TGF-β Signaling Regulates Cementum Formation through Osterix Expression

Choi, Hwajung; Ahn, Yu-Hyun; Kim, Tak-Heun; Bae, Cheol-Hyeon; Lee, Jeong-Chae; You, Hyung‐Keun; Cho, Eui-Sic

doi:10.1038/srep26046

Cited by 37 publications

(50 citation statements)

References 43 publications

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“…In this study, we adopted the immortalized cementoblast cell line (OOCM-30), which is a well-established and widely-recognized mature cementoblast cell line [17,23,24,25,26]. The OCCM-30 cell line was first isolated from OC-TAG (the SV40 large T-antigen (TAg) was integrated into the osteocalcin (OC) promoter) transgenic mice in Martha Somerman’s lab at the University of Michigan [27].…”

Section: Discussionmentioning

confidence: 99%

“…Conversely, exogenous BMP-7 could strongly upregulate cementoblastogenesis of mature cementoblast cells [39]. Furthermore, TGF-β signaling plays a major role as one of the upstream regulators of Osterix in cementoblast differentiation and cementum formation [25]. All of these data suggest that cementoblastogenesis is modulated by TGF-β/BMP in a more complicated manner than osteoblastogenesis.…”

Section: Discussionmentioning

confidence: 99%

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Screening the Expression Changes in MicroRNAs and Their Target Genes in Mature Cementoblasts Stimulated with Cyclic Tensile Stress

Wang

Cheng

et al. 2016

IJMS

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Cementum is a thin layer of cementoblast-produced mineralized tissue covering the root surfaces of teeth. Mechanical forces, which are produced during masticatory activity, play a paramount role in stimulating cementoblastogenesis, which thereby facilitates the maintenance, remodeling and integrity of cementum. However, hitherto, the extent to which a post-transcriptional modulation mechanism is involved in this process has rarely been reported. In this study, a mature murine cementoblast cell line OCCM-30 cells (immortalized osteocalcin positive cementoblasts) was cultured and subjected to cyclic tensile stress (0.5 Hz, 2000 µstrain). We showed that the cyclic tensile stress could not only rearrange the cell alignment, but also influence the proliferation in an S-shaped manner. Furthermore, cyclic tensile stress could significantly promote cementoblastogenesis-related genes, proteins and mineralized nodules. From the miRNA array analyses, we found that 60 and 103 miRNAs were significantly altered 6 and 18 h after the stimulation using cyclic tensile stress, respectively. Based on a literature review and bioinformatics analyses, we found that miR-146b-5p and its target gene Smad4 play an important role in this procedure. The upregulation of miR-146b-5p and downregulation of Smad4 induced by the tensile stress were further confirmed by qRT-PCR. The direct binding of miR-146b-5p to the three prime untranslated region (3′ UTR) of Smad4 was established using a dual-luciferase reporter assay. Taken together, these results suggest an important involvement of miR-146b-5p and its target gene Smad4 in the cementoblastogenesis of mature cementoblasts.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Screening the Expression Changes in MicroRNAs and Their Target Genes in Mature Cementoblasts Stimulated with Cyclic Tensile Stress

Wang

Cheng

et al. 2016

IJMS

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“…23 In contrast with the literature, this study found less STRO-1 expression near mineralized tissue, suggesting that these few stained cells have not yet undergone differentiation into osteoblasts or cementoblasts. OSX is a transcription factor with an important role in the differentiation of osteoblasts and cementoblasts 8,9 that occurs in odontogenesis and osteogenesis. 24 Tsiligkrou et al 25 investigated the expression of proteins in POF such as Runx-2, bone morphogenetic protein 2 (BMP-2), and cementum attachment protein (CAP).…”

Section: Discussionmentioning

confidence: 99%

The role of Osterix protein in the pathogenesis of peripheral ossifying fibroma

et al. 2017

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Peripheral ossifying fibroma (POF) is a reactive lesion of oral tissues, associated with local factors such as trauma or presence of dental biofilm. POF treatment consists of curettage of the lesion combined with root scaling of adjacent teeth and/or removal of other sources of irritants. This study aimed to analyze the clinical and pathological features of POF and to investigate the immunoexpression of Osterix and STRO-1 proteins. Data such as age, gender, and size were obtained from 30 cases of POF. Microscopic features were assessed by conventional light microscopy using hematoxylin-eosin staining and immunohistochemical markers, and by polarized light microscopy using Picrosirius red staining. The age range was 11-70 years and 70% of the patients were female. Moreover, the size of POF varied from 0.2 to 5.0 cm; in 43.33% of the cases, the mineralized content consisted exclusively of bony trabeculae. The immunohistochemical analysis showed nuclear staining for Osterix in 63% and for STRO-1 in 20% of the cases. Mature collagen fibers were observed in mineralized tissue in 76.67% of the cases. The clinical and microscopic features observed were in agreement with those described in the literature. Osterix was overexpressed, while STRO-1 was poorly expressed. Osterix was expressed particularly in cells entrapped in and around mineralized tissue, indicating the presence of a stimulus that triggers the differentiation of these cells into osteoblasts or cementoblasts, i.e., cells that produce mineralized tissue. Based on our results, Osterix may play a role in the pathogenesis of POF.

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“…However, OSX has been found to be a critical transcriptional factor not only in osteogenesis but also in cementogenesis. More recent data show that TGF‐β signalling regulates cementum formation via OSX expression . The studies showed that osteocalcin‐Cre ‐mediated Tgfbr2 ( OC Cre Tgfbr2 fl/fl ) conditional knockout mice molars, with no functional TGF‐β receptor II, have a profound reduction in cellular cementum together with limited or absent cementum synthesis and deposition .…”

Section: Developmental Induction Of Tooth Morphogenesis: Cementogenesmentioning

confidence: 99%

Developmental pathways of periodontal tissue regeneration

Ripamonti

2018

J of Periodontal Research

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Nothing is known on the impact of developmental divergence on periodontal tissue regeneration in vertebrate animals. Molecularly, the induction of tooth morphogenesis is highly conserved deploying across animal phyla a constant and reproducible set of gene pathways, which result in morphogenesis of multiple odontode forms and shapes. Genetic mutations positively affect animal speciation via evolving biting and masticatory forces as well as dietary habits selectively imprinted in animal phyla during evolutionary speciation. The geometry of the attachment apparatus of a tooth is important for the interpretation of the induction of cementogenesis with de novo Sharpey's fibres as in thecodonty, ie, a tripartite attachment of alveolar bone, periodontal ligament and cementum. This review addresses the tooth implantation in different animal clades from the fibrous attachment of the Elasmobranch Carcharinus obscurus dusky shark, reviewing the evolution and functional significance of cementum with functionally inserted Sharpey's fibres. In sharks there is a continuous tooth replacement mechanistically supported by the continuously erupting dental lamina. We show that the arching of the continuously erupting dental lamina, a critical step for the selachians' tooth differentiation, is prominently characterized by transforming growth factor-β (TGF-β ) expression not only within the dental lamina but also in cellular condensations in the mesenchymal tissues of the erupting tooth. Such findings indicate the pleiotropic multifaceted activity of a highly conserved mammalian gene across genera, masterminding tooth morphogenesis in both selachians and mammals as well as periodontal tissue induction in the non-human primate Papio ursinus. In P. ursinus, the induction of cementogenesis entails the expression of TGF-β and osteocalcin with fine-tuning and regulation of bone morphogenetic proteins BMP-2 and BMP-7, and upregulation of TGF-β . TGF-β autoinduction and upregulation during the induction of cementogenesis and osteogenesis in P. ursinus provide novel insights into the induction of cementogenesis. It is hypothesized that the evolutionary expression and upregulation of the TGF-β gene may provide the mechanistic insights into the induction of extensive cementogenesis as seen in stem mammals and the induction of trabecular-like cementum formation in mosasaurs' tooth attachment. Aspidin, the precursor of cementum, was reported to appear 310-330 million years ago (Ma) in Odontostraci armoured fish. Studies showed that the differentiation of cementum with inserted Sharpey's fibres is also present in lower amniotes such as Diatectomorpha or Diadectidae, the first herbivorous tetrapods, 323 Ma. In mosasaurs, 168-165 Ma, there is the induction of extensive trabeculation of cementum though nothing is known on the phylogenetic temporo-spatial evolution of cementum before Diadectidae and stem mammals. The large trabeculations of cementum as seen in the attachment of extinct mosasaurs invocates a pleiotropic capacity of cemental growth pre...

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TGF-β Signaling Regulates Cementum Formation through Osterix Expression

Cited by 37 publications

References 43 publications

Screening the Expression Changes in MicroRNAs and Their Target Genes in Mature Cementoblasts Stimulated with Cyclic Tensile Stress

Screening the Expression Changes in MicroRNAs and Their Target Genes in Mature Cementoblasts Stimulated with Cyclic Tensile Stress

The role of Osterix protein in the pathogenesis of peripheral ossifying fibroma

Developmental pathways of periodontal tissue regeneration

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