Growth Hormone In Tooth Development Health And Social Care Essay

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1st Jan 1970 Health And Social Care Reference this

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Tooth development is the process where teeth are formed from the developing tooth bud, growing and maturing until it erupts into the mouth. This process is known as odontogenesis. There are several stages to odontogenesis which include the development of the tooth bud and the formation of hard tissue (Thesleff 2006). Within this paper, I will be discussing whether growth hormone has an effect on the development of the tooth bud and formation of hard tissue (in particular enamel and dentine formation).

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Growth hormone (GH) is produced by the pituitary gland, which is stimulated or inhibited by growth hormone releasing hormone (GHRH) and somatostatin respectively in the hypothalamus. GH stimulates the liver, for the production of insulin-like growth factor (IGF-1) (Laron et al citied by Laron Z. 2001); this has an effect on bones (particularly long bones) and muscles and other tissue growth. Gotz el al (2006) says that IGFs are ‘growth factors controlling pre- and post natal development and growth processes.’ Furthermore, IGF-1 and GH are able to induce bone morpogenic proteins (BMP) messenger RNA (mRNA), in particular BMP-2 and 4 mRNA(Li et al 1998). The study that was carried out showed that GH and IGF-1 increased the production of BMP-2 mRNA by up to 5-fold and BMP-4 mRNA by up to 4-fold.

In the developing tooth bud, there are four main stages; these include: the bud stage, the cap stage, the bell stage and crown stage.

Figure 1: A schematic drawing of the bud stage – the arrow shows the formation of the tooth bud (tb) within the dental lamina (dl) where dental mesenchyme (dm) has condensed around the tooth bud (Adapted from Joseph et al 1994)

dl

dm

The bud stage is the tooth bud appearance, however, there is no arrangement of the cells – figure 1 illustrates this stage showing that this stage is just a group of cells by the dental lamina. Li and colleagues (1998) carried out a study which showed that BMP-4 mRNA was present in the dental epithelium during this stage until the cap stage. This suggests that BMP-4 is needed for the cells so that they are able to combine and form the dental papilla from this unorganised arrangement. In addition to this, GH and its receptor was reported to be involved in allow process like ‘induction, epithelial-mesenchymal interactions, cellular proliferation’ (Zhang et al 1997). The study was able to show that GH was present at embryonic day 17/18 in the rat, which represents the bud stage of odontogenesis in the rat.

However, a study conducted by Zhang and colleagues (1992) brought up a very important point. This being that the pituitary gland is still forming when tooth bud formation occurs. Thus, if the gland is still forming, GH would not be able to play a role during the bud stage. Therefore, it is possible that a GH-like molecule might be involved during the bud stage; however, it has not been confirmed.

The cap stage is when ectomesenchymal cells combine and become the dental papilla. Additionally, the tooth bud begins to grow around the ectomesenchymal cells, combine producing a cap appearance and becomes the dental (or enamel) organ. Eventually the dental papilla will produce dentine (and pulp) and the enamel organ will produce enamel. It is shown that during the cap stage numerous cells of the dental epithelium and mesenchyme were intensely immunoreactive for GH (Zhang et al 1997). This suggests that GH is involved in the formation of the enamel organ and dental papilla, which are needed to form enamel and dentine respectively. Furthermore, studies (Joseph et al 1994) found out that GH receptors were Figure 2: A schematic drawing of the late cap stage showing the dental follicle (df) containing the dental/enamel organ and dental papilla (dp). The dental/enamel organ is starting to differentiate into the outer dental epithelium (ode) and inner dental epithelium (ide). (Adapted from Joseph et al 1994)

dp

expressed in the epithelium (where the enamel organ is located) and also in ectomesenchymal cells (where the dental papilla is located). Thus, showing that the receptors for GH are present indicating that GH is able to activate the receptors which are needed to activate the cells. This evidence both support the idea that GH is needed for the differentiation of ectomesenchymal cells to form the dental papilla and dental organ.

Figure Figure 3: A schematic drawing of the bell stage: Differentiation of the dental/enamel organ and dental papilla (dp) occurs. The enamel oragn differentiates into the outer dental epithelium (ode), inner dental epithelium (ide), stellate reticulum (sr) and stellate intermedium (si). The dental papilla differentiates into the outer and central mesenchymal cells of the dental/enamel organ.

The bell stage (named because the dental organ is shaped as a bell) is when histodifferentiation and morphodifferentiation of the dental papilla and enamel organ take place. Joseph and his colleagues (1994) showed that in the early period of the bell stage, there is growth of the dental organ, as cubical inner epithelium differentiates into columnar cells. Additionally, immunoreacitivity for GH receptor/binding protein found that the outer and inner enamel epithelium and stratum intermedium were positive, signifying that the growth hormone receptor is involved in the differentiation of the enamel organ. This in turn allows the inner enamel epithelium to differentiate into ameoblasts, outer enamel epithelium to provide a protective barrier during enamel production and finally, stratum intermedium is needed for enamel production to occur. However, the dental papilla and stellate reticulum were negative for immunoreactivity of GH receptor/binding protein. This suggests that dental papilla does not need GH to differentiate nor does the stellate reticulum which is needed as support for enamel production.

The tables below (table 1 and 2) summarises the immunoreactivity expression of growth hormone at various stages of tooth development, including the bud and cap stage. It is clearly shown that in the stages for developing tooth germ, GH, its receptor and binding protein are expressed in various cells throughout the stages.

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Table : Immunoreactivity expressed in the epithelium of a embryonic rat mandible showing the presence of GH, GH receptor and GH binding protein during embryonic day 17, 16, 20/21 and post natal day 9. The results are recorded show the intensity of the expression: +++ STRONG, ++ MODERATE, + MILD & +/- EQUIVOCAL (Zhang et al 1997)

Table 2: Immunoreactivity expressed in the mesenchyme of a embryonic rat mandible showing the presence of GH, GH receptor and GH binding protein during embryonic day 17, 16, 20/21 and post natal day 9. The results are recorded show the intensity of the expression: +++ STRONG, ++ MODERATE, + MILD & +/- EQUIVOCAL (Zhang et al 1997)The finally stage of the developing tooth bud is the crown (or maturation) stage. This is when the hard tissue (enamel and dentine) start to develop. Thus, the inner enamel epithelial cells start to change shape and differentiate into ameloblasts and the dental papilla changes in both size and shape and differentiate into odontoblasts to form dentine. This leads to the two processes commonly known as amelogenesis (formation of enamel) and dentinogenesis (formation of dentine).

Symons et al (2000) showed that there immunoreactivity of the IGF-1 receptor present during the maturation of the ameloblasts. Thus, it indicates that IGF-1 (via its receptor) is involved during amelogenesis. This shows that IGF-1 is needed for the ameloblasts to remove organic material and water (Nanci et al 1987), with increased flux of calcium and phosphate ions (Borke et al 1993)

Caviedes-Bucheli et al (2009) study was investigating real time PCR in mouse pulp cultures. The found out that IGF-1 can enhance the mineralisation of enamel (& dentine). The way it was able to do this was by inducing expressions of specific genes (Caton et al 2005)

In addition to is, Caton et al (2005) was investigating the effect that IGF-1 would have on tooth development in vitro. The results showed that the samples treated with IGF-1 had an increased enamel extracellular matrix, when compared to the control samples. This shows that there is increased enamel and dentine when IGF-1 was present, indicating that IGF-1 has a positive effect on the enamel and dentine formation.

The majority of the studies show the presence of GH and its receptor within cells. Smid and colleagues (2007) carried out an experiment when mouse molar teeth had a GH deficiency. The results shows that when there is a deficiency the crown dimensions were affected as the total crown area and the mesiodistal width at the cement-enamel junction (CEJ) was significantly smaller, when compared to when GH was present. This indicates that GH is needed to ensure growth of the tooth enamel and dentine, and when there is a deficiency, it affected the size of molar teeth.

Crown formation is finished when the inner enamel epithelium and outer enamel epithelium forms a double layers of HERS. This starts to proliferate apically and starts root morphogenesis. Yamashiro et al (2003) found out that BMP-2, -3, -4 and -7 were expressed during root formation and was associated with the differentiation of hard tissues. In particular, BMP-4 and -7 were expressed in ameloblasts – which indicate that they are needed for formation of enamel. Furthermore, expression of BMP-4 was also noted in cementoblasts which is needed for the production of primary acellular cementum and secondary cellular cementum (where acellular cementum is found on the cervical third and middle of the roots and attaches to principle fibres in the periodontal ligament and cellular cementum is located on the apical third of the root – Cho & Grant 2000 citied in Yamashiro et al 2003). The purpose of the cementum, which is a thin layer of mineralised tissue, is to attach the periodontal ligament in the gingiva to the surface of the root (Smid et al 2004)

One of the final stages of tooth development is the eruption of the tooth. Studies were carried out on rat incisor teeth which showed that when the incisor tooth erupted, IGF-1 was expressed in the odontoblasts and ameloblasts, as well as its receptor (Joseph et al 1993, 1994, 1996 citied in Fukunaga et al 2008). Thus the evidence suggests that IGF-1 is needed during the final stages of the amelogenesis and dentinogenesis.

A major limitation within the researching of the papers was the fact that experiments and studies were carried out on rat teeth. Thus, there teeth are not the same to human teeth. Moreover, a small proportion of the papers were based on human teeth, were the study was carried out on teeth belonging to people with a defect (for example Fukunaga et al 2008 had their study carried out on a patient with leprechaunism). However, from researching the papers, it is evident that GH or GH-like molecules (like IGF-1 and BMP 2 and 4) are present within the different stages of odontogenesis, depicts the lack of information relating to human teeth. Evidence has shown that expression during various stages of tooth development. Furthermore, when there is a deficiency of GH, there are changes within the tooth structure when erupted. Thus, I can conclude that GH does play a role in tooth development, in particular during the tooth germ stages, amelogenesis and dentinogenesis. However, more research needs to be conducted to clearly show GH expression and its role in human teeth during its development pre and postnatal.

Tooth development is the process where teeth are formed from the developing tooth bud, growing and maturing until it erupts into the mouth. This process is known as odontogenesis. There are several stages to odontogenesis which include the development of the tooth bud and the formation of hard tissue (Thesleff 2006). Within this paper, I will be discussing whether growth hormone has an effect on the development of the tooth bud and formation of hard tissue (in particular enamel and dentine formation).

Growth hormone (GH) is produced by the pituitary gland, which is stimulated or inhibited by growth hormone releasing hormone (GHRH) and somatostatin respectively in the hypothalamus. GH stimulates the liver, for the production of insulin-like growth factor (IGF-1) (Laron et al citied by Laron Z. 2001); this has an effect on bones (particularly long bones) and muscles and other tissue growth. Gotz el al (2006) says that IGFs are ‘growth factors controlling pre- and post natal development and growth processes.’ Furthermore, IGF-1 and GH are able to induce bone morpogenic proteins (BMP) messenger RNA (mRNA), in particular BMP-2 and 4 mRNA(Li et al 1998). The study that was carried out showed that GH and IGF-1 increased the production of BMP-2 mRNA by up to 5-fold and BMP-4 mRNA by up to 4-fold.

In the developing tooth bud, there are four main stages; these include: the bud stage, the cap stage, the bell stage and crown stage.

Figure 1: A schematic drawing of the bud stage – the arrow shows the formation of the tooth bud (tb) within the dental lamina (dl) where dental mesenchyme (dm) has condensed around the tooth bud (Adapted from Joseph et al 1994)

dl

dm

The bud stage is the tooth bud appearance, however, there is no arrangement of the cells – figure 1 illustrates this stage showing that this stage is just a group of cells by the dental lamina. Li and colleagues (1998) carried out a study which showed that BMP-4 mRNA was present in the dental epithelium during this stage until the cap stage. This suggests that BMP-4 is needed for the cells so that they are able to combine and form the dental papilla from this unorganised arrangement. In addition to this, GH and its receptor was reported to be involved in allow process like ‘induction, epithelial-mesenchymal interactions, cellular proliferation’ (Zhang et al 1997). The study was able to show that GH was present at embryonic day 17/18 in the rat, which represents the bud stage of odontogenesis in the rat.

However, a study conducted by Zhang and colleagues (1992) brought up a very important point. This being that the pituitary gland is still forming when tooth bud formation occurs. Thus, if the gland is still forming, GH would not be able to play a role during the bud stage. Therefore, it is possible that a GH-like molecule might be involved during the bud stage; however, it has not been confirmed.

The cap stage is when ectomesenchymal cells combine and become the dental papilla. Additionally, the tooth bud begins to grow around the ectomesenchymal cells, combine producing a cap appearance and becomes the dental (or enamel) organ. Eventually the dental papilla will produce dentine (and pulp) and the enamel organ will produce enamel. It is shown that during the cap stage numerous cells of the dental epithelium and mesenchyme were intensely immunoreactive for GH (Zhang et al 1997). This suggests that GH is involved in the formation of the enamel organ and dental papilla, which are needed to form enamel and dentine respectively. Furthermore, studies (Joseph et al 1994) found out that GH receptors were Figure 2: A schematic drawing of the late cap stage showing the dental follicle (df) containing the dental/enamel organ and dental papilla (dp). The dental/enamel organ is starting to differentiate into the outer dental epithelium (ode) and inner dental epithelium (ide). (Adapted from Joseph et al 1994)

dp

expressed in the epithelium (where the enamel organ is located) and also in ectomesenchymal cells (where the dental papilla is located). Thus, showing that the receptors for GH are present indicating that GH is able to activate the receptors which are needed to activate the cells. This evidence both support the idea that GH is needed for the differentiation of ectomesenchymal cells to form the dental papilla and dental organ.

Figure Figure 3: A schematic drawing of the bell stage: Differentiation of the dental/enamel organ and dental papilla (dp) occurs. The enamel oragn differentiates into the outer dental epithelium (ode), inner dental epithelium (ide), stellate reticulum (sr) and stellate intermedium (si). The dental papilla differentiates into the outer and central mesenchymal cells of the dental/enamel organ.

The bell stage (named because the dental organ is shaped as a bell) is when histodifferentiation and morphodifferentiation of the dental papilla and enamel organ take place. Joseph and his colleagues (1994) showed that in the early period of the bell stage, there is growth of the dental organ, as cubical inner epithelium differentiates into columnar cells. Additionally, immunoreacitivity for GH receptor/binding protein found that the outer and inner enamel epithelium and stratum intermedium were positive, signifying that the growth hormone receptor is involved in the differentiation of the enamel organ. This in turn allows the inner enamel epithelium to differentiate into ameoblasts, outer enamel epithelium to provide a protective barrier during enamel production and finally, stratum intermedium is needed for enamel production to occur. However, the dental papilla and stellate reticulum were negative for immunoreactivity of GH receptor/binding protein. This suggests that dental papilla does not need GH to differentiate nor does the stellate reticulum which is needed as support for enamel production.

The tables below (table 1 and 2) summarises the immunoreactivity expression of growth hormone at various stages of tooth development, including the bud and cap stage. It is clearly shown that in the stages for developing tooth germ, GH, its receptor and binding protein are expressed in various cells throughout the stages.

Table : Immunoreactivity expressed in the epithelium of a embryonic rat mandible showing the presence of GH, GH receptor and GH binding protein during embryonic day 17, 16, 20/21 and post natal day 9. The results are recorded show the intensity of the expression: +++ STRONG, ++ MODERATE, + MILD & +/- EQUIVOCAL (Zhang et al 1997)

Table 2: Immunoreactivity expressed in the mesenchyme of a embryonic rat mandible showing the presence of GH, GH receptor and GH binding protein during embryonic day 17, 16, 20/21 and post natal day 9. The results are recorded show the intensity of the expression: +++ STRONG, ++ MODERATE, + MILD & +/- EQUIVOCAL (Zhang et al 1997)The finally stage of the developing tooth bud is the crown (or maturation) stage. This is when the hard tissue (enamel and dentine) start to develop. Thus, the inner enamel epithelial cells start to change shape and differentiate into ameloblasts and the dental papilla changes in both size and shape and differentiate into odontoblasts to form dentine. This leads to the two processes commonly known as amelogenesis (formation of enamel) and dentinogenesis (formation of dentine).

Symons et al (2000) showed that there immunoreactivity of the IGF-1 receptor present during the maturation of the ameloblasts. Thus, it indicates that IGF-1 (via its receptor) is involved during amelogenesis. This shows that IGF-1 is needed for the ameloblasts to remove organic material and water (Nanci et al 1987), with increased flux of calcium and phosphate ions (Borke et al 1993)

Caviedes-Bucheli et al (2009) study was investigating real time PCR in mouse pulp cultures. The found out that IGF-1 can enhance the mineralisation of enamel (& dentine). The way it was able to do this was by inducing expressions of specific genes (Caton et al 2005)

In addition to is, Caton et al (2005) was investigating the effect that IGF-1 would have on tooth development in vitro. The results showed that the samples treated with IGF-1 had an increased enamel extracellular matrix, when compared to the control samples. This shows that there is increased enamel and dentine when IGF-1 was present, indicating that IGF-1 has a positive effect on the enamel and dentine formation.

The majority of the studies show the presence of GH and its receptor within cells. Smid and colleagues (2007) carried out an experiment when mouse molar teeth had a GH deficiency. The results shows that when there is a deficiency the crown dimensions were affected as the total crown area and the mesiodistal width at the cement-enamel junction (CEJ) was significantly smaller, when compared to when GH was present. This indicates that GH is needed to ensure growth of the tooth enamel and dentine, and when there is a deficiency, it affected the size of molar teeth.

Crown formation is finished when the inner enamel epithelium and outer enamel epithelium forms a double layers of HERS. This starts to proliferate apically and starts root morphogenesis. Yamashiro et al (2003) found out that BMP-2, -3, -4 and -7 were expressed during root formation and was associated with the differentiation of hard tissues. In particular, BMP-4 and -7 were expressed in ameloblasts – which indicate that they are needed for formation of enamel. Furthermore, expression of BMP-4 was also noted in cementoblasts which is needed for the production of primary acellular cementum and secondary cellular cementum (where acellular cementum is found on the cervical third and middle of the roots and attaches to principle fibres in the periodontal ligament and cellular cementum is located on the apical third of the root – Cho & Grant 2000 citied in Yamashiro et al 2003). The purpose of the cementum, which is a thin layer of mineralised tissue, is to attach the periodontal ligament in the gingiva to the surface of the root (Smid et al 2004)

One of the final stages of tooth development is the eruption of the tooth. Studies were carried out on rat incisor teeth which showed that when the incisor tooth erupted, IGF-1 was expressed in the odontoblasts and ameloblasts, as well as its receptor (Joseph et al 1993, 1994, 1996 citied in Fukunaga et al 2008). Thus the evidence suggests that IGF-1 is needed during the final stages of the amelogenesis and dentinogenesis.

A major limitation within the researching of the papers was the fact that experiments and studies were carried out on rat teeth. Thus, there teeth are not the same to human teeth. Moreover, a small proportion of the papers were based on human teeth, were the study was carried out on teeth belonging to people with a defect (for example Fukunaga et al 2008 had their study carried out on a patient with leprechaunism). However, from researching the papers, it is evident that GH or GH-like molecules (like IGF-1 and BMP 2 and 4) are present within the different stages of odontogenesis, depicts the lack of information relating to human teeth. Evidence has shown that expression during various stages of tooth development. Furthermore, when there is a deficiency of GH, there are changes within the tooth structure when erupted. Thus, I can conclude that GH does play a role in tooth development, in particular during the tooth germ stages, amelogenesis and dentinogenesis. However, more research needs to be conducted to clearly show GH expression and its role in human teeth during its development pre and postnatal.

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