Impaired breakdown of Herwig's epithelial root sheath disturbs tooth root development.

Background: Wnt/β-catenin signaling plays a variety of roles in both the dental epithelium and mesenchyme at most stages of tooth development. In this study, we verified the roles of Hertwig's epithelial root sheath (HERS) breakdown in tooth root development. This breakdown results in formation of epithelial cell rests of Malassez (ERM).

Cell dynamics in Hertwig's epithelial root sheath are regulated by β-catenin activity during tooth root development.

β-catenin, a key mediator of Wnt signaling, plays multiple roles in tooth development. However, the role of β-catenin in Hertwig's epithelial root sheath (HERS) during root formation remains unclear. In this study, we generated inducible tissue-specific β-catenin conditional knockout mice (Ctnnb1 ) to investigate how β-catenin in HERS affects tooth root development.

Antagonistic interactions between osterix and pyrophosphate during cementum formation.

During cementum formation, the key roles of osterix (Osx) and inorganic pyrophosphate (PPi), mainly controlled by nucleotide pyrophosphatase 1 (Npp1; encoded by the Enpp1 gene) and progressive ankylosis protein (Ank), have been demonstrated by animal models displaying altered cementum formation. In this study, we analyzed the relationship of Osx and local PPi during cementum formation using compound mutant mice with their wildtype and corresponding single gene mutants. Importantly, functional defects in PPi regulation led to the induction of Osx expression at the cervical cementum as demonstrated by Enpp1 mutant mice and cementoblasts with the retroviral transduction of small hairpin RNA for Enpp1 or Ank.

Expression of the Hutchinson-Gilford Progeria Mutation Leads to Aberrant Dentin Formation.

Hutchinson-Gilford progeria syndrome (HGPS) is a rare accelerated senescence disease, manifesting dental abnormalities and several symptoms suggestive of premature aging. Although irregular secondary dentin formation in HGPS patients has been reported, pathological mechanisms underlying aberrant dentin formation remain undefined. In this study, we analyzed the mandibular molars of a tissue-specific mouse model that overexpresses the most common HGPS mutation (LMNA, c.

A Reciprocal Interaction between β-Catenin and Osterix in Cementogenesis.

Although accumulating evidence indicates that both β-catenin and osterix (Osx) are essential for bone and tooth development, few studies have investigated the interaction of these two key proteins in the context of cementogenesis. In this study, we used transgenic mice with constitutively active β-catenin and inactive Osx in the dental mesenchyme to address this question. We found that cementoblasts with constitutively active β-catenin require Osx to produce excessive cellular cementum, and that ablation of Osx prevents this abnormal accumulation.

Recessive Mutations in ACPT, Encoding Testicular Acid Phosphatase, Cause Hypoplastic Amelogenesis Imperfecta.

Amelogenesis imperfecta (AI) is a heterogeneous group of genetic disorders affecting tooth enamel. The affected enamel can be hypoplastic and/or hypomineralized. In this study, we identified ACPT (testicular acid phosphatase) biallelic mutations causing non-syndromic, generalized hypoplastic autosomal-recessive amelogenesis imperfecta (AI) in individuals from six apparently unrelated Turkish families.

TGF-β Signaling Regulates Cementum Formation through Osterix Expression.

TGF-β/BMPs have widely recognized roles in mammalian development, including in bone and tooth formation. To define the functional relevance of the autonomous requirement for TGF-β signaling in mouse tooth development, we analyzed osteocalcin-Cre mediated Tgfbr2 (OC(Cre)Tgfbr2(fl/fl)) conditional knockout mice, which lacks functional TGF-β receptor II (TβRII) in differentiating cementoblasts and cementocytes. Strikingly, OC(Cre)Tgfbr2(fl/fl) mutant mice exhibited a sharp reduction in cellular cementum mass with reduced matrix secretion and mineral apposition rates.

Testicular acid phosphatase induces odontoblast differentiation and mineralization.

Odontoblasts differentiate from dental mesenchyme during dentin formation and mineralization. However, the molecular mechanisms controlling odontoblast differentiation remain poorly understood. Here, we show that expression of testicular acid phosphatase (ACPT) is restricted in the early stage of odontoblast differentiation in proliferating dental mesenchymal cells and secretory odontoblasts.

Nfic regulates tooth root patterning and growth.

Molecular interactions between epithelium and mesenchyme are important for root formation. Nuclear factor I-C (Nfic) has been identified as a key regulator of root formation. However, the mechanisms of root formation and their interactions between Hertwig's epithelial root sheath (HERS) and mesenchyme remain unclear.

Temporo-spatial requirement of Smad4 in dentin formation.

The TGF-β/BMP family plays an important role in multiple stages of tooth development. TGF-β/BMP signaling is required for odontoblast differentiation and dentin formation; however, the precise molecular mechanisms underlying dentin formation remain unclear. To address the role of TGF-β/BMP signaling in dentin formation, we analyzed mice in which Smad4, a key intracellular mediator of TGF-β/BMP signaling, was subjected to tissue-specific ablation under the control of Dspp, OC, or Col1a1 promoters.

New population of odontoblasts responsible for tooth root formation.

Root formation is initiated with the extension of Hertwig's epithelial root sheath (HERS) after crown morphogenesis. To date, little is known about the molecular and cellular mechanisms controlling root formation. Recently we found rootless molars are formed in the dental mesenchyme-specific β-catenin conditional knockout mice.

Col1a1-cre mediated activation of β-catenin leads to aberrant dento-alveolar complex formation.

Wnt/β-catenin signaling plays a critical role in bone formation and regeneration. Dentin and cementum share many similarities with bone in their biochemical compositions and biomechanical properties. Whether Wnt/β-catenin signaling is involved in the dento-alveolar complex formation is unknown.

Constitutive stabilization of ß-catenin in the dental mesenchyme leads to excessive dentin and cementum formation.

Wnt/ß-catenin signaling plays an important role in morphogenesis and cellular differentiation during development. Essential roles of Wnt/ß-catenin signaling in tooth morphogenesis have been well known, but the involvement of Wnt/ß-catenin signaling in the dental hard tissue formation remains undefined. To understand roles of Wnt/ß-catenin signaling in dentin and cementum formation, we generated and analyzed the conditional ß-catenin stabilized mice in the dental mesenchyme.

Temporospatial localization of acetylcholinesterase activity in the dental epithelium during mouse tooth development.

Acetylcholinesterase (AChE), a principal modulator of cholinergic neurotransmission, also has been demonstrated to be involved in the morphogenetic processes of neuronal and non-neuronal tissues. This study shows that AChE exhibits temporospatial activity in the dental epithelium of the developing mouse tooth. To identify the AChE activity in the mouse tooth during development, we performed enzyme histochemistry on the mouse embryos from embryonic day 13 (E13) to E18 and on the incisors and molars of the neonatal mouse at 10 days after birth (P10).