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Ugo Ripamonti - One of the best experts on this subject based on the ideXlab platform.
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Developmental pathways of periodontal tissue regeneration: Developmental diversities of tooth morphogenesis do also map capacity of periodontal tissue regeneration?
Journal of Periodontal Research, 2018Co-Authors: Ugo RipamontiAbstract:: 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-β3 (TGF-β3 ) 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-β3 and osteocalcin with fine-tuning and regulation of bone morphogenetic proteins BMP-2 and BMP-7, and upregulation of TGF-β3 . TGF-β3 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-β3 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 previously unknown. The appearance of cementum facing a vascularized and innervated periodontal ligament space with Sharpey's fibres inserting on to mineralized cementum provides a multiform pleiotropic masticatory apparatus adapted to multiple biting and lacerating forces as well as finely tuned and controlled forces beyond mastication and deglutition. The remarkable Cementogenesis as seen in stem mammals but particularly in mosasaurs with cemental trabeculations across the ligament space invocates the developmental capacity of cementum. The large cemental trabeculations as seen in mosasaurs and the cemental growth in stem mammals, together with regenerating scenarios in P. ursinus with large seams of cellular cementum and cementoid populated by contiguous cementoblasts indicate the continuous molecular cross-talk between cementum, newly formed cementoid matrix, cementoblasts and extracellular matrix soluble molecular signals. This molecular cross-talk may control the biomolecular homeostasis of both cementum and periodontal ligament, including angiogenesis. A further molecular scenario is invocated by the tight and exquisite anatomical relationships between the cementoid surfaces and the newly formed capillaries. The primitiveness of the craniate masticatory mineralized craniofacial apparatus has been controlled by several yet ancestral common genes not lastly the TGF-β3 gene. The TGF-β3 might have been responsible for the induction of Cementogenesis not only in extant P. ursinus but also in Diatectomorpha and mosasaurs, thus providing continuous evolutionary mechanisms for the induction of tissue morphogenesis across animal phyla for almost a billion years of evolution, epitomizing Nature's parsimony in controlling tissue induction and morphogenesis. TGF-β receptor II regulates osterix expression via Smad-dependent pathways indicating that TGF-β signalling acts as an upstream regulator of osterix during cementoblast differentiation. The presence of morphogenetic signals within the cemental matrix capable of inducing bone formation needs now to be assigned: bone induction initiated by extracted and partially purified cemental matrices may be the result of a slow release of embryonic remnants of osteogenic signals required and deployed during Cementogenesis. The cementum may thus rule the periodontal ligament space homeostasis, remodelling and repair by releasing sequestered morphogenetic signals that were deployed during embryogenesis.
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Cementogenesis and osteogenesis in periodontal tissue regeneration by recombinant human transforming growth factor- β 3 : a pilot study in Papio ursinus
Journal of Clinical Periodontology, 2017Co-Authors: Ugo Ripamonti, Ruqayya Parak, Roland M. Klar, Caroline Dickens, Therese Dix-peek, Raquel DuarteAbstract:Ripamonti U, Parak R, Klar RM, Dickens C, Dix-Peek T, Duarte R. Cementogenesis and osteogenesis in periodontal tissue regeneration by recombinant human transforming growth factor-b 3 : a pilot study in Papio ursinus. Abstract Objectives: The aim of this study was to investigate Cementogenesis and alveolar bone induction during in vivo periodontal tissue regeneration upon implantation of hTGF-b 3 in furcation defects of Papio ursinus and to evaluate the feasibility of gene expression studies. Materials and Methods: Class II furcation defects (day 0) were prepared in mandibular first and second molars of three P. ursinus and on day 30 implanted with and without 75 lg hTGF-b 3 in Matrigel Ò matrix. On day 0, 30 and 90, cementum and alveolar bone were harvested for gene expression analyses. Coral-derived bioreactors with and without 250 lg hTGF-b 3 were implanted in the rec-tus abdominis to monitor tissue induction. Results: hTGF-b 3 induced Cementogenesis with TGF-b 3 , Cementum Protein-1 (Cemp1) and Osteocalcin (OC) up-regulation, and down-regulation of BMP-2 and OP-1. Matrigel Ò matrix specimens showed up-regulation of BMP-2, TGF-b 3 , and
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Cementogenesis and osteogenesis in periodontal tissue regeneration by recombinant human transforming growth factor β3 a pilot study in papio ursinus
Journal of Clinical Periodontology, 2017Co-Authors: Ugo Ripamonti, Ruqayya Parak, Roland M. Klar, Caroline Dickens, Therese Dixpeek, Raquel DuarteAbstract:Objectives To investigate Cementogenesis and alveolar bone induction during in vivo periodontal tissue regeneration upon implantation of hTGF-β3 in furcation defects of Papio ursinus and to evaluate the feasibility of gene expression studies. Materials and Methods Class II furcation defects (day 0) were prepared in mandibular first and second molars of three P. ursinus and on day 30 implanted with and without 75μg hTGF-β3 in Matrigel®matrix. On day 0, 30 and 90, cementum and alveolar bone were harvested for gene expression analyses. Coral-derived bioreactors with and without 250μg hTGF-β3 were implanted in the rectus abdominis to monitor tissue induction. Results hTGF-β3 induced Cementogenesis with TGF-β3, Cementum Protein-1 (Cemp1) and Osteocalcin (OC) up-regulation, and down-regulation of BMP-2 and OP-1. Matrigel®matrix specimens showed up-regulation of BMP-2, TGF-β3, and OC, with down-regulation of OP-1 and Cemp1. hTGF-β3 induced alveolar bone with down-regulation of OP-1, TGF-β3, OC, and Cemp1. hTGF-β3 bioreactors induced bone at the periphery only. BMP-3, BMP-4, TGF-β1 and TGF-β3 were up-regulated in the adjacent muscle with TGF-β2 downregulation. Conclusions Cementogenesis and osteogenesis by hTGF-β3 entail the expression and up-regulation of TGF-β3, OC with fine tuning and modulation of BMP-2 and OP-1. This article is protected by copyright. All rights reserved.
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Redefining the induction of periodontal tissue regeneration in primates by the osteogenic proteins of the transforming growth factor‐β supergene family
Journal of Periodontal Research, 2016Co-Authors: Ugo RipamontiAbstract:The molecular bases of periodontal tissue induction and regeneration are the osteogenic proteins of the transforming growth factor-β (TGF-β) supergene family. These morphogens act as soluble mediators for the induction of tissues morphogenesis sculpting the multicellular mineralized structures of the periodontal tissues with functionally oriented ligament fibers into newly formed cementum. Human TGF-β3 (hTGF-β3) in growth factor-reduced Matrigel® matrix induces Cementogenesis when implanted in class II mandibular furcation defects surgically prepared in the non-human primate Chacma baboon, Papio ursinus. The newly formed periodontal ligament space is characterized by running fibers tightly attached to the cementoid surface penetrating as mineralized constructs within the newly formed cementum assembling and initiating within the mineralized dentine. Angiogenesis heralds the newly formed periodontal ligament space, and newly sprouting capillaries are lined by cellular elements with condensed chromatin interpreted as angioblasts responsible for the rapid and sustained induction of angiogenesis. The inductive activity of hTGF-β3 in Matrigel® matrix is enhanced by the addition of autogenous morcellated fragments of the rectus abdominis muscle potentially providing myoblastic, pericytic/perivascular stem cells for continuous tissue induction and morphogenesis. The striated rectus abdominis muscle is endowed with stem cell niches in para/perivascular location, which can be dominant, thus imposing stem cell features or stemness to the surrounding cells. This capacity to impose stemness is morphologically shown by greater alveolar bone induction and Cementogenesis when hTGF-β3 in Matrigel® matrix is combined with morcellated fragments of autogenous rectus abdominis muscle. The induction of periodontal tissue morphogenesis develops as a mosaic structure in which the osteogenic proteins of the TGF-β supergene family singly, synergistically and synchronously initiate and maintain tissue induction and morphogenesis. In primates, the presence of several homologous yet molecularly different isoforms with osteogenic activity highlights the biological significance of this apparent redundancy and indicates multiple interactions during embryonic development and bone regeneration in postnatal life. Molecular redundancy with associated different biological functionalities in primate tissues may simply represent the fine-tuning of speciation-related molecular evolution in anthropoid apes at the early Pliocene boundary, which resulted in finer tuning of the bone induction cascade.
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Bone morphogenetic proteins, Cementogenesis, myoblastic stem cells and the induction of periodontal tissue regeneration.
Cytokine & growth factor reviews, 2009Co-Authors: Ugo Ripamonti, Jeanclaude PetitAbstract:'Bone: Formation by autoinduction', initiates by invocation of soluble molecular signals which, when combined to insoluble signals or substrata trigger the ripple-like cascade of bone differentiation by induction. The osteogenic proteins of the transforming growth factor-beta (TGF-beta) superfamily, the bone morphogenetic/osteogenic proteins (BMPs/OPs), and uniquely in the non-human primate Papio ursinus also the three mammalian TGF-beta isoforms, induce endochondral bone formation as recapitulation of embryonic development. The pleiotropic activities of the BMPs/OPs are vast and include the induction of periodontal tissue regeneration. Implantation of naturally derived highly purified osteogenic fractions after sequential adsorption/affinity and gel filtration chromatography in mandibular Class II furcation defects of P. ursinus induces Cementogenesis as highly cellular collagenic cementoid attached to the exposed dentine with foci of nascent mineralization with inserted de novo generated Sharpey's fibres. Recombinant human osteogenic protein-1 (hOP-1) when implanted in Class II furcation defects of P. ursinus with surgically exposed dentine matrix preferentially initiates the induction of Cementogenesis; on the other hand, hBMP-2 preferentially induces alveolar bone regeneration with mineralized bone covered by prominent osteoid seams. Long-term studies with gamma-irradiated 0.5 and 2.5mg hOP-1 per gram of xenogeneic bovine collagenous matrix induce the restitutio ad integrum of the periodontal tissues in furcation defects exposed by chronic periodontitis in P. ursinus. A challenging question for tissue engineering and regenerative medicine is whether the presence of molecularly different osteogenic proteins of the TGF-beta superfamily has a therapeutic significance. Mechanistically, the specificity of hOP-1 primarily initiating Cementogenesis in periodontal defects is regulated by both the dentine extracellular matrix upon which responding cells attach and differentiate, and the structure/activity profile of the implanted hOP-1; the limited induction of Cementogenesis by hBMP-2 in furcation defects of non-human primate and canine models is consistent with the reported data that hBMP-2 inhibits differentiation and mineralization of cementoblasts in vitro aside the specific structure/activity profile of the implanted hBMP-2 protein. The induction of periodontal tissue regeneration develops as a mosaic structure in which the osteogenic proteins of the TGF-beta superfamily singly, synergistically and synchronously initiate and maintain tissue induction and morphogenesis as a recapitulation of embryonic development.
Tsuneyuki Yamamoto - One of the best experts on this subject based on the ideXlab platform.
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hertwig s epithelial root sheath fate during initial cellular Cementogenesis in rat molars
Acta Histochemica Et Cytochemica, 2015Co-Authors: Tsuneyuki Yamamoto, Tamaki Yamada, Tomomaya Yamamoto, Tomoka Hasegawa, Hiromi Hongo, Norio AmizukaAbstract:To elucidate the fate of the epithelial root sheath during initial cellular Cementogenesis, we examined developing maxillary first molars of rats by immunohistochemistry for keratin, vimentin, and tissue non-specific alkaline phosphatase (TNALP) and by TdT-mediated dUTP nick end labeling (TUNEL). The advancing root end was divided into three sections, which follow three distinct stages of initial cellular Cementogenesis: section 1, where the epithelial sheath is intact; section 2, where the epithelial sheath becomes fragmented; and section 3, where initial cellular Cementogenesis begins. After fragmentation of the epithelial sheath, many keratin-positive epithelial sheath cells were embedded in the rapidly growing cellular cementum. A few unembedded epithelial cells located on the cementum surface. Dental follicle cells, precementoblasts, and cementoblasts showed immunoreactivity for vimentin and TNALP. In all three sections, there were virtually no cells possessing double immunoreactivity for vimentin-keratin or TNALP-keratin and only embedded epithelial cells showed TUNEL reactivity. Taken together, these findings suggest that: (1) epithelial sheath cells divide into two groups; one group is embedded in the cementum and thereafter dies by apoptosis, and the other survives on the cementum surface as epithelial cell rests of Malassez; and (2) epithelial sheath cells do not undergo epithelial-mesenchymal transition during initial cellular Cementogenesis.
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Hertwig’s epithelial root sheath cell behavior during initial acellular Cementogenesis in rat molars
Histochemistry and Cell Biology, 2014Co-Authors: Tsuneyuki Yamamoto, Tamaki Yamada, Tomomaya Yamamoto, Tomoka Hasegawa, Hiromi Hongo, Norio AmizukaAbstract:This study was designed to examine developing acellular cementum in rat molars by immunohistochemistry, to elucidate (1) how Hertwig’s epithelial root sheath disintegrates and (2) whether epithelial sheath cells transform into cementoblasts through epithelial–mesenchymal transition (EMT). Initial acellular Cementogenesis was divided into three developmental stages, which can be seen in three different portions of the root: portion 1, where the epithelial sheath is intact; portion 2, where the epithelial sheath becomes fragmented; and portion 3, where acellular Cementogenesis begins. Antibodies against three kinds of matrix proteinases, which degrade epithelial sheath-maintaining factors, including basement membrane and desmosomes, were used to investigate proteolytic activity of the epithelial sheath. Tissue non-specific alkaline phosphatase (TNALP) and keratin were used to investigate EMT. Epithelial sheath cells showed immunoreactivity for all three enzymes at fragmentation, which suggests that epithelial sheath disintegration is enzymatically mediated. Dental follicle cells and cementoblasts showed intense immunoreactivity for TNALP, and from portion 1 through to 3, the reaction extended from the alveolar bone-related zone to the root-related zone. Cells possessing keratin/TNALP double immunoreactivity were virtually absent. Keratin-positive epithelial sheath cells showed negligible immunoreactivity for TNALP, and epithelial cells did not appear to migrate to the dental follicle. Together, these findings suggest that a transition phenotype between epithelial cells and cementoblasts does not exist in the developing dental follicle and hence that epithelial sheath cells do not undergo EMT during initial acellular Cementogenesis. In brief, this study supports the notion that cementoblasts derive from the dental follicle.
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hertwig s epithelial root sheath cell behavior during initial acellular Cementogenesis in rat molars
Histochemistry and Cell Biology, 2014Co-Authors: Tsuneyuki Yamamoto, Tamaki Yamada, Tomomaya Yamamoto, Tomoka Hasegawa, Hiromi Hongo, Norio AmizukaAbstract:This study was designed to examine developing acellular cementum in rat molars by immunohistochemistry, to elucidate (1) how Hertwig’s epithelial root sheath disintegrates and (2) whether epithelial sheath cells transform into cementoblasts through epithelial–mesenchymal transition (EMT). Initial acellular Cementogenesis was divided into three developmental stages, which can be seen in three different portions of the root: portion 1, where the epithelial sheath is intact; portion 2, where the epithelial sheath becomes fragmented; and portion 3, where acellular Cementogenesis begins. Antibodies against three kinds of matrix proteinases, which degrade epithelial sheath-maintaining factors, including basement membrane and desmosomes, were used to investigate proteolytic activity of the epithelial sheath. Tissue non-specific alkaline phosphatase (TNALP) and keratin were used to investigate EMT. Epithelial sheath cells showed immunoreactivity for all three enzymes at fragmentation, which suggests that epithelial sheath disintegration is enzymatically mediated. Dental follicle cells and cementoblasts showed intense immunoreactivity for TNALP, and from portion 1 through to 3, the reaction extended from the alveolar bone-related zone to the root-related zone. Cells possessing keratin/TNALP double immunoreactivity were virtually absent. Keratin-positive epithelial sheath cells showed negligible immunoreactivity for TNALP, and epithelial cells did not appear to migrate to the dental follicle. Together, these findings suggest that a transition phenotype between epithelial cells and cementoblasts does not exist in the developing dental follicle and hence that epithelial sheath cells do not undergo EMT during initial acellular Cementogenesis. In brief, this study supports the notion that cementoblasts derive from the dental follicle.
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hertwig s epithelial root sheath cells do not transform into cementoblasts in rat molar Cementogenesis
Annals of Anatomy-anatomischer Anzeiger, 2009Co-Authors: Tsuneyuki Yamamoto, Shigeru TakahashiAbstract:Summary It is generally accepted that cementoblasts originate in the process of differentiation of the mesenchymal cells of the dental follicle. Recently, a different hypothesis for the origin of cementoblasts has been proposed. Hertwig's epithelial root sheath cells undergo the epithelial–mesenchymal transformation to differentiate into cementoblasts. To elucidate whether the epithelial–mesenchymal transformation occurs in the epithelial sheath, developing rat molars were examined by keratin–vimentin and Runx2 (runt-related transcription factor 2)–keratin double immunostaining. In both acellular and cellular Cementogenesis, epithelial sheath and epithelial cells derived from the epithelial sheath expressed keratin, but did not express vimentin or Runx2. Dental follicle cells and cementoblasts, however, expressed vimentin and Runx2, but did not express keratin. No cells showed coexisting keratin–vimentin or Runx2–keratin staining. These findings suggest that there is no intermediate phenotype transforming epithelial to mesenchymal cells, and that epithelial sheath cells do not generate mineralized tissue. This study concludes that the epithelial–mesenchymal transformation does not occur in Hertwig's epithelial root sheath in rat acellular or cellular Cementogenesis and that the dental follicle is the origin of cementoblasts, as has been proposed in the original hypothesis.
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Mineralization process during acellular Cementogenesis in rat molars: a histochemical and immunohistochemical study using fresh-frozen sections
Histochemistry and Cell Biology, 2007Co-Authors: Tsuneyuki Yamamoto, Takanori Domon, Shigeru Takahashi, Khan Ara Yasmin Anjuman, Chifumi Fukushima, Minoru WakitaAbstract:This study was designed to detect tissue non-specific alkaline phosphatase (TNSALP) by Azo-dye staining, calcium by glyoxal bis (2-hydroxyanil) (GBHA) staining, bone sialoprotein (BSP) and osteopontin (OPN) by immunoperoxidase staining in developing rat molars, and also to discuss the mineralization process during acellular Cementogenesis. To restrain a reduction in histochemical and immunohistochemical reactions, fresh-frozen undemineralized sections were prepared. Where the epithelial sheath was intact, TNSALP reaction was observed in the dental follicle, but not in the epithelial sheath. With the onset of dentin mineralization, the BSP- and OPN-immunoreactive, initial cementum layer appeared. At this point, cementoblasts had shown intense TNSALP reaction and GBHA reactive particles (=calcium-GBHA complex) appeared on the root surface. With further development, the reaction of TNSALP and GBHA became weak on the root surface. Previous studies have shown that the initial cementum is fibril-poor and that matrix vesicles and calciferous spherules appear on the root surface only during the initial Cementogenesis. The findings mentioned above suggest that: during the initial Cementogenesis, cementoblasts release matrix vesicles which result in calciferous spherules, corresponding to the GBHA reactive particles. The calciferous spherules trigger the mineralization of the initial cementum. After principal fiber attachment, mineralization advances along collagen fibrils without matrix vesicles.
Martha J. Somerman - One of the best experts on this subject based on the ideXlab platform.
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overlapping functions of bone sialoprotein and pyrophosphate regulators in directing Cementogenesis
Bone, 2017Co-Authors: M Ao, Martha J. Somerman, Jose Luis Millan, M B Chavez, K C Hemstreet, Manisha C Yadav, L W Fisher, Harvey A Goldberg, Brian L. FosterAbstract:Abstract Although acellular cementum is essential for tooth attachment, factors directing its development and regeneration remain poorly understood. Inorganic pyrophosphate (PP i ), a mineralization inhibitor, is a key regulator of cementum formation: tissue-nonspecific alkaline phosphatase ( Alpl /TNAP) null mice (increased PP i ) feature deficient cementum, while progressive ankylosis protein ( Ank /ANK) null mice (decreased PP i ) feature increased cementum. Bone sialoprotein ( Bsp /BSP) and osteopontin ( Spp1 /OPN) are multifunctional extracellular matrix components of cementum proposed to have direct and indirect effects on cell activities and mineralization. Studies on dentoalveolar development of Bsp knockout ( Bsp −/− ) mice revealed severely reduced acellular cementum, however underlying mechanisms remain unclear. The similarity in defective cementum phenotypes between Bsp −/− mice and Alpl −/− mice (the latter featuring elevated PP i and OPN), prompted us to examine whether BSP is operating by modulating PP i -associated genes. Genetic ablation of Bsp caused a 2-fold increase in circulating PP i , altered mRNA expression of Alpl , Spp1 , and Ank , and increased OPN protein in the periodontia. Generation of a Bsp knock-out (KO) cementoblast cell line revealed significantly decreased mineralization capacity, 50% increased PP i in culture media, and increased Spp1 and Ank mRNA expression. While addition of 2 μg/ml recombinant BSP altered Spp1 , Ank , and Enpp1 expression in cementoblasts, changes resulting from this dose were not dependent on the integrin-binding RGD motif or MAPK/ERK signaling pathway. Decreasing PP i by genetic ablation of Ank on the Bsp −/− mouse background reestablished cementum formation, allowing > 3-fold increased acellular cementum volume compared to wild-type (WT). However, deleting Ank did not fully compensate for the absence of BSP. Bsp −/− ; Ank −/− double-deficient mice exhibited mean 20–27% reduced cementum thickness and volume compared to Ank −/− mice. From these data, we conclude that the perturbations in PP i metabolism are not solely driving the cementum pathology in Bsp −/− mice, and that PP i is more potent than BSP as a cementum regulator, as shown by the ability to override loss of BSP by lowering PP i . We propose that BSP and PP i work in concert to direct mineralization in cementum and likely other mineralized tissues.
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counter regulatory phosphatases tnap and npp1 temporally regulate tooth root Cementogenesis
International Journal of Oral Science, 2015Co-Authors: Laura E Zweifler, Martha J. Somerman, Mudita K Patel, Francisco H Nociti, Helen F Wimer, Jose Luis Millan, Brian L. FosterAbstract: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). The focus of this study was to define the roles of these phosphatases in Cementogenesis. 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.
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Counter-regulatory phosphatases TNAP and NPP1 temporally regulate tooth root Cementogenesis
International Journal of Oral Science, 2015Co-Authors: Laura E Zweifler, Martha J. Somerman, Mudita K Patel, Francisco H Nociti, Helen F Wimer, Jose Luis Millan, Brian L. FosterAbstract: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 (P_i) to mineral inhibitor pyrophosphate (PP_i), where local P_i and PP_i concentrations are controlled by phosphatases including tissue-nonspecific alkaline phosphatase (TNAP) and ectonucleotide pyrophosphatase/phosphodiesterase 1 (NPP1). The focus of this study was to define the roles of these phosphatases in Cementogenesis. 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 PP_i environment promoting acellular cementum initiation, while later NPP1 expression increases PP_i, restricting acellular cementum apposition. Alterations in PP_i have little effect on cellular cementum formation, though matrix mineralization is affected. The timing and site of action of two key enzymes help regulate the formation of cementum, one of the mineralized substances of teeth. An international team led by Brian Foster from the US National Institute of Arthritis and Musculoskeletal and Skin Diseases considered the roles of two enzymes — tissue non-specific phosphatase (TNAP) and ectonucleotide pyrophosphatase/phosphodiesterase 1 (NPP1) — in cementum development. They showed in mice that early TNAP expression created a particular environment in teeth with low levels of pyrophosphate, a mineral inhibitor. This promoted the creation of a type of cementum that does not incorporate cells into its structure. Later on in development, the expression of NPP1 boosted levels of pyrophosphate, which restricted this type of cementum. These enzymes had little effect on cementum containing cells. The researchers confirmed these patterns in extracted human teeth.
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genetic evidence for the vital function of osterix in Cementogenesis
Journal of Bone and Mineral Research, 2012Co-Authors: Hua Zhang, Martha J. Somerman, Yin Xiao, Xin Zhou, Benoit De Crombrugghe, Jian Q. FengAbstract:To date, attempts to regenerate a complete tooth, including the critical periodontal tissues associated with the tooth root, have not been successful. Controversy still exists regarding the origin of the cell source for cellular cementum (epithelial or mesenchymal). This disagreement may be partially due to a lack of understanding of the events leading to the initiation and development of the tooth roots and supportive tissues, such as the cementum. Osterix (OSX) is a transcriptional factor essential for osteogenesis, but its role in Cementogenesis has not been addressed. In the present study, we first documented a close relationship between the temporal- and spatial-expression pattern of Osx and the formation of cellular cementum. We then generated 3.6-kilobase (kb) collagen type I (3.6-kb Col 1)-Osx transgenic mice, which displayed accelerated cementum formation versus wild-type (WT) controls. Importantly, the conditional deletion of Osx in the mesenchymal cells with two different Cre systems (the 2.3-kb Col 1 and an inducible CAG–Cre estrogen receptor [CreER]) led to a sharp reduction in cellular cementum formation (including the cementum mass and mineral deposition rate) and gene expression of dentin matrix protein 1 (DMP1) by cementocytes. However, the deletion of the Osx gene after cellular cementum formed did not alter the properties of the mature cementum as evaluated by backscattered scanning electron microscopy (SEM) and resin-casted SEM. Transient transfection of Osx in the cementoblasts in vitro significantly inhibited cell proliferation and increased cell differentiation and mineralization. Taken together, these data support: (1) the mesenchymal origin of cellular cementum (from periodontal ligament [PDL] progenitor cells); (2) the vital role of OSX in controlling the formation of cellular cementum; and (3) the limited remodeling of cellular cementum in adult mice. © 2012 American Society for Bone and Mineral Research.
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bone sialoprotein is localized to the root surface during Cementogenesis
Journal of Bone and Mineral Research, 2009Co-Authors: R L Macneil, C. Strayhorn, Larry W. Fisher, N Sheng, Martha J. SomermanAbstract:: Bone sialoprotein (BSP), an RGD-containing protein with cell attachment properties, is believed to play a regulatory role in the biomineralization of various connective tissues. To determine its possible role in tooth root formation, murine dentoalveolar tissues at sequential phases of development were analyzed immunohistochemically for the presence of BSP. BSP was localized to alveolar bone and cementum at time points associated with initial mineralization of these tissues. In addition, northern blot analyses of dental follicle tissue at day 27 of tooth development indicated that BSP mRNA is expressed by dental follicle cells at a time point coincident with the initiation of Cementogenesis on the peripheral tooth root surface. Collectively, these findings indicate that BSP may play an important role in the formation and mineralization of cementum.
Norio Amizuka - One of the best experts on this subject based on the ideXlab platform.
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hertwig s epithelial root sheath fate during initial cellular Cementogenesis in rat molars
Acta Histochemica Et Cytochemica, 2015Co-Authors: Tsuneyuki Yamamoto, Tamaki Yamada, Tomomaya Yamamoto, Tomoka Hasegawa, Hiromi Hongo, Norio AmizukaAbstract:To elucidate the fate of the epithelial root sheath during initial cellular Cementogenesis, we examined developing maxillary first molars of rats by immunohistochemistry for keratin, vimentin, and tissue non-specific alkaline phosphatase (TNALP) and by TdT-mediated dUTP nick end labeling (TUNEL). The advancing root end was divided into three sections, which follow three distinct stages of initial cellular Cementogenesis: section 1, where the epithelial sheath is intact; section 2, where the epithelial sheath becomes fragmented; and section 3, where initial cellular Cementogenesis begins. After fragmentation of the epithelial sheath, many keratin-positive epithelial sheath cells were embedded in the rapidly growing cellular cementum. A few unembedded epithelial cells located on the cementum surface. Dental follicle cells, precementoblasts, and cementoblasts showed immunoreactivity for vimentin and TNALP. In all three sections, there were virtually no cells possessing double immunoreactivity for vimentin-keratin or TNALP-keratin and only embedded epithelial cells showed TUNEL reactivity. Taken together, these findings suggest that: (1) epithelial sheath cells divide into two groups; one group is embedded in the cementum and thereafter dies by apoptosis, and the other survives on the cementum surface as epithelial cell rests of Malassez; and (2) epithelial sheath cells do not undergo epithelial-mesenchymal transition during initial cellular Cementogenesis.
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Hertwig’s epithelial root sheath cell behavior during initial acellular Cementogenesis in rat molars
Histochemistry and Cell Biology, 2014Co-Authors: Tsuneyuki Yamamoto, Tamaki Yamada, Tomomaya Yamamoto, Tomoka Hasegawa, Hiromi Hongo, Norio AmizukaAbstract:This study was designed to examine developing acellular cementum in rat molars by immunohistochemistry, to elucidate (1) how Hertwig’s epithelial root sheath disintegrates and (2) whether epithelial sheath cells transform into cementoblasts through epithelial–mesenchymal transition (EMT). Initial acellular Cementogenesis was divided into three developmental stages, which can be seen in three different portions of the root: portion 1, where the epithelial sheath is intact; portion 2, where the epithelial sheath becomes fragmented; and portion 3, where acellular Cementogenesis begins. Antibodies against three kinds of matrix proteinases, which degrade epithelial sheath-maintaining factors, including basement membrane and desmosomes, were used to investigate proteolytic activity of the epithelial sheath. Tissue non-specific alkaline phosphatase (TNALP) and keratin were used to investigate EMT. Epithelial sheath cells showed immunoreactivity for all three enzymes at fragmentation, which suggests that epithelial sheath disintegration is enzymatically mediated. Dental follicle cells and cementoblasts showed intense immunoreactivity for TNALP, and from portion 1 through to 3, the reaction extended from the alveolar bone-related zone to the root-related zone. Cells possessing keratin/TNALP double immunoreactivity were virtually absent. Keratin-positive epithelial sheath cells showed negligible immunoreactivity for TNALP, and epithelial cells did not appear to migrate to the dental follicle. Together, these findings suggest that a transition phenotype between epithelial cells and cementoblasts does not exist in the developing dental follicle and hence that epithelial sheath cells do not undergo EMT during initial acellular Cementogenesis. In brief, this study supports the notion that cementoblasts derive from the dental follicle.
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hertwig s epithelial root sheath cell behavior during initial acellular Cementogenesis in rat molars
Histochemistry and Cell Biology, 2014Co-Authors: Tsuneyuki Yamamoto, Tamaki Yamada, Tomomaya Yamamoto, Tomoka Hasegawa, Hiromi Hongo, Norio AmizukaAbstract:This study was designed to examine developing acellular cementum in rat molars by immunohistochemistry, to elucidate (1) how Hertwig’s epithelial root sheath disintegrates and (2) whether epithelial sheath cells transform into cementoblasts through epithelial–mesenchymal transition (EMT). Initial acellular Cementogenesis was divided into three developmental stages, which can be seen in three different portions of the root: portion 1, where the epithelial sheath is intact; portion 2, where the epithelial sheath becomes fragmented; and portion 3, where acellular Cementogenesis begins. Antibodies against three kinds of matrix proteinases, which degrade epithelial sheath-maintaining factors, including basement membrane and desmosomes, were used to investigate proteolytic activity of the epithelial sheath. Tissue non-specific alkaline phosphatase (TNALP) and keratin were used to investigate EMT. Epithelial sheath cells showed immunoreactivity for all three enzymes at fragmentation, which suggests that epithelial sheath disintegration is enzymatically mediated. Dental follicle cells and cementoblasts showed intense immunoreactivity for TNALP, and from portion 1 through to 3, the reaction extended from the alveolar bone-related zone to the root-related zone. Cells possessing keratin/TNALP double immunoreactivity were virtually absent. Keratin-positive epithelial sheath cells showed negligible immunoreactivity for TNALP, and epithelial cells did not appear to migrate to the dental follicle. Together, these findings suggest that a transition phenotype between epithelial cells and cementoblasts does not exist in the developing dental follicle and hence that epithelial sheath cells do not undergo EMT during initial acellular Cementogenesis. In brief, this study supports the notion that cementoblasts derive from the dental follicle.
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Cementogenesis and osteogenesis in periodontal tissue regeneration by recombinant human transforming growth factor- β 3 : a pilot study in Papio ursinus
Journal of Clinical Periodontology, 2017Co-Authors: Ugo Ripamonti, Ruqayya Parak, Roland M. Klar, Caroline Dickens, Therese Dix-peek, Raquel DuarteAbstract:Ripamonti U, Parak R, Klar RM, Dickens C, Dix-Peek T, Duarte R. Cementogenesis and osteogenesis in periodontal tissue regeneration by recombinant human transforming growth factor-b 3 : a pilot study in Papio ursinus. Abstract Objectives: The aim of this study was to investigate Cementogenesis and alveolar bone induction during in vivo periodontal tissue regeneration upon implantation of hTGF-b 3 in furcation defects of Papio ursinus and to evaluate the feasibility of gene expression studies. Materials and Methods: Class II furcation defects (day 0) were prepared in mandibular first and second molars of three P. ursinus and on day 30 implanted with and without 75 lg hTGF-b 3 in Matrigel Ò matrix. On day 0, 30 and 90, cementum and alveolar bone were harvested for gene expression analyses. Coral-derived bioreactors with and without 250 lg hTGF-b 3 were implanted in the rec-tus abdominis to monitor tissue induction. Results: hTGF-b 3 induced Cementogenesis with TGF-b 3 , Cementum Protein-1 (Cemp1) and Osteocalcin (OC) up-regulation, and down-regulation of BMP-2 and OP-1. Matrigel Ò matrix specimens showed up-regulation of BMP-2, TGF-b 3 , and
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Cementogenesis and osteogenesis in periodontal tissue regeneration by recombinant human transforming growth factor β3 a pilot study in papio ursinus
Journal of Clinical Periodontology, 2017Co-Authors: Ugo Ripamonti, Ruqayya Parak, Roland M. Klar, Caroline Dickens, Therese Dixpeek, Raquel DuarteAbstract:Objectives To investigate Cementogenesis and alveolar bone induction during in vivo periodontal tissue regeneration upon implantation of hTGF-β3 in furcation defects of Papio ursinus and to evaluate the feasibility of gene expression studies. Materials and Methods Class II furcation defects (day 0) were prepared in mandibular first and second molars of three P. ursinus and on day 30 implanted with and without 75μg hTGF-β3 in Matrigel®matrix. On day 0, 30 and 90, cementum and alveolar bone were harvested for gene expression analyses. Coral-derived bioreactors with and without 250μg hTGF-β3 were implanted in the rectus abdominis to monitor tissue induction. Results hTGF-β3 induced Cementogenesis with TGF-β3, Cementum Protein-1 (Cemp1) and Osteocalcin (OC) up-regulation, and down-regulation of BMP-2 and OP-1. Matrigel®matrix specimens showed up-regulation of BMP-2, TGF-β3, and OC, with down-regulation of OP-1 and Cemp1. hTGF-β3 induced alveolar bone with down-regulation of OP-1, TGF-β3, OC, and Cemp1. hTGF-β3 bioreactors induced bone at the periphery only. BMP-3, BMP-4, TGF-β1 and TGF-β3 were up-regulated in the adjacent muscle with TGF-β2 downregulation. Conclusions Cementogenesis and osteogenesis by hTGF-β3 entail the expression and up-regulation of TGF-β3, OC with fine tuning and modulation of BMP-2 and OP-1. This article is protected by copyright. All rights reserved.