Effects of aFGF, bFGF, TGFβ1 and IGF‐I on odontoblast differentiation <i>in vitro</i>

Martín, Amaya; Unda, Fernando-José; Bègue-Kirn, Catherine; Ruch, J V; Aréchaga, Juan

doi:10.1111/j.1600-0722.1998.tb02162.x

Cited by 39 publications

(29 citation statements)

References 2 publications

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“…In agreement with earlier reports on the inductive effects of TGF-␤1 on differentiation of pulpal cells into odontoblasts (24,25) and also on vasculogenesis (26), we observed an apparent increase in pulpal cell mass and also differentiation into odontoblast-like cells in dTGF-␤1 teeth. In these transgenic mice, the dentinal tubules through which the DECM and other components are secreted to form dentin were disorganized and reduced in length as a result of improper polarization and alignment of odontoblasts (data not shown).…”

Section: Discussionsupporting

confidence: 82%

Reduced Expression of Dentin Sialophosphoprotein Is Associated with Dysplastic Dentin in Mice Overexpressing Transforming Growth Factor-β1 in Teeth

Thyagarajan

Sreenath

Cho

et al. 2001

Journal of Biological Chemistry

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Transforming growth factor (TGF)-␤1 is expressed in developing tooth from the initiation stage through adulthood. Odontoblast-specific expression of TGF-␤1 in the tooth continues throughout life; however, the precise biological functions of this growth factor in the odontoblasts are not clearly understood. Herein, we describe the generation of transgenic mice that overexpress active TGF-␤1 predominantly in the odontoblasts. Teeth of these mice show a significant reduction in the tooth mineralization, defective dentin formation, and a relatively high branching of dentinal tubules. Dentin extracellular matrix components such as type I and III collagens are increased and deposited abnormally in the dental pulp, similar to the hereditary human tooth disorders such as dentin dysplasia and dentinogenesis imperfecta. Calcium, one of the crucial inorganic components of mineralization, is also apparently increased in the transgenic mouse teeth. Most importantly, the expression of dentin sialophosphoprotein (dspp), a candidate gene implicated in dentinogenesis imperfecta II (MIM 125420), is significantly down-regulated in the transgenic teeth. Our results provide in vivo evidence suggesting that TGF-␤1 mediated expression of dspp is crucial for dentin mineralization. These findings also provide for the first time a direct experimental evidence indicating that decreased dspp gene expression along with the other cellular changes in odontoblasts may result in human hereditary dental disorders like dentinogenesis imperfecta II (MIM 125420) and dentin dysplasia (MIM 125400 and 125420).Mammalian development is a complex and highly orchestrated process that involves intricate cross-talk between growth factors and other regulatory molecules. These molecules interact with each other to induce specific molecular and cellular changes leading to organogenesis. Interactions between epithelium and mesenchyme are particularly crucial during the initiation of development of key organs such as teeth, skin, hair, mammary gland, and prostate (1). Tooth development is initiated by epithelial-mesenchymal interactions in the first branchial arch, and several transcription factors and growth factors are known to be expressed by dentin extracellular matrix (DECM)-producing 1 odontoblasts and enamel-producing ameloblasts during tooth development (2-5). Transforming growth factor-␤1 (TGF-␤1), a prototype of the TGF-␤ superfamily, is a multi-functional growth factor expressed in a wide variety of developing tissues from the early stages. The regulation of cell proliferation, differentiation, embryonic development, and apoptosis by TGF-␤1 is well established (6 -8). During mouse tooth development, TGF-␤1 is expressed initially in the oral epithelium at embryonic day 13, and later its expression extends into the mesenchymal compartment and then gets restricted to the ectomesenchymal layer (odontoblasts). The odontoblast-restricted expression of TGF-␤1 persists throughout life in the mice (9). Odontoblasts produce DECM from embryonic day 16 and subseq...

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Section: Discussionsupporting

confidence: 82%

Reduced Expression of Dentin Sialophosphoprotein Is Associated with Dysplastic Dentin in Mice Overexpressing Transforming Growth Factor-β1 in Teeth

Thyagarajan

Sreenath

Cho

et al. 2001

Journal of Biological Chemistry

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“…23 Moreover, TGF-beta1 stimulates Sema3A expression in the dental mesenchyme at the time of the initial nerve encounter with the tooth target field. TGF-beta1 expression arises at the onset of tooth morphogenesis, 55 and during dentinogenesis, 57 and it regulate Ngf and Nt3 mRNA expression in maxillary process cells in culture. 56 GF signaling regulates embryonic development and organogenesis.…”

Section: Sema3a As a Link Integrating Organogenesis And Innervationmentioning

confidence: 99%

Integration of tooth morphogenesis and innervation by local tissue interactions, signaling networks, and semaphorin 3A

Luukko

Kettunen

2016

Cell Adhesion & Migration

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The tooth, like many other organs, develops from both epithelial and mesenchymal tissues, and has proven to be a valuable tool with which to investigate organ formation and peripheral innervation. Tooth formation is regulated by local epithelial-mesenchymal tissue interactions, and is closely integrated with stereotypic dental nerve navigation and patterning. Recent analyses of the function and regulation of semaphorin 3A (SEMA3A) have shed light on the regulatory mechanisms that coordinate organogenesis and innervation at the tissue and molecular levels. In the tooth, SEM3A acts as a developmentally regulated secretory chemo-repellent, that controls tooth innervation during embryonic and postnatal development. The tooth germ governs its own innervation by a combination of local tissue interactions and SEMA3A expression. SEMA3A signaling, in turn, is controlled by a number of conserved signaling effectors, including TGF-b superfamily members, FGF, and WNT; all function in embryo and organ development, and are essential for tooth histo-morphogenesis. Thus, SEMA3A driven axon guidance is integrated into key odontogenic signaling networks, establishing this protein as a critical molecular tether between 2 distinct developmental processes (morphogenesis and sensory innervation), both of which are required to obtain a functional tooth.

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“…It is this increase in our knowledge of the events during development that has allowed for the manipulation of odontoblast differentiation from pulp cells, or up-regulation of existing odontoblast secretory activity by means of several combinations of growth factors, such as transforming growth factor-13 (TGF-f3s) (Tziafas and Papadimitriou, 1998;, at-fibroblast growth factor (FGF), 13-FGF (Martin et al, 1998), and bone morphogenetic proteins (BMPs) in vivo (Nakashima, 1990(Nakashima, , 1994, with the ultimate aim of therapeutically manipulating odontoblast differentiation and matrix secretion to effect and enhance tissue repair.…”

Section: (I) Introductionmentioning

confidence: 99%

Proteoglycans in Dentinogenesis

Embery

Hall

Waddington

et al. 2001

Critical Reviews in Oral Biology & Medicine

169

158

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The predominant proteoglycans present in predentin and dentin are the chondroitin-sulphate-rich decorin and biglycan and the keratan-sulphate-rich lumican and fibromodulin. These are small, interstitial, leucine-rich proteoglycans which have recently been shown to exist in gradients across the predentin. Antibodies recognizing chondroitin sulphate show a decreasing gradient from the pulpal aspect toward the mineralizing front, the converse being true for keratan sulphate. Antidecorin shows an increase toward the mineralization front. Evidence from biochemical, autoradiographic, and immunohistochemical studies implies that such changes may be brought about by gradients of metalloproteinases. This offers the possibility that the proteoglycans organize the collagen network for receipt of phosphoproteins and phospholipids, the former being evident only at the onset of dentin formation. The suggestion is raised that glycosaminoglycan-depleted leucine-rich protein cores act as sequester points for receipt of phosphoproteins in particular. The rigid, spatially oriented glycosaminoglycan chains on decorin and biglycan are known to bind calcium and may feature directly in mineral initiation.Key words. Dentinogenesis, proteoglycans, phosphoconjugates, metalloproteinases, mineralization.(I) Introduction Jn recent years, there has been a wealth of new information on the group of non-collagenous glycoconjugates present in the extracellular matrix of most connective tissues, termed proteoglycans (PGs). These molecules are deemed to play structural and metabolic functional roles in both the soft and mineralized tissues of the body and are present in a wide variety of non-vertebrate and vertebrate species.Their presence in mineralized tissues, such as bone, has been evident for some time. Although the presence of PGs in predentin and, to a lesser extent, in dentin is well-established, it is only with the advent of contemporary biochemical and immunohistochemical procedures that their speciation, ultrastructural distribution, and possible biological roles in dentinogenesis are beginning to be elucidated.Within the last decade, there have been few reviews specifically addressing the function of PGs in relation to dentinogenesis. Research in this field has borrowed much of its knowledge from connective tissues in general, particularly the work on the aggregating PGs, such as aggrecan, present in cartilage. It The aspect of gradient distribution will be described in detail later and is of major significance, since it offers a functionality for such molecules during the structural transition of the extracellular matrix (ECM) of predentin, leading to the correct spatial assembly of the collagenous-non-coliagenous scaffold as a prelude for mineral deposition. For this reason, the review wili also deal with recent work on the potential of metalioproteinases (MMPs) to bring about such transition and the presence of phosphoprotein in dentin specifically hnked to mineralization. The absence of phosphoprotein from predentin an...

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Effects of aFGF, bFGF, TGFβ1 and IGF‐I on odontoblast differentiation in vitro

Cited by 39 publications

References 2 publications

Reduced Expression of Dentin Sialophosphoprotein Is Associated with Dysplastic Dentin in Mice Overexpressing Transforming Growth Factor-β1 in Teeth

Reduced Expression of Dentin Sialophosphoprotein Is Associated with Dysplastic Dentin in Mice Overexpressing Transforming Growth Factor-β1 in Teeth

Integration of tooth morphogenesis and innervation by local tissue interactions, signaling networks, and semaphorin 3A

Proteoglycans in Dentinogenesis

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