- Can non-collagenous proteins be employed for the differential diagnosis among fibrous dysplasia, cemento-osseous dysplasia and cemento-ossifying fibroma? [Journal Article]
- PRPathol Res Pract 2019; 215(7):152450
- Differential diagnosis among fibrous dysplasias, cemento-ossifying fibromas and cemento-osseous dysplasias is difficult, since there is considerable overlap of histologic features, but also extremely…
Differential diagnosis among fibrous dysplasias, cemento-ossifying fibromas and cemento-osseous dysplasias is difficult, since there is considerable overlap of histologic features, but also extremely important, since they differ greatly in etiology, clinical behaviour, prognosis and terapeuthic approach. There is no data about the use of immunohistochemistry, a viable and accessible technique, for this purpose. The objective of this study was to investigate, comparatively, the immunohistochemical expression of major non-collagenous proteins (osteonectin [ON], osteopontin [OP], bone sialoprotein [BSP] and osteocalcin [OC]) of mineralized tissue extracellular matrix in 22 cases of fibrous dysplasias, 16 of cemento-ossifying fibromas and 16 of cemento-osseous dysplasias. ON maintained the same expression profile in all cases; the staining for OP was negative in fusiform cells producing cementoid globules and weak, as well as heterogeneous, in high mineralized matrixes; there was negativity for BSP in cementoid globules and in the fusiform cells that produce them, differently from the strong positive expression found in the majority of bone trabeculae and their peripheral cuboidal osteoblasts; and finally, the immuno-reactivity for OC was weak, except in cuboidal osteoblasts and osteocytes. We can conclude that the nature of mineralized structure and the cellular phenotype are much more responsible for variability in immunohistochemical profile than the type of lesion (fibrous dysplasias, cemento-ossifying fibromas and cemento-osseous dysplasias) which makes difficult, at least for a while, the use of these proteins with diagnosis purpose.
- Developmental pathways of periodontal tissue regeneration: Developmental diversities of tooth morphogenesis do also map capacity of periodontal tissue regeneration? [Review]
- JPJ Periodontal Res 2019; 54(1):10-26
- 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 ac…
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.
- A Force on the Crown and Tug of War in the Periodontal Complex. [Review]
- JDJ Dent Res 2018; 97(3):241-250
- The load-bearing dentoalveolar fibrous joint is composed of biomechanically active periodontal ligament (PDL), bone, cementum, and the synergistic entheses of PDL-bone and PDL-cementum. Physiologic a…
The load-bearing dentoalveolar fibrous joint is composed of biomechanically active periodontal ligament (PDL), bone, cementum, and the synergistic entheses of PDL-bone and PDL-cementum. Physiologic and pathologic loads on the dentoalveolar fibrous joint prompt natural shifts in strain gradients within mineralized and fibrous tissues and trigger a cascade of biochemical events within the widened and narrowed sites of the periodontal complex. This review highlights data from in situ biomechanical simulations that provide tooth movements relative to the alveolar socket. The methods and subsequent results provide a reasonable approximation of strain-regulated biochemical events resulting in mesial mineral formation and distal resorption events within microanatomical regions at the ligament-tethered/enthesial ends. These biochemical events, including expressions of biglycan, decorin, chondroitin sulfated neuroglial 2, osteopontin, and bone sialoprotein and localization of various hypertrophic progenitors, are observed at the alkaline phosphatase-positive widened site, resulting in mineral formation and osteoid/cementoid layers. On the narrowed side, tartrate-resistant acid phosphatase regions can lead to a sequence of clastic activities resulting in resorption pits in bone and cementum. These strain-regulated biochemical and subsequently biomineralization events in the load-bearing periodontal complex are critical for maintenance of the periodontal space and overall macroscale joint biomechanics.
- Ameloblastic Fibro-odontoma with a Predominant Radiopaque Component. [Case Reports]
- AMAnn Maxillofac Surg 2017 Jul-Dec; 7(2):304-307
- Ameloblastic fibro-odontoma (AFO) is a rare odontogenic tumor. Initially believed to be a lesion similar to ameloblastic fibroma (AF), it is now considered as a separate entity in the WHO odontogenic…
Ameloblastic fibro-odontoma (AFO) is a rare odontogenic tumor. Initially believed to be a lesion similar to ameloblastic fibroma (AF), it is now considered as a separate entity in the WHO odontogenic tumor classification. Commonly associated with a painless swelling and an associated absence of eruption of a tooth, AFO presents as a mixed radiopaque and radiolucent lesion in the younger population with a predilection for the posterior region. Histologically, it shows the characteristics of an immature complex odontoma with irregularly arranged enamel, dentinoid, cementoid-like structures, and ectomesenchymal tissue. The following case report describes a case of AFO with a predominantly radiopaque component and briefly discusses the available literature pertaining to this rare entity.
- Histologic Findings of a Human Immature Revascularized/Regenerated Tooth with Symptomatic Irreversible Pulpitis. [Case Reports]
- JEJ Endod 2017; 43(6):905-909
- CONCLUSIONS: In the present case, regeneration of the pulplike tissue and the periodontium existed after a revascularization/regeneration procedure in an immature permanent tooth clinically diagnosed as symptomatic irreversible pulpitis.
- Conservative Management of Central Cemento-Ossifying Fibroma. [Case Reports]
- JCJ Craniofac Surg 2017; 28(1):e8-e9
- Central cemento-ossifying fibroma is characterized by the combined production of osteoid and cementoid tissue. Radiographically, this lesion is presented as an outlined cortical and variable radiopaq…
Central cemento-ossifying fibroma is characterized by the combined production of osteoid and cementoid tissue. Radiographically, this lesion is presented as an outlined cortical and variable radiopaque spots, also can be present complete radiolucent or different degrees of radiopacity. The recommended treatment is curettage or enucleation, and the recurrence rate is less than 5%. Considering that surgical treatment is invasive, mainly in large lesions, this study aims to report a patient in whom conservative treatment was carried out by involving the preservation of teeth, with a long-term follow-up. A 48-year-old black female patient, diagnosed with central cemento-ossifying fibroma in mandible, treated conservatively and a 2 years of follow-up. It was concluded that the conservative treatment with a long term of follow-up for maintaining teeth was satisfactory.
- The Cementocyte-An Osteocyte Relative? [Review]
- JDJ Dent Res 2016; 95(7):734-41
- Cementum is a mineralized tissue covering the tooth root that functions in tooth attachment and posteruptive adjustment of tooth position. During formation of the apically located cellular cementum, …
Cementum is a mineralized tissue covering the tooth root that functions in tooth attachment and posteruptive adjustment of tooth position. During formation of the apically located cellular cementum, some cementoblasts become embedded in the cementoid matrix and become cementocytes. As apparently terminally differentiated cells embedded in a mineralized extracellular matrix, cementocytes are part of a select group of specialized cells, also including osteocytes, hypertrophic chondrocytes, and odontoblasts. The differentiation and potential function(s) of cementocytes are virtually unknown, and the question may be posed whether the cementocyte is a dynamic actor in cementum in comparable fashion with the osteocyte in the skeleton, responding to changing tooth functions and endocrine signals and actively directing local cementum metabolism. This review summarizes the literature with regard to cementocytes, comparing them to their closest "cousins," the osteocytes, where insights gained from osteocyte studies serve to inform the critical examination of cementocytes. The review identifies important unanswered questions about these cells regarding their origins, differentiation, morphology and lacuno-canalicular system, selective markers, and potential functions.
- Role of PHOSPHO1 in Periodontal Development and Function. [Journal Article]
- JDJ Dent Res 2016; 95(7):742-51
- The tooth root and periodontal apparatus, including the acellular and cellular cementum, periodontal ligament (PDL), and alveolar bone, are critical for tooth function. Cementum and bone mineralizati…
The tooth root and periodontal apparatus, including the acellular and cellular cementum, periodontal ligament (PDL), and alveolar bone, are critical for tooth function. Cementum and bone mineralization is regulated by factors including enzymes and extracellular matrix proteins that promote or inhibit hydroxyapatite crystal growth. Orphan Phosphatase 1 (Phospho1, PHOSPHO1) is a phosphatase expressed by chondrocytes, osteoblasts, and odontoblasts that functions in skeletal and dentin mineralization by initiating deposition of hydroxyapatite inside membrane-limited matrix vesicles. The role of PHOSPHO1 in periodontal formation remains unknown and we aimed to determine its functional importance in these tissues. We hypothesized that the enzyme would regulate proper mineralization of the periodontal apparatus. Spatiotemporal expression of PHOSPHO1 was mapped during periodontal development, and Phospho1(-/-) mice were analyzed using histology, immunohistochemistry, in situ hybridization, radiography, and micro-computed tomography. The Phospho1 gene and PHOSPHO1 protein were expressed by active alveolar bone osteoblasts and cementoblasts during cellular cementum formation. In Phospho1(-/-) mice, acellular cementum formation and mineralization were unaffected, whereas cellular cementum deposition increased although it displayed delayed mineralization and cementoid. Phospho1(-/-) mice featured disturbances in alveolar bone mineralization, shown by accumulation of unmineralized osteoid matrix and interglobular patterns of protein deposition. Parallel to other skeletal sites, deposition of mineral-regulating protein osteopontin (OPN) was increased in alveolar bone in Phospho1(-/-) mice. In contrast to the skeleton, genetic ablation of Spp1, the gene encoding OPN, did not ameliorate dentoalveolar defects in Phospho1(-/-) mice. Despite alveolar bone mineralization defects, periodontal attachment and function appeared undisturbed in Phospho1(-/-) mice, with normal PDL architecture and no evidence of bone loss over time. This study highlights the role of PHOSPHO1 in mineralization of alveolar bone and cellular cementum, further revealing that acellular cementum formation is not substantially regulated by PHOSPHO1 and likely does not rely on matrix vesicle-mediated initiation of mineralization.
- Rsk2, the Kinase Mutated in Coffin-Lowry Syndrome, Controls Cementum Formation. [Journal Article]
- JDJ Dent Res 2016; 95(7):752-60
- The ribosomal S6 kinase RSK2 is essential for osteoblast function, and inactivating mutations of RSK2 cause osteopenia in humans with Coffin-Lowry syndrome (CLS). Alveolar bone loss and premature too…
The ribosomal S6 kinase RSK2 is essential for osteoblast function, and inactivating mutations of RSK2 cause osteopenia in humans with Coffin-Lowry syndrome (CLS). Alveolar bone loss and premature tooth exfoliation are also consistently reported symptoms in CLS patients; however, the pathophysiologic mechanisms are unclear. Therefore, aiming to identify the functional relevance of Rsk2 for tooth development, we analyzed Rsk2-deficient mice. Here, we show that Rsk2 is a critical regulator of cementoblast function. Immunohistochemistry, histology, micro-computed tomography imaging, quantitative backscattered electron imaging, and in vitro assays revealed that Rsk2 is activated in cementoblasts and is necessary for proper acellular cementum formation. Cementum hypoplasia that is observed in Rsk2-deficient mice causes detachment and disorganization of the periodontal ligament and was associated with significant alveolar bone loss with age. Moreover, Rsk2-deficient mice display hypomineralization of cellular cementum with accumulation of nonmineralized cementoid. In agreement, treatment of the cementoblast cell line OCCM-30 with a Rsk inhibitor reduces formation of mineralization nodules and decreases the expression of cementum markers. Western blot analyses based on antibodies against Rsk1, Rsk2, and an activated form of the 2 kinases confirmed that Rsk2 is expressed and activated in differentiating OCCM-30 cells. To discriminate between periodontal bone loss and systemic bone loss, we additionally crossed Rsk2-deficient mice with transgenic mice overexpressing the osteoanabolic transcription factor Fra1. Fra1 overexpression clearly increases systemic bone volume in Rsk2-deficient mice but does not protect from alveolar bone loss. Our results indicate that cell autonomous cementum defects are causing early tooth loss in CLS patients. Moreover, we identify Rsk2 as a nonredundant regulator of cementum homeostasis, alveolar bone maintenance, and periodontal health, with all these features being independent of Rsk2 function in systemic bone formation.
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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. [Review]
- JPJ Periodontal Res 2016; 51(6):699-715
- 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 mediator…
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.