Genetic Impact on Bone Modulation—A Review Bridging Bioscience to Genetic Engineering

Abstract

Genes control approximately 60% to 75% of the variance of peak bone mass/density and a much smaller amount of variance in rate of loss.
Bone mass increases during growth to a peak value and soon after begins to decline. Most of the genetic effect is exerted during growth and so influences peak bone mass; whether there is an additional genetic effect on the rate of bone loss is less clear. So, this article aims to place emphasis on various oral and systemic conditions that are manifested due to altered gene function. Genetic polymorphisms and mutations are simple, although the consequences of the mechanism are complex. The syndromic manifestation due to changes at genetic level will greatly affect the bone quality, which will ultimately affect any treatment prognosis. Hence, a better understanding of molecular mechanisms of bone remodeling helps to identify pathogenic causes of bone, skeletal diseases, and leads to the development of targeted therapies for these diseases. This review highlights notions on the connecting link between science and genetics as well as various oral scenarios where gene could bring about changes, resulting in deformities. There is an intense research awaited in the future which could intervene with the causes that bring about genetic modulations, so as to decrease the mortality rate of humans.

Keywords

genetic / mutations / syndromes / bone / resorption

References

[1] Wellik DM, Capecchi MR.Hox10 and Hox11 genes are required to globally pattern the mammalian skeleton. Science 2003;301(5631):363-367

[2] Adler CP. Bones and bone tissue; normal anatomy and histology. In Bone Diseases New York: Springer-Verlag; 2000:1-30

[3] Zaidi M. Skeletal remodeling in health and disease. Nat Med 2007; 13(07):791-801

[4] Claflin RS.Healing of disturbed and undisturbed extraction wounds. J Am Dent Assoc 1936;23:945-959

[5] Atwood DA.Reduction of residual ridges: a major oral disease entity. J Prosthet Dent 1971;26(03):266-279

[6] Resorption level of edentulous alveolar bone in normal, osteopenia and osteoporosis postmenopausal women. J Prosthet Dent 2012;8(03):141-146

[7] Frutos R, Rodríguez S, Miralles-Jorda L, Machuca G. Oral manifestations and dental treatment in menopause. Med Oral 2002;7(01):26-30, 31-35

[8] Lerner UH.Inflammation-induced bone remodeling in periodontal disease and the influence of post-menopausal osteoporosis. J Dent Res 2006;85(07):596-607

[9] Cecconi BT, Asgar K, Dootz E.Clasp assembly modifications and their effect on abutment tooth movement. J Prosthet Dent 1972; 27(02):160-167

[10] Wactawski-Wende J.Periodontal diseases and osteoporosis: association and mechanisms. Ann Periodontol 2001;6(01):197-208

[11] Martínez-Maestre MA, González-Cejudo C, Machuca G, Torrejón R, Castelo-Branco C.Periodontitis and osteoporosis: a systematic review. Climacteric 2010;13(06):523-529

[12] Kornman KS, di Giovine FS. Genetic variations in cytokine expression: a risk factor for severity of adult periodontitis. Ann Periodontol 1998;3(01):327-338

[13] Nishimura I, Garrett N.Impact of Human Genome Project on treatment of frail and edentulous patients. Gerodontology 2004; 21(01):3-9

[14] Song J-H, Lee J-H.Single nucleotide polymorphisms and haplotypes in vascular endothelial growth factor gene and residual ridge resorption of mandible in Korean population. J Biomaterials Nanobiotechnology 2014;5:39-43

[15] AlSheikh HA, AlZain S, Shaik JP, Bhogoju S,Warsy A, Reddy Parine N. Two novel SNPs in genes involved in immune response and their association with mandibular residual ridge resorption. Saudi J Biol Sci 2020;27(03):846-852

[16] Jahangiri L, Devlin H, Ting K, Nishimura I.Current perspectives in residual ridge remodeling and its clinical implications: a review. J Prosthet Dent 1998;80(02):224-237

[17] Paek J, Oh Y, Kim J, Lee JH.Single nucleotide polymorphisms in HIF-1α gene and residual ridge resorption (RRR) of mandible in Korean population. Gene Expr 2015;16(03):137-144

[18] Kim JH, Oh MY, Paek J, Lee J.Association between FGFR1OP2/ wit3.0 polymorphisms and residual ridge resorption of mandible in Korean population. PLoS One 2012;7(08):e42734

[19] Kim JJ, Shon HC, Chang JH, et al.HIF-1 Alpha and VEGF expression in fracture healing. J Korean Orthop Assoc 2008;43:479-487

[20] Zhao T, Lv J, Zhao J, Nzekebaloudou M.Hypoxia-inducible factor- 1alpha gene polymorphisms and cancer risk: ameta-analysis. J Exp Clin Cancer Res 2009;28:159-169

[21] Atwood DA.Postextraction changes in the adult mandible as illustrated by microradiographs of midsagittal sections and serial cephalometric roentgenograms. J Prosthet Dent 1963;13: 810-824

[22] Nedelman C, Gamer S, Bernick S.The alveolar ridge mucosa in denture and non-denture wearers. J Prosthet Dent 1970;23(03): 265-273

[23] Suwanwela J, Lee J, Lin A, et al.A genetic association study of single nucleotide polymorphisms in FGFR1OP2/wit3.0 and long-term atrophy of edentulous mandible. PLoS One 2011;6(01):e16204

[24] Gunsolley JC, Califano JV, Koertge TE, Burmeister JA, Cooper LC, Schenkein HA.Longitudinal assessment of early onset periodontitis. J Periodontol 1995;66(05):321-328

[25] Baer PN.The case for periodontosis as a clinical entity. J Periodontol 1971;42(08):516-520

[26] Boughman JA, Halloran SL, Roulston D, et al.An autosomaldominant form of juvenile periodontitis: its localization to chromosome 4 and linkage to dentinogenesis imperfecta and Gc. J Craniofac Genet Dev Biol 1986;6(04):341-350

[27] Yucel-Lindberg T, Båge T.Inflammatory mediators in the pathogenesis of periodontitis. Expert Rev Mol Med 2013;15:e7

[28] Stefan A. Hienz, Sweta Paliwal, Saso Ivanovski. Mechanisms of Bone Resorption in Periodontitis. Hindawi Publ Cor J Immunol Research 2015;10;. Doi: 10.1155/2015/615486

[29] Liu D, Xu JK, Figliomeni L, et al.Expression of RANKL and OPG mRNA in periodontal disease: possible involvement in bone destruction. Int J Mol Med 2003;11(01):17-21

[30] Udagawa N, Takahashi N, Jimi E, et al.Osteoblasts/stromal cells stimulate osteoclast activation through expression of osteoclast differentiation factor/RANKL but not macrophage colony-stimulating factor: receptor activator of NF-kappa B ligand. Bone 1999; 25(05):517-523

[31] Styrkarsdottir U, Halldorsson BV, Gretarsdottir S, et al.Multiple genetic loci for bone mineral density and fractures. N Engl J Med 2008;358(22):2355-2365

[32] Styrkarsdottir U, Halldorsson BV, Gretarsdottir S, et al.New sequence variants associated with bone mineral density. Nat Genet 2009;41(01):15-17

[33] Gong Y, Vikkula M, Boon L, et al.Osteoporosis-pseudoglioma syndrome, a disorder affecting skeletal strength and vision, is assigned to chromosome region 11q12-13.AmJHumGenet 1996; 59(01):146-151

[34] Balemans W, Van Wesenbeeck L, Van Hul W.A clinical and molecular overview of the human osteopetroses. Calcif Tissue Int 2005;77(05):263-274

[35] Riches PL, McRorie E, Fraser WD, Determann C, van’t Hof R, Ralston SH. Osteoporosis associated with neutralizing autoantibodies against osteoprotegerin. N Engl J Med 2009;361(15):1459-1465

[36] Choi JY, Shin A, Park SK, et al.Genetic polymorphisms of OPG, RANK, and ESR1 and bone mineral density in Korean postmenopausal women. Calcif Tissue Int 2005;77(03):152-159

[37] Garnero P, Borel O, Grant SF, Ralston SH, Delmas PD.Collagen Ialpha1 Sp1 polymorphism, bone mass, and bone turnover in healthy French premenopausal women: the OFELY study. J Bone Miner Res 1998;13(05):813-817

[38] Langdahl BL, Ralston SH, Grant SF, Eriksen EF.An Sp1 binding site polymorphism in the COLIA1 gene predicts osteoporotic fractures in bothmen andwomen. J BoneMiner Res 1998;13(09):1384-1389

[39] Berg JP, Lehmann EH, Stakkestad JA, Haug E, Halse J.The Sp1 binding site polymorphism in the collagen type I alpha 1 (COLIA1) gene is not associated with bone mineral density in healthy children, adolescents, and young adults. Eur J Endocrinol 2000; 143(02):261-265

[40] Heegaard A, Jorgensen HL, Vestergaard AW, Hassager C, Ralston SH.Lack of influence of collagen type Ialpha1 Sp1 binding site polymorphism on the rate of bone loss in a cohort of postmenopausal danish women followed for 18 years. Calcif Tissue Int 2000;66(06):409-413

[41] Efstathiadou Z, Tsatsoulis A, Ioannidis JP.Association of collagen Ialpha 1 Sp1 polymorphism with the risk of prevalent fractures: a meta-analysis. J Bone Miner Res 2001;16(09):1586-1592

[42] Mann V, Ralston SH.Meta-analysis of COL1A1 Sp1 polymorphism in relation to bone mineral density and osteoporotic fracture. Bone 2003;32(06):711-717

[43] Lohmueller KE, Pearce CL, Pike M, Lander ES, Hirschhorn JN.Metaanalysis of genetic association studies supports a contribution of common variants to susceptibility to common disease. Nat Genet 2003;33(02):177-182

[44] Langdahl BL, Knudsen JY, Jensen HK, Gregersen N, Eriksen EF.A sequence variation: 713-8delC in the transforming growth factorbeta 1 gene has higher prevalence in osteoporotic women than in normal women and is associated with very low bone mass in osteoporotic women and increased bone turnover in both osteoporotic and normal women. Bone 1997;20(03):289-294

[45] Singla A, Sheikh S, Jindal SK, Brar R.The Papillon Lefevre syndrome: a bridge between a dermatologist and a dentist. J Clin Exp Dent 2010;2(01):e43-e46

[46] Sreeramulu B, Haragopal S, Shalini K, Sudha MD, Kiran G.The prosthodontic management of a young edentulous patient with the papillon lefevre syndrome-a rare case report. J Clin Diagn Res 2012;6(10):1808-1811

[47] Barnes AM, Chang W, Morello R, et al.Deficiency of cartilageassociated protein in recessive lethal osteogenesis imperfecta. N Engl J Med 2006;355(26):2757-2764

[48] Cabral WA, Chang W, Barnes AM, et al.Prolyl 3-hydroxylase 1 deficiency causes a recessive metabolic bone disorder resembling lethal/severe osteogenesis imperfecta. Nat Genet 2007;39(03): 359-365

[49] Gopinath VK, Manoj KM, Mahesh K.Hypohidrotic ectodermal dysplasia-a case report. J Indian Soc Pedod Prev Dent 1999;17(03):90-92

[50] Wright JT, Grange DK, Fete M. Hypohidrotic ectodermal dysplasia. In: Adam MP, Ardinger HH, Pagon RA, et al., eds. GeneReviews® [Internet]. Seattle (WA): University ofWashington, Seattle; 2017: 1993-2021. Available at: https://www.ncbi.nlm.nih.gov/books/NBK1112/

[51] Gorlin RJ, Pindborg JJ, Cohen MM.Syndromes of Head and Neck. 20th ed. New York: Mc Graw Hill; 1976:379-385

[52] Açil Y, Mobasseri AE, Warnke PH, Terheyden H, Wiltfang J, Springer I.Detection ofmature collagen in human dental enamel. Calcif Tissue Int 2005;76(02):121-126

[53] Barbosa MDFS, Nguyen QA, Tchernev VT, et al.Identification of the homologous beige and Chediak-Higashi syndrome genes. Nature 1996;382(6588):262-265

[54] Hajishengallis E, Hajishengallis G.Neutrophil homeostasis and periodontal health in children and adults. J Dent Res 2014;93(03): 231-237

RIGHTS & PERMISSIONS

2021 Global Medical Genetics