Draft:Human teeth

From Wikiversity
Jump to navigation Jump to search
Dentalmirror.jpg
Click to return to School of Dentistry
This is a frontal view of the teeth of a human adult male. Credit: David Shankbone.

Teeth of humans are small, calcified, hard, whitish structures found in the mouth. They function in mastication mechanically breaking down items of food by cutting and crushing them in preparation for swallowing and digestion. The roots of teeth are embedded in the maxilla (upper jaw) or the mandible (lower jaw) and are covered by gingiva gums. Teeth are made of multiple tissues of varying density and hardness.

Theory of teeth[edit]

The image is a model of a human molar-like tooth. Credit: Jmarchn.

Def. a "hard, calcareous structure present in the mouth of many vertebrate animals, generally used for eating"[1] is called a tooth.

The image on the right is a model of a human molar-like tooth. Its components are labeled:

  1. Tooth:
  2. Enamel
  3. Dentin
  4. Dental pulp:
  5. cameral pulp
  6. root pulp
  7. Cementum
  8. Crown
  9. Cusp
  10. Sulcus
  11. Cementoenamel junction or Neck
  12. Root
  13. Furcation
  14. Root apex
  15. Apical foramen
  16. Gingival sulcus
  17. Periodontium:
  18. Gingiva:
  19. free or interdental
  20. marginal
  21. alveolar
  22. Periodontal ligament
  23. Alveolar bone
  24. Vessels and nerves:
  25. dental
  26. periodontal
  27. alveolar through alveolar canals.

Genetics[edit]

Main source: Genetics
This is an image of Bob, the guinea pig. Credit: selbst.

Genetics involves the identification, expression, transmission, and variation of inherited characteristics.

Def. a "branch of biology that deals with the transmission and variation of inherited characteristics, in particular chromosomes and DNA"[2] is called genetics.

Sources[edit]

Main sources: Genetics/Sources and Sources

"Enamel cells ultimately determine the properties of dental enamel."[3]

Objects[edit]

Main sources: Genetics/Objects and Objects

Def. the "hard covering on the exposed part of a tooth"[4] is called the enamel.

Def. the "hard, dense calcareous material that makes up the bulk of a tooth"[5] is called the dentin.

Def. the "soft center of a tooth"[6] is called the pulp.

Liquid objects[edit]

This diagram names the genes that are part of the TNF signaling pathway for Homo sapiens (humans). Credit: Kanehisa Laboratories.

"Pulp cells from human permanent molars were isolated and established in culture; 40% showed positive alkaline phosphatase staining."[7]

The "cells formed a mineralized extracellular matrix; they could thus have the potential to differentiate into odontoblast-like cells in vitro."[7]

The "cells produced predominantly (~99%) type I collagen and only trace amount of type III collagen. The ratio of α1(I) to α2(I) procollagen chains was about 68:32, indicating that no significant amount of collagen type I trimer was synthesized in this system. The ratios of α1(I), α2(I) and α1(III) procollagen mRNAs were about 61:25:1; these were compatible with the ratios of corresponding procollagen a chains. In addition, a novel 5.8 kb proα1(III) mRNA was detected. These observations indicate that collagen synthesis in these cultured pulp cells was regulated at the transcriptional level."[7]

GeneID: 765 carbonic anhydrase 6 [ Homo sapiens (human) ].

"We also found that the haplotype (ACA) (rs2274328, rs17032907 and rs11576766) of the carbonic anhydrase VI was associated with a low number of decayed, missing, and filled teeth index with an odds ratio (95% confidence interval) of 0.635 (0.440-0.918)."[8]

"The rs17032907 genetic variant and the haplotype (ACA) of CA VI may be associated with dental caries susceptibility."[8]

GeneID: 3480 IGF1R insulin like growth factor 1 receptor [ Homo sapiens (human) ].

"IGF-1 regulates the metabolism of hard dental tissue through binding to the IGF-1 receptor on target cells. Furthermore, IGF-binding-protein-3 promotes the accessibility of IGF-1."[9]

"The teeth [showing ongoing development] showed significantly stronger expression of IGF-1 and IGF-1R. The major sources of all of the proteins investigated immunohistochemically in sections of wisdom teeth were odontoblasts, cementoblasts and cell colonies in the pulpal mesenchyme. [...] members of the IGF-1 family are involved in the late stage of tooth development and the process of pulpal differentiation."[9]

GeneID: 7124 TNF tumor necrosis factor [ Homo sapiens (human) ].

"Tumor necrosis factor-α (TNF-α) is involved in various inflammatory processes, including periodontitis. Although the influences of TNF-α on periodontal ligament fibroblasts and osteoblasts have been widely documented, its effects on cementoblasts, the cells responsible for cementum production, remain largely unknown."[10]

"TNF-α suppressed the mineralization ability of cementoblasts by inhibiting differentiation and inducing apoptosis."[10]

"Various signaling pathways [image on the right], such as p53, PP2AC, p38, Erk1/2, JNK, PI3K-Akt, and NF-κB, were activated during this process. The use of a specific inhibitor and siRNA transfection confirmed that the effects of TNF-α on differentiation and apoptosis in cementoblasts were partially abrogated by inhibiting p53 activity. By contrast, the effects of TNF-α were even exacerbated by the inhibition of the p38, Erk1/2, JNK, PI3K-Akt, and NF-κB pathways. Moreover, p53 activity was further enhanced by blocking the p38, Erk1/2, JNK, and PI3K-Akt signaling pathways."[10]

The "differentiation inhibition and apoptosis in cementoblasts induced by TNF-α were partially dependent on p53 activity. The p38, Erk1/2, JNK, PI3K-Akt, and NF-κB pathways were also activated but acted as balancing players to limit rather than conduct the negative effects of TNF-α. These balancing effects were dependent, or at least partially dependent, on p53, except for the NF-κB pathway."[10]

Rocky objects[edit]

GeneID: 860 RUNX2 runt-related transcription factor 2 [ Homo sapiens (human) ].

"This gene is a member of the RUNX family of transcription factors and encodes a nuclear protein with an Runt DNA-binding domain. This protein is essential for osteoblastic differentiation and skeletal morphogenesis and acts as a scaffold for nucleic acids and regulatory factors involved in skeletal gene expression. The protein can bind DNA both as a monomer or, with more affinity, as a subunit of a heterodimeric complex. Mutations in this gene have been associated with the bone development disorder cleidocranial dysplasia (CCD). Transcript variants that encode different protein isoforms result from the use of alternate promoters as well as alternate splicing."[11]

"Cleidocranial dysplasia (CCD) is characterized by the runt-related transcription factor 2 (RUNX2) mutation, which results in delayed tooth eruption due to disturbed functions of dental follicle. Accumulating evidence has revealed a key regulatory circuit, including RUNX2, miR-31, and special AT-rich binding protein 2 (SATB2) acting in concert in mesenchymal stem cell homeostasis and functions. However, whether such a regulatory loop works in dental follicle cells (DFCs) remains unknown."[12]

A "novel mutation on exon 5 (c.634T>G, p.T212P) in RUNX2 via exome sequencing in the [cleidocranial dysplasia] CCD patient [has] typical clinical presentations."[12]

"Compared with [dental follicle cells] DFCs from healthy donors, DFCs-CCD displayed significantly lower osteogenic, osteoclast-inductive, and matrix-degrading capacities and had lower RUNX2 (a transcriptional inhibitor of miR-31), higher miR-31, and downregulated [special AT-rich binding protein 2] SATB2. Lower ratios of RANKL/OPG and RANKL/RANK, as well as decreased expression of matrix metalloproteinase 9 (MMP9) and matrix metalloproteinase 2 (MMP2), would lead to inactivation of osteoclasts and suppression of bone matrix remodeling in DFCs-CCD. Furthermore, the roles of the RUNX2-miR-31-SATB2 loop in DFCs-CCD were revealed by endogenous miR-31 knockdown, which resulted in increased SATB2 and RUNX2, as well as osteoclast-inductive and matrix degradation capacities. Conversely, SATB2, RUNX2, MMP9, MMP2, and osteoclast-inductive factors expression declined upon ectopic miR-31 overexpression in normal DFCs. Importantly, neonatal mice with in vivo siRUNX2 delivery exhibited less activated osteoclasts around dental follicles and delayed tooth eruption."[12]

GeneID: 1277 COL1A1 collagen, type I, alpha 1 [ Homo sapiens (human) ].

"This gene encodes the pro-alpha1 chains of type I collagen whose triple helix comprises two alpha1 chains and one alpha2 chain. Type I is a fibril-forming collagen found in most connective tissues and is abundant in bone, cornea, dermis and tendon. Mutations in this gene are associated with osteogenesis imperfecta types I-IV, Ehlers-Danlos syndrome type VIIA, Ehlers-Danlos syndrome Classical type, Caffey Disease and idiopathic osteoporosis. [...] Two transcripts, resulting from the use of alternate polyadenylation signals, have been identified for this gene."[13]

Matrix metalloproteinases[edit]

"Matrix metalloproteinases (MMPs) are a group of proteolytic enzymes capable of degrading most components of the extracellular matrix."[14]

"MMPs may play a role in tissue degradation in inflamed dental pulp."[14]

Gene ID: 4313 MMP2 matrix metallopeptidase 2 [ Homo sapiens (human) ].

"The main gelatinase secreted by human pulp and [periodontal ligament] PDL cells migrated at 72 kDa and represented MMP-2."[14]

Gene ID: 4318 MMP9 matrix metallopeptidase 9 [ Homo sapiens (human) ].

"Minor gelatinolytic bands were also observed at 92 kDa regions that correspond to MMP-9."[14]

Alkaline phosphatases[edit]

GeneID: 249 ALPL alkaline phosphatase, liver/bone/kidney [ Homo sapiens (human) ].

ALPL is an alkaline phosphatase, liver/bone/kidney in humans. "The product of this gene is a membrane bound glycosylated enzyme that is not expressed in any particular tissue and is, therefore, referred to as the tissue-nonspecific form of the enzyme. The exact physiological function of the alkaline phosphatases is not known. A proposed function of this form of the enzyme is matrix mineralization; however, mice that lack a functional form of this enzyme show normal skeletal development. This enzyme has been linked directly to hypophosphatasia, a disorder that is characterized by hypercalcemia and includes skeletal defects. The character of this disorder can vary, however, depending on the specific mutation since this determines age of onset and severity of symptoms."[15] Bold added.

"Mutations in hypophosphatasia reduce the function of tissue nonspecific alkaline phosphatase, and the resulting increase in pyrophosphate contributes to bone and tooth mineralization defects by inhibiting physiologic calcium-phosphate precipitation."[15]

"Cementum is critical for anchoring the insertion of periodontal ligament fibers to the tooth root. Several aspects of cementogenesis remain unclear, including differences between acellular cementum and cellular cementum, and between cementum and bone. Biomineralization is regulated by the ratio of inorganic phosphate (Pi) to mineral inhibitor pyrophosphate (PPi), where local Pi and PPi concentrations are controlled by phosphatases including tissue-nonspecific alkaline phosphatase (TNAP) and ectonucleotide pyrophosphatase/phosphodiesterase 1 (NPP1)."[16]

"TNAP was associated with earliest cementoblasts near forming acellular and cellular cementum. With loss of TNAP in the Alpl null mouse, acellular cementum was inhibited, while cellular cementum production increased, albeit as hypomineralized cementoid. In contrast, NPP1 was detected in cementoblasts after acellular cementum formation, and at low levels around cellular cementum. Loss of NPP1 in the Enpp1 null mouse increased acellular cementum, with little effect on cellular cementum. Developmental patterns were recapitulated in a mouse model for acellular cementum regeneration, with early TNAP expression and later NPP1 expression. In vitro, cementoblasts expressed Alpl gene/protein early, whereas Enpp1 gene/protein expression was significantly induced only under mineralization conditions. These patterns were confirmed in human teeth, including widespread TNAP, and NPP1 restricted to cementoblasts lining acellular cementum. These studies suggest that early TNAP expression creates a low PPi environment promoting acellular cementum initiation, while later NPP1 expression increases PPi, restricting acellular cementum apposition. Alterations in PPi have little effect on cellular cementum formation, though matrix mineralization is affected."[16]

Transcription factors[edit]

GeneID: 860 RUNX2 runt-related transcription factor 2 [ Homo sapiens (human) ].

RUNX2 "is a member of the RUNX family of transcription factors and encodes a nuclear protein with an Runt DNA-binding domain. This protein is essential for osteoblastic differentiation and skeletal morphogenesis and acts as a scaffold for nucleic acids and regulatory factors involved in skeletal gene expression. The protein can bind DNA both as a monomer or, with more affinity, as a subunit of a heterodimeric complex. Mutations in this gene have been associated with the bone development disorder cleidocranial dysplasia (CCD)."[17]

RUNX2 is involved in "odontogenesis of [any] dentin-containing tooth [and] regulation of odontogenesis of [any] dentin-containing tooth".[17]

Homeoboxes[edit]

GeneID: 4487 MSX1 msh homeobox 1 [ Homo sapiens (human) ].

MSX1 "encodes a member of the muscle segment homeobox gene family. The encoded protein functions as a transcriptional repressor during embryogenesis through interactions with components of the core transcription complex and other homeoproteins. It may also have roles in limb-pattern formation, craniofacial development, particularly odontogenesis, and tumor growth inhibition. Mutations in this gene, which was once known as homeobox 7, have been associated with nonsyndromic cleft lip with or without cleft palate 5, Witkop syndrome, Wolf-Hirschom syndrome, and autosomoal dominant hypodontia."[18]

"Novel nonsense mutation in MSX1 causes tooth agenesis with cleft lip in a Chinese family. ... [T]he nonsense mutation in MSX1 might have resulted in rapid degradation of the mutated transcript and caused the phenotype of tooth agenesis with cleft lip in the Chinese family."[19]

"PAX9 and MSX1 gene mutation can cause different phenotypes of tooth agenesis."[19]

MSX1 is involved in "odontogenesis of [any] dentin-containing tooth".[19]

Gene ID: 5083 PAX9 paired box 9 [ Homo sapiens (human) ].

"This gene is a member of the paired box (PAX) family of transcription factors."[20]

"Mice lacking this gene exhibit impaired development of organs, musculature and the skeleton, including absent and abnormally developed teeth, and neonatal lethality. Mutations in the human gene are associated with selective tooth agenesis-3."[20]

"PAX9 and MSX1 gene mutation can cause different phenotypes of tooth agenesis."[19]

Tachykinin peptide hormones[edit]

GeneID: 6863 TAC1 tachykinin precursor 1 [ Homo sapiens (human) ].

TAC1 tachykinin, precursor 1 "encodes four products of the tachykinin peptide hormone family, substance P and neurokinin A, as well as the related peptides, neuropeptide K and neuropeptide gamma. These hormones are thought to function as neurotransmitters which interact with nerve receptors and smooth muscle cells. They are known to induce behavioral responses and function as vasodilators and secretagogues. Multiple transcript variants encoding different isoforms have been found for this gene."[21]

"Transcript variant beta encodes the full-length form of this gene. It encodes hormones substance P, neurokinin A, as well as the neuropeptide K."[22]

"As compared to the full-length transcript variant beta, variant alpha lacks exon 6, and therefore does not encode neuropeptide K, neurokinin A, or neuropeptide gamma. This transcript does encode the hormone substance P located on exon 3."[22]

"As compared to the full-length transcript variant beta, variant gamma lacks exon 4, and therefore does not encode neuropeptide K. This transcript does encode substance P, neurokinin A, and is the only variant that encodes neuropeptide gamma."[22]

"As compared to the full-length transcript variant beta, variant delta lacks both exons 4 and 6; therefore, it does not encode neurokinin A, neuropeptide K, or neuropeptide gamma. It does encode the hormone substance P located on exon 3."[22]

Notation: let CGRP stand for Calcitonin Gene-Related Peptide.

Notation: let NKA represent neurokinin A.

"Substance P and CGRP [are] present in [painful and healthy pulp tissue from human adult teeth] and NKA [is] detected in 96% of the pulps. CGRP [is] present in much higher concentrations than SP and NKA in both painful and non-painful teeth. The painful teeth had significantly higher concentrations of SP ..., NKA ... and CGRP ... than non-painful teeth. The concentration of CGRP [are] significantly higher in the pulps of smokers compared with non-smokers ...."[23]

Gene transcriptions[edit]

Main source: Gene transcriptions

GeneID: 8091 HMGA2 high mobility group AT-hook 2 [ Homo sapiens (human) ].

A genome-wide "association study identifies four loci [of GeneID: 8091 HMGA2 high mobility group AT-hook 2] associated with eruption of permanent teeth."[24]

Hypotheses[edit]

Main source: Hypotheses
  1. When the genome within each tooth is properly signaled, it will begin to heal the tooth from the inside out against caries and any other illness of the teeth.

See also[edit]

References[edit]

  1. tooth. San Francisco, California: Wikimedia Foundation, Inc. June 11, 2014. Retrieved 2014-07-01.
  2. genetics. San Francisco, California: Wikimedia Foundation, Inc. April 16, 2014. Retrieved 2014-05-07.
  3. Michael J. Hubbard (1998). "Enamel Cell Biology Towards a Comprehensive Biochemical Understanding". Connective Tissue Research 38 (1-4): 17-32. http://informahealthcare.com/doi/abs/10.3109/03008209809017013. Retrieved 2014-07-01. 
  4. enamel. San Francisco, California: Wikimedia Foundation, Inc. May 24, 2014. Retrieved 2014-07-01.
  5. dentin. San Francisco, California: Wikimedia Foundation, Inc. June 12, 2014. Retrieved 2014-07-01.
  6. pulp. San Francisco, California: Wikimedia Foundation, Inc. April 17, 2014. Retrieved 2014-07-01.
  7. 7.0 7.1 7.2 M.Y.P. Kuo, W.H. Lan, S.K. Lin, K.S. Tsai, L.J. Hahn (November 1992). "Collagen gene expression in human dental pulp cell cultures". Archives of Oral Biology 37 (11): 945-52. doi:10.1016/0003-9969(92)90066-H. http://www.sciencedirect.com/science/article/pii/000399699290066H. Retrieved 2014-07-01. 
  8. 8.0 8.1 ZQ Li, XP Hu, JY Zhou, XD Xie, JM Zhang (1 June 2015). "Genetic polymorphisms in the carbonic anhydrase VI gene and dental caries susceptibility". Genetics and Molecular Research 14 (2): 5986-93. doi:10.4238/2015.June.1.16. PMID 26125798. https://www.ncbi.nlm.nih.gov/pubmed/26125798. Retrieved 2016-11-27. 
  9. 9.0 9.1 G Magnucki, U Schenk, S Ahrens, A Navarrete Santos, CR Gernhardt, HG Schaller, C Hoang-Vu (2013). "Expression of the IGF-1, IGFBP-3 and IGF-1 receptors in dental pulp stem cells and impacted third molars". Journal of Oral Science 55 (4): 319-27. PMID 24351920. http://www.ncbi.nlm.nih.gov/pubmed/24351920. Retrieved 2015-12-10. 
  10. 10.0 10.1 10.2 10.3 YL Wang, H He, ZJ Liu, ZG Cao, XY Wang, K Yang, Y Fang, M Han, C Zhang, FY Huo (September 2015). "Effects of TNF-α on Cementoblast Differentiation, Mineralization, and Apoptosis". Journal of Dental Research 94 (9): 1225-32. PMID 26088424. http://www.ncbi.nlm.nih.gov/pubmed/26088424/. Retrieved 2015-12-10. 
  11. NCBI (6 December 2015). RUNX2 runt-related transcription factor 2 [ Homo sapiens (human) ]. Bethesda, Maryland USA: NCBI. Retrieved 2015-12-10.
  12. 12.0 12.1 12.2 J Ge, S Guo, Y Fu, P Zhou, P Zhang, Y Du, M Li, J Cheng, H Jiang (July 2015). "Dental Follicle Cells Participate in Tooth Eruption via the RUNX2-MiR-31-SATB2 Loop". Journal of Dental Research 94 (7): 936-44. PMID 25818585. http://www.ncbi.nlm.nih.gov/pubmed/25818585/. Retrieved 2015-12-10. 
  13. COL1A1 (6 December 2015). COL1A1 collagen, type I, alpha 1 [ Homo sapiens (human) ]. Bethesda, Maryland USA: NCBI. Retrieved 2015-12-10.
  14. 14.0 14.1 14.2 14.3 Yu-Chao Chang, Chung-Chih Lai, Shun-Fa Yang, You Chan, Yih-Shou Hsieh (February 2002). "Stimulation of Matrix Metalloproteinases by Black-Pigmented Bacteroides in Human Pulp and Periodontal Ligament Cell Cultures". Journal of Endodontics 28 (2): 90-3. http://www.sciencedirect.com/science/article/pii/S0099239905605894. Retrieved 2014-07-01. 
  15. 15.0 15.1 NCBI (June 16, 2013). ALPL alkaline phosphatase, liver/bone/kidney [ Homo sapiens (human) ]. 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 2013-06-21.
  16. 16.0 16.1 LE Zweifler, MK Patel, FH Nociti Jr, HF Wimer, JL Millán, MJ Somerman, BL Foster (23 March 2015). "Counter-regulatory phosphatases TNAP and NPP1 temporally regulate tooth root cementogenesis". International Journal of Oral Science 7 (1): 27-41. PMID 25504209. http://www.ncbi.nlm.nih.gov/pubmed/25504209. Retrieved 2015-12-10. 
  17. 17.0 17.1 NCBI (June 13, 2013). RUNX2 runt-related transcription factor 2 [ Homo sapiens (human) ]. 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 2013-06-21.
  18. RefSeq (July 2008). MSX1 msh homeobox 1 [ Homo sapiens (human) ]. 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 2013-06-21.
  19. 19.0 19.1 19.2 19.3 NCBI (June 11, 2013). MSX1 msh homeobox 1 [ Homo sapiens (human) ]. 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 2013-06-21.
  20. 20.0 20.1 PAX9 (6 December 2015). PAX9 paired box 9 [ Homo sapiens (human) ]. Bethsda, Maryland USA: NCBI. Retrieved 2015-12-10.
  21. RefSeq (July 2008). TAC1 tachykinin, precursor 1 [ Homo sapiens (human) ]. 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 2013-06-21.
  22. 22.0 22.1 22.2 22.3 NCBI (June 9, 2013). TAC1 tachykinin, precursor 1 [ Homo sapiens (human) ]. 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 2013-06-21.
  23. L. Awawdeh, F. T. Lundy, C. Shaw, P-J. Lamey, G. J. Linden, J. G. Kennedy (January 2002). "Quantitative analysis of substance P, neurokinin A and calcitonin gene-related peptide in pulp tissue from painful and healthy human teeth". International Endodontic Journal 35 (1): 30-6. doi:10.1046/j.1365-2591.2002.00451.x. http://onlinelibrary.wiley.com/doi/10.1046/j.1365-2591.2002.00451.x/abstract. Retrieved 2013-06-21. 
  24. HMGA2 (6 December 2015). HMGA2 high mobility group AT-hook 2 [ Homo sapiens (human) ]. NHGRI GWAS Catalog. Retrieved 2015-12-10.

External links[edit]

{{Chemistry resources}}{{Gene project}}{{Humanities resources}}{{Medicine resources}}