular implantation of hTGF-β3 absorbed onto coral-derived macroporous bioreactors engineered large heterotopic multicellular bone organoids. Gene expression pathways by quantitative Reverse Transcription Polymerases Chain Reaction (qRT-PCR) show
that the induction of bone is via several profiled BMPs and TGF-βs expressed upon implantation of hTGF-β3 recapitulating the synergistic induction of bone as shown by binary applications of low doses of hTGF-β1 and hTGF-β3with hOP-1. The rapid induction of bone by hTGF-β3 provides theframework for a paradigmatic shift from recombinanthBMPs to hTGF-β3 in clinical contexts, provocatively operational in periodontal tissue regeneration with substantial induction of cementogenesis in angiogenesis.

Downloads

Download data is not yet available.

References

Ripamonti U. Developmental pathways of periodontal tissue regeneration. Developmental diversities of tooth morphogenesis do also map capacity for periodontal tissue regeneration? J Periodont Res. 2019; 54(1), 10-26. https://doi: 10.1111/jre. 12596. Epub 2018 Sep 12.

Ripamonti U, Heliotis M, van den Heeer B,Reddi AH. Bone morphognetic proteins induce periodontal regeneration in the baboon (Papio ursinus). J Periodont Res, 1994; 29(6), 439-45. https://doi: 10.1111/j.1600-0765.1994.tb01246.x.

Ripamonti U, Reddi AH. Periodontal regeneration: potential role of bone morphogenetic proteins. J Periodont Res, 29(4), 225-35. https://doi: 10.1111/j.1600-0765.1994.tb01216.x.

Ripamonti U. Induction of cementogenesis and periodontal ligament regeneration by bone morphogenetic proteins. In

Bone Morphogenetic Proteins: Biological Characteristics and Reconstructive Repair. TS Lindholm, (Ed.) RG Landes Company and Academic Press, Inc., 1996; (17). 189-98.

Ripamonti U, Heliotis M, Sampath TK, Rueger D. Induction of cementogenesis by recombinant human osteogenic protein-1 (hOP-1/BMP-7) in the baboon (Papio ursinus). Arch Oral Biol, 1996; 41(1), 121-6. https:/doi: 10.1016/0003-9969(95)001 10-7.

Ripamonti U, Reddi AH. Tissue engineering, morphogenesis and regeneration of periodontal tissues by bone morphogenetic proteins. Crit Rev Oral Biol Med, 1997; 8(2), 154-63. https://doi: 10.1177/10454411970080020401.

Thomadakis G, Ramoshebi, LN, Crooks J, Rueger DC, Ripamonti U. Immunolocalization of bone morphogenetic protein -2 and -3 and osteogenic protein-1 during murine tooth root morphogenesis and in other craniofacial structures. European. Journal of Oral Sciences, 1999; 107(5), 368-77. https:- //doi: 10.1046/j.09098836.1999.eos107508.x.

Ripamonti U, Crooks J, Petit J-C, Rueger DC. Periodontal tissue regeneration by combined applications of recombinant human osteogenic protein-1 and bone morphogenetic protein-2. A pilot study in Chacma baboons (Papio ursinus). European. Journal of Oral Sciences, 2001; 109(4), 241-8. https://doi:10.1034/j.16000722.2001.00041.x.

Ripamonti U. Recapitulating development: a template for periodontal tissue engineering. Tissue Engineering. 2007; 13(1),

-71. https://doi:10.1089/ten.2006.0167.

Teare JA, Ramoshebi LN, Ripamonti U. Periodontal tissue regeneration by recombinant human transforming growth factor

-β3 in Papio ursinus. Journal of Periodontal Research, 2008; 43(1), 1-8. https://doi:10.1111/j.1600-0765.2007.00987.x.

Ripamonti U, Ramoshebi LN, Teare J, Renton L, Ferretti C. The induction of endochondral bone formation by transforming growth factor-β3 : Experimental studies in the non-human primate Papio ursinus. J Cell Mol Med. 2008; 12(3), 1029-48. https://doi: 10.1111/j.1582-4934.2008.00126.x.

Ripamonti U, Teare J, Petit J-C. Induction of cementogenesis and periodontal ligament by bone morphogenetic proteins.

In S Vukicevic (Ed.), Bone Morphogenetic Proteins: From Local to Systemic Therapeutics. Birkauser Verlag AG, Basel/ Switzerland. 2008; 233-56.

Ripamonti U, Parak R, Petit J-C. Induction of cementogenesis and periodontal ligament regeneration by recombinant human transforming growth factor-ß3 in Matrigel with rectus abdominis responding cells. J Periodont Res. 2009; 44(1), 141-52. https://doi:10.1111/j.1600-0765.2008.01086.x.

Ripamonti U, Petit J-C, Teare J. Cementogenesis and the induction of periodontal tissue regeneration by the osteogenic proteins of the transforming growth factor-ß superfamily.J Periodont Res. 2009; 44(2): 81-7. https://doi.org/10.1111/j.1600-0765.2008.01158.x.

Ripamonti U, Petit J-C. Bone morphogenetic proteins, cementogenesis, myoblastic stem cells and the induction of periodontal tissue regeneration. Cyt Growth Factor Rev. 2009;20 (5-6), 489-99. https://doi.org/10.1016/jcytogfr.2009.10.016

Ripamonti U, Klar M, Renton LF, Ferretti C. Synergistic induction of bone formation by hOP-1, hTGF-β3 and inhibition by

zoledronate in macroporous coral derived hydroxyapatites. Biomaterials, 2010; 31(25): 6400-10. https://doi: 10.1016/j.biomaterials.2010.04.037. Epub 2010 May 21.

Ripamonti U, Petit J-C, Teare J. Tissue Engineering of the Periodontal Tissues In: Regenerative Dentistry, MK Marei and

KA Athanasiou (Eds) Morgan & Claypool Publishers. 2010; (3): 83-109.

Ripamonti U. Redefining the induction of periodontal tissue regeneration in primates by the osteogenic proteins of the

transforming growth factor-β supergene family. J Periodont Res, 2016; 51(6): 699-715. https://doi: 10.1111/jre.12356.

Epub Feb 2.

Ripamonti U, Parak R, Klar RM, Dickens C, Dix-Peek T, Duarte R. Cementogenesis and osteogenesis in periodontal

tissue regeneration by recombinant human transforming growth factor-β3: a pilot study in Papio ursinus. J Clin Periodontol,

; 44(1), 83-95. https://doi: 10.1111/jcpe.12642. Epub 2016 Dec 1.

Levander G. Tissue induction. Nature. 1945; 155: 148-9. https://doi.org/10.1038/155148a0.

Urist MR. Bone: formation by autoinduction. Science. 1965;150(3698): 893,899,220,680-6. http://doi: 10.1126/science.

3698.893.

Sampath TK, Reddi AH. Dissociative extraction and reconstitution of extracllular matrix components involved in local bone differentiation. Proc Natl Acad Sci USA, 1981; 78(12): 7599-603. https://doi.1073/pnas.78.12.7599.

Sampath TK, Reddi AH. Homology of bone inductive proteins from human, monkey, bovine, and rat extracellular matrix.

Proc Natl Acad Sci USA, 1983; 80(21): 6591-95. https://doi: 10.1073/pnas.80.21.6591

Reddi AH. Bone morphogenesis and modeling: soluble siganls sculpt osteosomes in the solid state. 1997; Cell, 89(2): 159-61. https://doi: 10.1016/s0092-8674(00)80193-2.

Urist MR, Silverman BF, Büring K, Dubuc FL, Rosenberg JM. The bone induction principle. Clin Orthop Rel Res, 1967; 53: 243-83.

Ripamonti U. Osteogenic proteins of the transforming growth factor-ß superfamily. In: HL Henry and AW Norman (Eds.),

Encyclopedia of Hormones. Academic Press, 2003; 80-6.

Ripamonti U. Soluble osteogenic molecular signals and the induction of bone formation. Biomaterials, 2006; 27(6): 807-22.

https://doi:10.1016/j.biomaterials.2005.09.021. Epub 2005 Oct 5.

Ripamonti U, Ferrett, C, Heliotis M. Soluble and insoluble signals and the induction of bone formation: Molecular therapeutics recapitulating development. J Anat, 2006; 209(4): 447-68. https://doi: 10.1111/j.1469-7580.2006.00635.x.

Kilkenny C, Browne WJ,Cuthill IC, Emerson M, Altman DG. Improving bioscience research reporting the ARRIVE guidelines for reporting animal research. PLoS Biol. 2010; 8, c1000412.

Turing AM. The chemical basis of morphogenesis. Phil Transact Royal Soc London. Series B, Biol Sci. 1952; B237(641): 37-72.

Ripamonti U. Functionalized surface geometries induce “Bone:Formation by autoinduction”. Front Physiol. 2018; 8: 1084

https://doi: 10.3389/fphys.2017.01084.

Sacerdotti C, Frattin G. Sulla produzione eteroplastica dell’ osso. Rivista Accademica Medica, Torino. 1901; 27: 825-36.

Huggins CB. The formation of bone under the influence of epithelium of the urinary tract. Arch Surg. 1931; 22: 377-408.

Trueta J. The role of vessels in osteogenesis. J Bone Joint Surg. 1963; 45B: 402-18.

von Haller A. Experimentorium de ossium formatione, In Opera minora, Vol. 2, Grasset F, Ed. Lausanne. 1973; 400.

Lanza D, Vegetti M. Opere biologiche di Aristotele. A cura di Diego Lanza e Mario Vegetti, UTET, Torino. 1971.

Crivellato E, Nico B, Ribatti D. Contribution of endothelial cells to organognesis: a modern reappraisal of an old Aristotelian

concept. J Anatomy. 2007; 211(4): 415-27. https://doi: 10.1111/j.1469-7580.2007.00790.x. Epub 2007 Aug 7.

Gomez-Salinero JM, Rafii S. Endothelial cell adaptation in regeneration. Science. 2018; 362(419): 1116-11. https://doi: 10.

/science.aar4800.

Senn N. On the healing of aseptic bone cavities by implantation of antiseptic decalcified bone. Am J Med Sci, 1889; 98: 219-43. https://doi: 10.1097/00000658-188907000-00043.

Reddi AH. Morphogenesis and tissue engineering of bone and cartilage: inductive signals, stem cells, and biomimetic biomaterials. Tissue Eng. 2000; 6(4): 351-59. https://doi: 10.1089/107632700418074.

Levander G. A study of bone regeneration. Surg Gynec Obst, 1938; 67(6): 705-14.

Levander G, Willestaedt H. Alcohol-soluble osteogenetic substance from bone marrow. Nature, 1946; 4,157: 87. https://doi: 10.1038/157587b0.

Moss ML. Extraction of an osteogenic inductor factor from bone. Science. 1958; 127(3301): 755-6. https://doi: 10.1126/science.127.3301.755.

Reddi AH, Huggins CB. Biochemical sequences in the transformation of normal fibroblast in adolescent rats. Proc Natl

Acad Sci USA, 1972; 69(6): 1601-5. https://doi: 10.1073/ pnas.69.6.1601.

Ripamonti U, Heliotis M, Ferretti C. Bone morphogenetic proteins and the induction of bone formation: From laboratory to patients. Oral Maxfac Surg.Clin of North Am, 2007; 19(4): 575-89. https://doi: 10.1016/j.coms.2007.07.006.

Vukicevic S, Luyten FP, Kleinman HK, Reddi AH. Differentiation of canalicular cell processes in bone cells by basement membrane matrix components: regulation by discrete domains oflaminin. Cell. 1990; 63(2) 437-45. https://doi: 10.1016/0092-

(90)90176-f.

Kusumbe AP, Ramasamy SK, Adams RH. Coupling of angiogenesis and osteogenesis by a specific vessel subtype in bone. Nature. 2014; 507: 323-8. https://doi: 10.1038/nature13145. Epub 2014 Mar 12.

Ramasamy SK, Kusumbe AP, Adams RH. Regulation of tissue morphogenesis by endothelial cell-derived signals. Trends in Cell Biol. 2015; 25(3): 148-57. https://doi: 10.1016/j.tcb.2014.11.007. Epub 2014 Dec 17.

Medici D, Shore EM, Lounev VY, Kaplan FS, Kalluri R. Conversion of vascular endothelail cells into multipotent stem-like

cells. Nature Med. 2010; 16(12): 1400-06. https://doi: 10.1038/nm.2252. Epub 2010 Nov 21.

Ramasamy SK, Kusumbe, AP, Wang L, Adams RH. Endothelial Notch activity promotes angiogenesis and osteogenesis in

bone. Nature. 2014; 507(7492): 376-80. https:// doi: 10.1038/nature13146. Epub 2014 Mar 12.

Heliotis M, Ripamonti U. Phenotypic modulation of endothelial cells by bone morphogenetic protein fractions in vitro. In Vitro

Cell Develop Biol, 1994; 30A(6): 353-5. https://doi: 10.1007/BF02634354.

Leversha M, Brennan C,Tabar V. Glioblastoma stem-like cells give rise to tumour endothelium. Nature. 2010; 468(7325),

-33. https://doi:10.1038/nature09624. Epub 2010 Nov 21.

Ripamonti U, Parak R, Klar MR, Dickens C, Dix-Peek T, Duarte R. The synergistic induction of bone formation by the

osteogenic proteins of the TGF-β supergene family. Biomaterials. 2016; 104: 279-96. https://doi: 10.1016/j.biomaterials.

07.018. Epub 2016 Jul 20.

Ripamonti U, Duneas N, van den Heever B, Bosch C, Crooks J.Recombinant transforming growth factor-β1

induces endochondral bone in the baboon and synergizes with recombinant osteogenic protein-1 (bone morphogenetic protein-7) to initiate rapid bone formation. J Bone Miner Res, 1997; 12(10): 1584-95. https://doi: 10.1359/jbmr.1997.12.10.1584.354 > RESEARCH

Klar RM, Duarte R, Dix-Peek T, Ripamonti U. The induction of bone formation by the recombinant human transforming

growth factor-β3. Biomaterials. 2014; 35(9), 2773-88. https://doi: 10.1016/j.biomaterials.2013.12.062. Epub 2014 Jan 15.

Ripamonti U. Osteogenic device for inducing bone formation in clinical contexts. US 2012/0277879 A1. 2012; Publication

date 1 November 2012.

Ripamonti, U. Osteogenic device for inducing bone formation in clinical contexts. US 9,084,757 B2. 2015; Publication date

July 2015.

Ripamonti, U. Induction of Bone Formation in Primates. The Transforming Growth Factor beta 3, CRC Press, Taylor & Francis Group, Boca Raton, USA, 2016.

Massagué J, Blain W, Lo RS. TGFbeta signaling in growth control, cancer, and heritable disorders. Cell. 2000; 103(2):

-309. https://doi: 10.1016/s0092-8674(00)00121-5.

Kicheva A, González-Gaitán M. The Decapentaplegic morphogen gradient: a precise definition. Curr Opin Cell Biol, 2008; 20(2), 137-43. https://doi: 10.1016/j.ceb.2008.01.008.

Ripamonti U, Dix-Peek T, Parak R, Milner B, Duarte R. Profiling bone morphogenetic proteins and transforming growth

factor-βs by hTGF-β3 pre-treated coral derived macroporous constructs: The power of one. Biomaterials, 2015; 49: 90-102. https://doi: 10.1016/j.biomaterials.2015.01.058. Epub 2015 Feb 14.

Ripamonti U, Duarte R, Ferretti C. Re-evaluating the induction of bone formation in primates. Biomaterials, 2014; 35: 9407-22.

https://doi:10.1016/j.biomaterials.2014.07.053. Epub 2014 Aug 23.

Ripamonti U, Duarte R, Parak R, Dickens C, Dix-Peek T, Klar RM. Redundancy and molecular evolution: The rapid induction of bone formation by the mammalian transforming growth factor-β3 isoform. Front Physiol, 2016; 7, 396. https://doi: 10.3389/fphys.2016.00396. eCollection 2016.

Shi Y, Massagué J. Mechanisms of TGF-beta signaling from cell membrane to the nucleus. Cell. 113(6): 685-700. https://

doi: 10.1016/s0092-8674(03)00432-x.

Feng XH, Derynck R. (2005). Specificity and versatility in tgfbeta signaling through. Smads. Annual Rev Cell Dev Biol,

; 21: 659-93. https://doi: 10.1146/annurev.cellbio.21.022404.142018.

Massagué J, Seoane J, Wotton D. Smad transcription factors. Genes Develop, 2005; 19(23): 2783-810. https://doi:

1101/gad.1350705.

Ross S, Hill CS. How the Smads regulate transcription. Int J Biochem Cell Biol. 2008; 40(3): 383-408. https://doi: 10.10

/j.biocel.2007.09.006. Epub 2007 Oct 7.

Mullen AC, Orlando A, Newman JJ, Lovén J, Kumar RM, Bilodeau S, Reddy J, Guenther MG, DeKoter RP, Young RA.

Master transcription factors determine cell-type-specific responses to TGF-β signaling. Cell. 2001; 147(3): 565-76. https://

doi: 10.1016/j.cell.2011.08.050.

Massagué J, Wotton D. Transcriptional control by the TGFbeta/Smad signaling system. EMBO J. 2000; 19(8): 1745-54.

https://doi: 10.1093/emboj/19.8.1745.

Lee KS, Hong SH, Bae S.C. Both the Smad and p38 MAPK pathways play a crucial role in Runx2 expression following

induction by transforming growth factor-beta and bone morphogenetic protein. Oncogene, 2002; 21(47): 7156-63. https://doi: 10.1038/sj.onc.1205937.

Derynck R, Zhang YE. Smad-dependent and mad-independent pathways in TGF-beta Family signaling. Nature, 2003; 425

(6958), 577-84. https://doi: 10.1038/nature02006.

Phinney DG, Prockop DJ. Concise review: mesenchymal stem/multipotent stromal cells: the state of transdifferentiation

and modes of tissue repair - current views. Stem Cells. 2007; 25(11): 2896-902. https://doi: 10.1634/stemcells.2007-

Epub 2007 Sep 27

Seo B-M, Miura M, Gronthos S, et al. Investigation of multipotent postnatal stem cells. From human periodontal ligament. Lancet, 2004; 364(9429): 149-55. https://doi: 10.1016/S0140-6736(04)16627-0.

Lin NH, Menicanin D, Mrozik K, Gronthos S, Bartold PM. Putative stem cells in regenerating human periodontium. J

Periodont Res, 2008; 43(5), 514-23. https://doi: 10.1111/j.1600-0765.2007.01061.x.

Jian H, Shen X, Liu I, Semenov M, He X, Wang X-F. Smad3-dependent nuclear translocation of β-catenin is required for

TGF-β1-induced proliferation of bone marrow derived adult human mesenchymal stem cells. Genes & Dev. 2006; 20:

-74.

Crisan M, Yap S, Casteilla L, et al. A perivascular origin for mesenchymal stem cells in multiple human organs. Cell Stem

Cell, 2008; 3(3), 301-13. https://doi: 10.1016/j.stem.2008.07. 003.

Wang X, Harris RE, Bayston LJ, Ashe HL. Type IV collagens regulate BMP signalling in Drosophila. Nature, 2008; 455

(7209): 72-77. https://doi: 10.1038/nature07214.

Sampath TK, Raska KE, Doctor JS, Tucker RF, Hoffmann FM.Drosophila transforming growth factor beta superfamily proteins induce endochondral bone formation in mammals. Proc Natl Acad Sci USA, 1993; 90(13): 6004-08. https://doi: 10.1073/pnas.90.13.6004.

Roberts AB, Sporn MB, Assoian RK, et al. Transforming growth factor type beta: Rapid induction of fibrosis and angiogenesis in vivo and stimulation of collagen formation in vitro. Proc Natl Acad Sci USA, 1986; 83(12): 4167-71. https://doi: 10.1073/pnas.83.12.4167.

Assoian RK, Komoriva A, Meyers CA, Miller DN, Sporn MB.Transforming growth factor-beta in human platelets. Identification of a major storage site, purificaton, and characterization. J Biol Chem. 1983; 258(11): 7155-60.

Robey, PG, Young MF, Flanders KC, Roche NS, Kondaiah P, Reddi AH, Termine JD, Sporn MB, Roberts AB. Osteoblasts synthetize and respond totransforming growth factor-type beta (TGF-beta) in vitro. J Cell Biol. 1987; 105(1): 457-63. https://doi: 10.1083/jcb.105.1.457.

Centrella M, Massagué J, Canalis E. Human platelet-derived transforming growth factor-β stimulates parameters of bone growth in fetal rat calvaria. Endocrinology, 1986; 119(5), 2306-12. https://doi: 10.1210/endo-119-5-2306.

Noda J, Camilliere JJ. In vivo stimulation of bone formation by transforming growth factor-β. Endocrinology, 1989; 124(6),

-4. https://doi: 10.1210/endo-124-6-2991.

Joyce ME, Roberts AB, Sporn MB, Bolander ME. Transforming growth factor-β and the initiation of chondrogenesis

and osteogenesis in the rat femur. J Cell Biol, 1990; 110(6): 2195-2207. https://doi: 10.1083/jcb.110.6.2195.

Seeherman HJ, Berasi SP, Brown CT, Martinez RX, Juo ZS, Jelinsky S, Cain MJ, Grode J, Tumelty KE, Bohner M, et al. A BMP/activin A chimera is superior to native BMPs and induces bone in nonhuman primates when delivered in a composite matrix. Science Translational Medicine. 2019; 11(489): eaar4953. https://doi: 10.1126/scitranslmed.aar4953.

Ripamonti U, Duarte R. Tissue Transfiguration in vivo. South African Provisional Patent Spec. 2019/08010, Dec. 3, 2019.

Ripamonti U, van den Heever B, Heliotis M, Dal Mas I, Hahnle U, Biscardi A. Local delivery of bone morphogenetic proteins using a reconstituted basement membrane gel: Tissue engineering with Matrigel. 2002; South Afr J Sci, 2002; 98 (9-10), 429-33.

Fatehullah A, Tan SH, Barker N. Organoids as an in vitro model of development and disease. Nature Cell Biol, 2016; 18(3):

-54. https://doi: 10.1038/ncb3312.

Balooch G, Balooch M, Nalla RK, Schilling S, Filvaroff EH, Marshall G., Marshall SJ, Ritchie RO, Derynk, R, Alliston T. TGF-β regulates the mechanical properties and composition of the bone matrix. Proc Natl Acad Sci USA. 2005; 102(52): 18813-18. https://doi: 10.1073/pnas.0507417102. Epub 2005Dec 14. < 355 www.sada.co.za / SADJ Vol. 76 No. 6

Ripamonti U, Crooks J, Matsaba T, Tasker T. Induction of endochondral bone formation by recombinant human transforming growth factor-β2 in the baboon (Papio ursinus).Growth Factors. 2000; 17(4): 269-85. https://doi: 10.3109/08977190009028971.

Ferretti C, Ripamonti U. Long-term follow-up of pediatric mandibular reconstruction with human transforming growth

factor-β3. J Craniofac Surg. 2020; 31(5), 1424-29. https://doi: 10.1097/SCS.0000000000006568.

Helder MN, Kar H, Bervoets TJM, Vukicevic S, Burger EH, D’Souza RN, Wöltgens JHM, Karsenty G, Bronkers ALJJ. Bone morphogenetic proteion-7 (Osteogenic Protein-1, OP-1) and tooth developent. J Dent Res, 1998; 77(4), 545-54. https://doi: 10.1177/ 002203459807 70040701.

Ripamonti U, Vukicevic S. Bone morphogenetic proteins: from developemntal biology to molecular therapeutics. South Afr J Sci. 1995; 91(6), 277-80.

Choi H, Ahn Y-H, Kim T-H, Bae C-H, Lee J-C, You H-K, Cho E-S (2016). TGF-β signaling regulates cementum formation through Osterix expression. Sci Rep. 2016; 6, 26046; https://doi: 10.1038/srep26046(2016).

Cao Z, Liu R, Zhang H, Liao H, Zhang Y, Hinton RJ, Feng JQ.Osterix controls cementoblasts differentiation through down regulation of Wnt-signaling via enhancing DKK1 expression. Int J Biol Sci. 2015; 11(3): 335-44. Doi:10.7150/ijbs.10874.

Tan SH, Senarath-Yapa K, Chung MT, Longaker MT, Wu JY, Nusee R. Wnts produced by osterix-expressing osteolineage

cells regulate their proliferation and differentiation. Proc Natl Acad Sci USA. 2014; E5262-E5271.

Wang C, Liao H, Sun H, Zhang Y, Cao Z. MicroRNA-3064-3p regulates the differentiation of cementobslasts through targeting DKK1. J Periodont Res. 2018; 53: 705-13.

Teare JA, Petit J-C, Ripamonti U. Synergistic induction of periodontal tissue regeneration by binary application of human osteogenic protein-1 and human transforming growth factor-β3in Class II furcation defects of Papio ursinus. J Periodont Res, 2012; 47(3): 336-44. https://doi: 10.1111/j.1600-0765.2011.01438.x.

Luan X, Walker C, Dangaria S, et al. The mosasaur tooth attachment apparatus as paradigm for the evolution of the gnathostome periodontium. Evol Develop. 2009; 11(3): 247-59 .https://doi 10.1111/j.1525-142X.2009.00327.x.

Downloads

Published

2021-07-31

How to Cite

Ripamont, U. (2021). The induction of bone formation: From bone morphogenetic proteins to the transforming growth factor-β3 protein - Redundancy, pleiotropy and the induction of cementogenesis. South African Dental Journal, 76(06), 331–356. https://doi.org/10.17159/2519-0105/2021/v76no6a4