記述言語：英語   出版者・発行元：Journal of Cellular Physiology  

Enhanced osteoclastogenesis causes bone fragility, osteoporosis, and an increased risk of fractures. Recent studies have suggested a possible correlation between osteoporosis and the pathological features of Parkinson's disease (PD). To establish a molecular link between these conditions, we focused on the physiological function of the PD-related protein ubiquitin carboxy-terminal hydrolase L1 (UCHL1) in bone remodeling. To this end, we investigated the role of UCHL1 in regulating osteoclast differentiation in Uchl1 spontaneous mutant gad mice. We found that gad-mouse-derived osteoclast progenitors exhibit enhanced osteoclast differentiation. Likewise, CRISPR-mediated Uchl1 knockout in mouse macrophage-derived preosteoclast RAW-D cells increased RANKL-dependent osteoclastogenesis. Supporting this observation, these Uchl1-depleted cells showed elevated expression of osteoclast marker genes. To uncover the molecular mechanisms by which the loss of Uchl1 enhances osteoclast differentiation, we screened for UCHL1-interacting proteins in RAW-D preosteoclast cells and identified AKT1 as a potential UCHL1-regulated protein. UCHL1 depletion in preosteoclasts led to increased Thr308/Ser473 phosphorylation of AKT1. Furthermore, ectopic expression of UCHL1 decreased the K63-linked polyubiquitination of AKT1. These findings suggest that UCHL1 is critical in partially suppressing osteoclastogenesis through modulating AKT signaling.

DOI： 10.1002/jcp.70032

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出版者・発行元：Pediatric Dental Journal  

Purpose: This study was conducted to explore the possibility of detecting the presence of impacted teeth in the upper midline using facial morphometric measurements. Materials and Methods: The study included 260 children, aged 2–13 years, who visited our university hospital. To measure facial morphology, facial photographs were taken along with a ruler, and the correlation between each facial measurement point and the presence of mesiodens was statistically analyzed. Results: Each measurement point increased in a time-dependent manner and there was a correlation between age and distance. In contrast, the ratio of the inner-canthal distance to the outer-canthal distance was not associated with age. Moreover, an increase in this ratio suggested the possible presence of mesiodens. Since age is associated with the presence of mesiodens within the inner canthal distance, a multivariate analysis that considered the effects of age and sex was performed and showed that the inner canthus/outer canthus ratio was 0.45. When the odds ratio of the presence of mesiodens in the group of less than 1.0 was set to 1.0, the odds ratio of the group of 0.45 or more was 5.36. Conclusion: The presence of mesiodens can be predicted by measuring the ratio of the inner canthal distance to the outer canthal distance.

DOI： 10.1016/j.pdj.2023.04.001

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記述言語：英語   出版者・発行元：FASEB Journal  

Enamel is formed by the repetitive secretion of a tooth-specific extracellular matrix and its decomposition. Calcification of the enamel matrix via hydroxyapatite (HAP) maturation requires pH cycling to be tightly regulated through the neutralization of protons released during HAP synthesis. We found that Gpr115, which responds to changes in extracellular pH, plays an important role in enamel formation. Gpr115-deficient mice show partial enamel hypomineralization, suggesting that other pH-responsive molecules may be involved. In this study, we focused on the role of Gpr111/Adgrf2, a duplicate gene of Gpr115, in tooth development. Gpr111 was highly expressed in mature ameloblasts. Gpr111-KO mice showed enamel hypomineralization. Dysplasia of enamel rods and high carbon content seen in Gpr111-deficient mice suggested the presence of residual enamel matrices in enamel. Depletion of Gpr111 in dental epithelial cells induced the expression of ameloblast-specific protease, kallikrein-related peptidase 4 (Klk4), suggesting that Gpr111 may act as a suppressor of Klk4 expression. Moreover, reduction of extracellular pH to 6.8 suppressed the expression of Gpr111, while the converse increased Klk4 expression. Such induction of Klk4 was synergistically enhanced by Gpr111 knockdown, suggesting that proper enamel mineralization may be linked to the modulation of Klk4 expression by Gpr111. Furthermore, our in vitro suppression of Gpr111 and Gpr115 expression indicated that their suppressive effect on calcification was additive. These results suggest that both Gpr111 and Gpr115 respond to extracellular pH, contribute to the expression of proteolytic enzymes, and regulate the pH cycle, thereby playing important roles in enamel formation.

DOI： 10.1096/fj.202202053R

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記述言語：英語   出版者・発行元：Journal of Oral Biosciences  

Objectives: Epithelial-mesenchymal interactions are extremely important in tooth development and essential for ameloblast differentiation, especially during tooth formation. We aimed to identify the type of mesenchymal cells important in ameloblast differentiation. Methods: We used two types of cell culture systems with chambers and found that a subset of debtal mesenchimal cells is important for the differentiatiuon of dental spithelial cells into ameloblasts. Further, we induced dental pulp stem cell-like cells from dental pulp stem cells using the small molecule compound BIO ( a GSK-3 inhibitor IX) to clarify the mechanism involved in ameloblast differentiation induced by dental pulp stem cells. Results: The BIO-induced dental pulp cells promoted the expression of mesenchymal stem cell markers Oct3/4 and Bcrp1. Furthermore, we used artificial dental pulp stem cells induced by BIO to identify the molecules expressed in dental pulp stem cells required for ameloblast differentiation. Panx3 expression was induced in the dental pulp stem cell through interaction with the dental epithelial cells. In addition, ATP release from cells increased in Panx3-expressing cells. We also confirmed that ATP stimulation is accepted in dental epithelial cells. Conclusions: These results showed that the Panx3 expressed in dental pulp stem cells is important for ameloblast differentiation and that ATP release by Panx3 may play a role in epithelial–mesenchymal interaction.

DOI： 10.1016/j.job.2022.10.002

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記述言語：英語   出版者・発行元：(一社)歯科基礎医学会  

チャンバー内細胞培養系を用いて歯原性間葉系細胞のサブセットが歯原性上皮細胞からエナメル芽細胞への分化に重要であることを発見した。歯髄細胞からGSK3β阻害剤BIOを用いて歯髄幹細胞様細胞を誘導し、歯髄幹細胞により誘導されるエナメル芽細胞分化のメカニズムについて検討した。BIOで誘導された歯髄細胞は間葉系幹細胞マーカーOct3/4およびBcrp1を高発現した。BIOで誘導された人工歯髄幹細胞を用いて、歯髄幹細胞に発現するエナメル芽細胞分化に必要な分子を同定した。歯原性上皮細胞との相互作用を介して歯髄幹細胞でPanx3発現が誘導された。さらにPanx3発現細胞でATP遊離が増加した。ATP刺激は歯原性上皮細胞に受容された。以上の結果から、歯髄幹細胞に発現するPanx3がエナメル芽細胞分化に重要で、Panx3によるATP遊離が上皮間葉系相互作用に寄与すると考えられた。

記述言語：日本語  

記述言語：英語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語