The temporomandibular joint (TMJ) is one of the most used joints in the body. Defects and wear in the cartilage of the joint, condyle, and fibrocartilage disc lie at the heart of many common TMJ disorders. During postnatal development, the condyle acts as a growth center for the mandible, with cells moving as a conveyor belt away from the top of the condyle as they differentiate. The superficial layers of the condyle have been proposed to contain stem/progenitor populations to allow growth and maintain homeostasis. Here we have focused on the role of fibroblast-specific protein 1 (FSP1; also known as S100a4) as a key fibroblast stem/progenitor marker for the condyle. Lineage tracing with FSP1-Cre;R26RmTmG mice revealed that FSP1-expressing cells were restricted to the superficial fibroblast zone, giving rise to all layers of the condyle over time. The FSP1-expressing cells overlapped with other putative stem cell markers of the condyle, such as Gli1 and scleraxis. BrdU pulse chase experiments highlighted that a subset of FSP1 fibrocartilage was label retaining, suggesting that FSP1 labels a novel stem/progenitor cell population in the condyle. Destruction of FSP1-expressing cells by conditional diphtheria toxin activity in FSP1-Cre;R26RDTA mice resulted in severe TMJ osteoarthritis with loss of the cartilage structure. Lgr5-expressing cells in the superficial layer of the condyle have been shown to create a Wnt inhibitory niche. FSP1 expression postnatally was associated with a reduction in canonical Wnt activity in the condyle. Importantly, constitutive activation of Wnt/β catenin in FSP1-expressing cells led to a downregulation of FSP1 and progressive postnatal loss of TMJ condylar hyaline cartilage due to loss of the superficial stem/progenitor cells. These data demonstrate a novel role for FSP1-expressing cells in the superficial zone in growth and maintenance of the TMJ condylar cartilage and highlight the importance of regulating Wnt activity in this population.

• Klíčová slova
• Wnt signaling, condyle, fibrocartilage, osteoarthritis, stem cell, temporomandibular disorders,
• MeSH
• fibroblasty metabolismus   MeSH
• homeostáza fyziologie   MeSH
• kmenové buňky * metabolismus   fyziologie   MeSH
• myši transgenní MeSH
• myši MeSH
• processus condylaris mandibulae růst a vývoj   cytologie   metabolismus   MeSH
• receptory spřažené s G-proteiny MeSH
• S100 kalcium vázající protein A4 * metabolismus   fyziologie   MeSH
• temporomandibulární kloub * růst a vývoj   cytologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• Lgr5 protein, mouse MeSH Prohlížeč
• receptory spřažené s G-proteiny MeSH
• S100 kalcium vázající protein A4 * MeSH
• S100a4 protein, mouse MeSH Prohlížeč

Organs throughout the body develop both asymmetrically and symmetrically. Here, we assess how symmetrical teeth in reptiles can be created from asymmetrical tooth germs. Teeth of lepidosaurian reptiles are mostly anchored to the jaw bones by pleurodont ankylosis, where the tooth is held in place on the labial side only. Pleurodont teeth are characterized by significantly asymmetrical development of the labial and lingual sides of the cervical loop, which later leads to uneven deposition of hard tissue. On the other hand, acrodont teeth found in lizards of the Acrodonta clade (i.e. agamas, chameleons) are symmetrically ankylosed to the jaw bone. Here, we have focused on the formation of the symmetrical acrodont dentition of the veiled chameleon (Chamaeleo calyptratus). Intriguingly, our results revealed distinct asymmetries in morphology of the labial and lingual sides of the cervical loop during early developmental stages, both at the gross and ultrastructural level, with specific patterns of cell proliferation and stem cell marker expression. Asymmetrical expression of ST14 was also observed, with a positive domain on the lingual side of the cervical loop overlapping with the SOX2 domain. In contrast, micro-CT analysis of hard tissues revealed that deposition of dentin and enamel was largely symmetrical at the mineralization stage, highlighting the difference between cervical loop morphology during early development and differentiation of odontoblasts throughout later odontogenesis. In conclusion, the early asymmetrical development of the enamel organ seems to be a plesiomorphic character for all squamate reptiles, while symmetrical and precisely orchestrated deposition of hard tissue during tooth formation in acrodont dentitions probably represents a novelty in the Acrodonta clade.

• MeSH
• čelisti fyziologie   MeSH
• ještěři * anatomie a histologie   fyziologie   MeSH
• odontogeneze fyziologie   MeSH
• vývoj kostí fyziologie   MeSH
• zuby fyziologie   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The Eda pathway ( Eda, Edar, Edaradd) plays an important role in tooth development, determining tooth number, crown shape, and enamel formation. Here we show that the Eda pathway also plays a key role in root development. Edar (the receptor) is expressed in Hertwig's epithelial root sheath (HERS) during root development, with mutant mice showing a high incidence of taurodontism: large pulp chambers lacking or showing delayed bifurcation or trifurcation of the roots. The mouse upper second molars in the Eda pathway mutants show the highest incidence of taurodontism, this enhanced susceptibility being matched in human patients with mutations in EDA-A1. These taurodont teeth form due to defects in the direction of extension of the HERS from the crown, associated with a more extensive area of proliferation of the neighboring root mesenchyme. In those teeth where the angle at which the HERS extends from the crown is very wide and therefore more vertical, the mutant HERSs fail to reach toward the center of the tooth in the normal furcation region, and taurodont teeth are created. The phenotype is variable, however, with milder changes in angle and proliferation leading to normal or delayed furcation. This is the first analysis of the role of Eda in the root, showing a direct role for this pathway during postnatal mouse development, and it suggests that changes in proliferation and angle of HERS may underlie taurodontism in a range of syndromes.

• Klíčová slova
• ectodermal dysplasia, ectodysplasins, epithelium, furcation defects, periodontium, tooth,
• MeSH
• abnormality zubů genetika   MeSH
• dítě MeSH
• ektodysplasiny genetika   MeSH
• fenotyp MeSH
• kavita zubní dřeně abnormality   MeSH
• lidé MeSH
• mladiství MeSH
• moláry abnormality   embryologie   MeSH
• myši MeSH
• odontogeneze genetika   MeSH
• rentgenová mikrotomografie MeSH
• signální transdukce MeSH
• zubní kořen abnormality   embryologie   MeSH
• zvířata MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• EDA protein, human MeSH Prohlížeč
• Eda protein, mouse MeSH Prohlížeč
• ektodysplasiny MeSH

c-Fos homozygous mice lack osteoclasts with a failure of the teeth to erupt and with an arrest of root development. Here, we characterize the defects associated with the failure in root development and the loss of the tooth-bone interface, and we investigate the underlying causes. We show that, while homozygous c-Fos mice have no multinucleated osteoclasts, heterozygous mice have a reduction in the number of osteoclasts with a reduction in the tooth-bone interface during development and subtle skeletal defects postnatally. In the homozygous mutants bone is found to penetrate the tooth, particularly at the apical end, physically disrupting the root forming HERS (Hertwig's epithelial root sheath) cells. The cells of the HERS continue to proliferate but cannot extend downward due to the presence of bone, leading to a loss of root formation. Tooth germ culture showed that the developing tooth invaded the static bone in mutant tissue, rather than the bone encroaching on the tooth. Although c-Fos has been shown to be expressed in developing teeth, the defect in maintenance of the tooth-bone interface appears to be driven solely by the lack of osteoclasts, as this defect can be rescued in the presence of donor osteoclasts. The rescue suggests that signals from the tooth recruit osteoclasts to clear the bone from around the tooth, allowing the tooth to grow, form roots, and later erupt.

• Klíčová slova
• HERS, bone, osteopetrosis, remodeling, rescue, tooth,
• MeSH
• abnormality čelisti genetika   patofyziologie   MeSH
• homozygot MeSH
• maxilofaciální vývoj genetika   fyziologie   MeSH
• mutantní kmeny myší MeSH
• myši inbrední C57BL genetika   MeSH
• myši MeSH
• osteoklasty fyziologie   MeSH
• prořezávání zubů genetika   fyziologie   MeSH
• protoonkogenní proteiny c-fos genetika   fyziologie   MeSH
• zubní kořen abnormality   růst a vývoj   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• protoonkogenní proteiny c-fos MeSH

The Myb locus encodes the c-Myb transcription factor involved in controlling a broad variety of cellular processes. Recently, it has been shown that c-Myb may play a specific role in hard tissue formation; however, all of these results were gathered from an analysis of intramembranous ossification. To investigate a possible role of c-Myb in endochondral ossification, we carried out our study on the long bones of mouse limbs during embryonic development. Firstly, the c-myb expression pattern was analyzed by in situ hybridization during endochondral ossification of long bones. c-myb positive areas were found in proliferating as well as hypertrophic zones of the growth plate. At early embryonic stages, localized expression was also observed in the perichondrium and interdigital areas. The c-Myb protein was found in proliferating chondrocytes and in the perichondrium of the forelimb bones (E14.5-E17.5). Furthermore, protein was detected in pre-hypertrophic as well as hypertrophic chondrocytes. Gain-of-function and loss-of-function approaches were used to test the effect of altered c-myb expression on chondrogenesis in micromass cultures established from forelimb buds of mouse embryos. A loss-of-function approach using c-myb specific siRNA decreased nodule formation, as well as downregulated the level of Sox9 expression, a major marker of chondrogenesis. Transient c-myb overexpression markedly increased the formation of cartilage nodules and the production of extracellular matrix as detected by intense staining with Alcian blue. Moreover, the expression of early chondrogenic genes such as Sox9, Col2a1 and activity of a Col2-LUC reporter were increased in the cells overexpressing c-myb while late chondrogenic markers such as Col10a1 and Mmp13 were not significantly changed or were downregulated. Taken together, the results of this study demonstrate that the c-Myb transcription factor is involved in the regulation and promotion of endochondral bone formation.

• Klíčová slova
• Chondrogenesis, Endochondral bone, Micromass cultures, Mouse limbs, Up- and down-regulation, siRNA,
• MeSH
• biologické markery metabolismus   MeSH
• buněčná diferenciace MeSH
• chondrogeneze fyziologie   MeSH
• hybridizace in situ MeSH
• končetiny embryologie   MeSH
• myši MeSH
• protoonkogenní proteiny c-myb genetika   fyziologie   MeSH
• umlčování genů MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• biologické markery MeSH
• protoonkogenní proteiny c-myb MeSH

Caspase-3 and -7 are generally known for their central role in the execution of apoptosis. However, their function is not limited to apoptosis and under specific conditions activation has been linked to proliferation or differentiation of specialised cell types. In the present study, we followed the localisation of the activated form of caspase-7 during intramembranous (alveolar and mandibular bones) and endochondral (long bones of limbs) ossification in mice. In both bone types, the activated form of caspase-7 was detected from the beginning of ossification during embryonic development and persisted postnatally. The bone status was investigated by microCT in both wild-type and caspase-7-deficient adult mice. Intramembranous bone in mutant mice displayed a statistically significant decrease in volume while the mineral density was not altered. Conversely, endochondral bone showed constant volume but a significant decrease in mineral density in caspase-7 knock-out mice. Cleaved caspase-7 was present in a number of cells that did not show signs of apoptosis. PCR array analysis of the mandibular bone of caspase-7-deficient versus wild-type mice pointed to a significant decrease in mRNA levels for Msx1 and Smad1 in early bone formation. These observations might explain the decrease in the alveolar bone volume of adult knock-out mice. In conclusion, this study is the first to report a non-apoptotic function of caspase-7 in osteogenesis and also demonstrates further specificities in endochondral versus intramembranous ossification.

• MeSH
• apoptóza MeSH
• embryonální vývoj MeSH
• kaspasa 3 metabolismus   MeSH
• kaspasa 7 genetika   metabolismus   MeSH
• kosti a kostní tkáň diagnostické zobrazování   metabolismus   patologie   MeSH
• myši knockoutované MeSH
• myši MeSH
• osteogeneze * MeSH
• osteokalcin metabolismus   MeSH
• počítačová rentgenová tomografie MeSH
• protein Smad1 genetika   metabolismus   MeSH
• transkripční faktor MSX1 genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• kaspasa 3 MeSH
• kaspasa 7 MeSH
• Msx1 protein, mouse MeSH Prohlížeč
• osteokalcin MeSH
• protein Smad1 MeSH
• transkripční faktor MSX1 MeSH

OBJECTIVES: The primary enamel knot (PEK) is a population of cells that shows spatio-temporal restricted apoptosis during tooth development. It has been shown that caspase-9 and Apaf-1 are essential for apoptosis in the PEK as well as the central caspase-3. Caspase-7, as another executioner member in the caspase machinery, is considered to have caspase-3 like properties. DESIGN: The aim of this study was to detect caspase-7 activation during molar tooth development with a special focus on the cells of the PEK and to correlate the expression with the pattern of apoptosis and caspase-3 activation. Apoptosis in the PEK was investigated in caspase-7 deficient mice to examine the functional consequence of loss of this specific caspase. In addition, odontoblasts and ameloblasts, which are known to undergo cell death during their secretory and maturation stages, were investigated. RESULTS: Cleaved caspase-7 was found in the apoptotic region of the PEK, however, caspase-7-deficient mice still possessed apoptotic cells in the PEK in a similar distribution to the wild type. Caspase-7 is therefore not essential for apoptosis in the PEK. Notably, cleaved caspase-7-positive cells were found at later stages in odontoblasts and ameloblasts, but expression did not correlate with apoptosis in these tissues. CONCLUSIONS: The results indicate a non-essential apoptotic role of caspase-7 in the PEK apoptosis but suggest also possible non-apoptotic functions for caspase-7 in tooth development.

• MeSH
• ameloblasty cytologie   MeSH
• apoptóza fyziologie   MeSH
• kaspasa 7 nedostatek   genetika   metabolismus   MeSH
• koncové značení zlomů DNA in situ MeSH
• moláry metabolismus   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• odontoblasty cytologie   MeSH
• odontogeneze genetika   fyziologie   MeSH
• počítačová rentgenová tomografie MeSH
• vývojová regulace genové exprese MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• kaspasa 7 MeSH

Functional tooth germs in mammals, reptiles, and chondrichthyans are initiated from a dental lamina. The longevity of the lamina plays a role in governing the number of tooth generations. Monophyodont species have no replacement dental lamina, while polyphyodont species have a permanent continuous lamina. In diphyodont species, the dental lamina fragments and regresses after initiation of the second tooth generation. Regression of the lamina seems to be an important mechanism in preventing the further development of replacement teeth. Defects in the complete removal of the lamina lead to cyst formation and has been linked to ameloblastomas. Here, we show the previously unknown mechanisms behind the disappearance of the dental lamina, involving a combination of cell migration, cell-fate transformation, and apoptosis. Lamina regression starts with the loss of the basement membrane, allowing the epithelial cells to break away from the lamina and migrate into the surrounding mesenchyme. Cells deactivate epithelial markers (E-cadherin, cytokeratin), up-regulate Slug and MMP2, and activate mesenchymal markers (vimentin), while residual lamina cells are removed by apoptosis. The uncovering of the processes behind lamina degradation allows us to clarify the evolution of diphyodonty, and provides a mechanism for future manipulation of the number of tooth generations.

• MeSH
• apoptóza MeSH
• dentice trvalá * MeSH
• epitelo-mezenchymální tranzice MeSH
• epitelové buňky cytologie   MeSH
• kadheriny metabolismus   MeSH
• keratiny metabolismus   MeSH
• matrixová metaloproteinasa 2 metabolismus   MeSH
• miniaturní prasata MeSH
• odontogeneze fyziologie   MeSH
• pohyb buněk MeSH
• prasata MeSH
• protoonkogenní proteiny c-myb metabolismus   MeSH
• rodina transkripčních faktorů Snail MeSH
• transkripční faktory metabolismus   MeSH
• vimentin metabolismus   MeSH
• zubní zárodek cytologie   embryologie   MeSH
• zuby mléčné * MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• kadheriny MeSH
• keratiny MeSH
• matrixová metaloproteinasa 2 MeSH
• protoonkogenní proteiny c-myb MeSH
• rodina transkripčních faktorů Snail MeSH
• transkripční faktory MeSH
• vimentin MeSH

Laser capture microdissection (LCM) uniquely allows the selection of specific cell populations from histological sections. These selected cells are then catapulted into a test tube without any contamination from surrounding tissues. During the last ten years, many significant results have been achieved, particularly at the level of DNA and RNA where amplification techniques are available. However, where amplification procedures are difficult, the benefits of LCM diminish. To overcome such difficulties, a novel approach, combining laser capture microdissection and flow cytometry, has been tested here for detection of apoptosis and proliferation in tissue bound cell populations without any amplification steps. The mouse cap stage molar tooth germ was used as a model. At the centre of the inner enamel epithelium, the primary enamel knot is a clearly defined apoptotic population with minimal proliferation, flanked by the highly proliferative cervical loops on each side. Thus within the tooth germ epithelium at this stage, two distinct populations of cells are found side by side. These populations were selected by laser capture microdissection and then analysed by flow cytometry for apoptosis and proliferation. Flow cytometric results correlated well with immunohistochemical findings, demonstrating the success and sensitivity of this combined procedure.

• MeSH
• apoptóza fyziologie   MeSH
• epitelové buňky cytologie   MeSH
• gestační stáří MeSH
• imunohistochemie MeSH
• koncové značení zlomů DNA in situ MeSH
• kryoprezervace MeSH
• laserová terapie metody   MeSH
• mikrodisekce metody   MeSH
• moláry embryologie   MeSH
• myši MeSH
• orgán skloviny cytologie   MeSH
• počet buněk MeSH
• proliferace buněk MeSH
• proliferační antigen buněčného jádra analýza   MeSH
• průtoková cytometrie * MeSH
• senzitivita a specificita MeSH
• zubní krček cytologie   embryologie   MeSH
• zubní zárodek cytologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• proliferační antigen buněčného jádra MeSH

Tooth agenesis may originate from either genetic or environmental factors. Genetically determined hypodontic disorders appear as isolated features or as part of a syndrome. Msx1, Pax9, and Axin2 are involved in non-syndromic hypodontia, while genes such as Shh, Pitx2, Irf6, and p63 are considered to participate in syndromic genetic disorders, which include tooth agenesis. In dentistry, artificial tooth implants represent a common solution to tooth loss problems; however, molecular dentistry offers promising solutions for the future. In this paper, the genetic and molecular bases of non-syndromic and syndromic hypodontia are reviewed, and the advantages and disadvantages of tissue engineering in the clinical treatment of tooth agenesis are discussed.

• MeSH
• abnormality úst komplikace   genetika   MeSH
• anodoncie komplikace   genetika   terapie   MeSH
• lidé MeSH
• odontogeneze genetika   MeSH
• předpověď MeSH
• syndrom MeSH
• tkáňové inženýrství trendy   MeSH
• zubní lékařství trendy   MeSH
• zubní zárodek fyziologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH