A5018373846- Hedgehog Signaling Pathway Studies
- Oral and Maxillofacial Pathology
- Pluripotent Stem Cells Research
- Tumors and Oncological Cases
- Salivary Gland Disorders and Functions
- dental development and anomalies
- Macrophage Migration Inhibitory Factor
- Mesenchymal stem cell research
- Bone Metabolism and Diseases
- Renal and related cancers
- Wnt/β-catenin signaling in development and cancer
- Connective tissue disorders research
- Developmental Biology and Gene Regulation
- Cancer-related molecular mechanisms research
- Genetic and Kidney Cyst Diseases
- Genetic and rare skin diseases.
- Cancer and Skin Lesions
- RNA Research and Splicing
- Cancer-related gene regulation
- Fibroblast Growth Factor Research
- Tissue Engineering and Regenerative Medicine
- Single-cell and spatial transcriptomics
- Bone and Dental Protein Studies
- Dietary Effects on Health
- Congenital heart defects research
Tokyo Dental College
2016-2025
The University of Tokyo
2017-2020
Hokkaido University
1996-2010
The transcriptional regulator Runx2 (runt-related transcription factor 2) has essential but distinct roles in osteoblasts and chondrocytes skeletal development. However, Runx2-mediated regulatory mechanisms underlying the distinctive programming of are not well understood. Here, we perform an integrative analysis to investigate Runx2-DNA binding chromatin accessibility ex vivo using neonatal chondrocytes. We find that engages with cell-type-distinct chromatin-accessible regions, potentially...
Exposure to foreign particles sometimes causes inflammatory reactions through production of cytokines and chemoattractants by phagocytic cells. In this study, we focused on macrophage migration inhibitory factor (MIF) evaluate its pathophysiological role in the process. Immunohistochemical analysis human pseudosynovial tissues retrieved at revision total hip arthroplasty showed that infiltrating mononuclear multinuclear cells were positively stained both an anti‐CD68 antibody anti‐human MIF...
Background We have previously reported that repeated treatment of human periodontal ligament cells and murine pre-osteoblast MC3T3-E1 with transforming growth factor-beta 1 (TGF-β1) inhibited their osteoblastic differentiation because decreased insulin-like factor-1 (IGF-1) secretion. also found IGF-1/PI3K signaling plays an important role in osteoblast induced by TGF-β1 treatment; however, the downstream controlling this remains unknown. The aim current study is to investigate whether Akt...
We recently reported a new method to purify the induced pluripotent stem (iPS)-derived osteoprogenitors (iPSop). In this paper, we optimized procedure and characterized cells at each process step. observed that 10 days of treatment with FGF-2, IGF-1 TGF-β (FIT) resulted in early-phase osteoblasts 14 late-phase osteoblasts. found 1,25(OH)2 vitamin D3 increased expression osteocalcin decreased tissue-non-specific alkaline phosphatase runt-related transcription factor 2 (RUNX2) iPSop-day14...
Although the skeleton is essential for locomotion, endocrine functions, and hematopoiesis, molecular mechanisms of human skeletal development remain to be elucidated. Here, we introduce an integrative method model by combining in vitro sclerotome induction from pluripotent stem cells vivo endochondral bone formation implanting beneath renal capsules immunodeficient mice. Histological scRNA-seq analyses reveal that induced bones recapitulate ossification are composed mouse circulatory cells....
Abstract Objectives/Aims: The requisite conditions for successful bone tissue engineering are efficient stem cell differentiation into osteogenic cells and a suitable scaffold. In this study, we investigated in vivo regeneration from transplanted induced pluripotent (iPSCs). Materials Methods: Two critical-sized calvarial defects were created 36 rats. surgical sites randomly assigned to one of three treatments test the healing effectiveness scaffold alone, with iPSCs or salt solution as...
Runx2 is a master regulator of bone formation, and its dysfunction causes cleidocranial dysplasia (CCD) in humans. When iPS cells were generated from patients with CCD Runx2-deficient using gene-editing techniques, abnormal laminopathy-like nuclei observed. showed reduced Lamin A/C expression, but not protein levels. However, cells, both the gene expression levels Nesprin1 reduced, perinuclear actin fibers sparser, nuclear stiffness was reduced. Forced increased did improve morphology. In...
In this study, we developed a new method to stimulate osteogenic differentiation in tissue-nonspecific alkaline phosphatase (TNAP)-positive cells liberated from human induced pluripotent stem (hiPSCs)-derived embryoid bodies (EBs) with 14 days long TGF-β/IGF-1/FGF-2 treatment. TNAP is marker protein of osteolineage cells. We analyzed and isolated TNAP-positive E-cadherin-negative nonepithelial by fluorescence-activated cell sorting. Treating the combination transforming growth factor...
Bone resorption and formation are dynamic processes that occur in both normal injured bone tissues. Regulation of these is mediated at the local level by cytokines growth factors. Macrophage migration inhibitory factor (MIF) one proinflammatory activates macrophages regulates production other cytokines, such as tumour necrosis factor‐α interleukin‐1. We here demonstrate, reverse transcription–polymerase chain reaction, high expression MIF mRNA murine osteoblasts obtained from mouse neonatal...
Runt-related transcription factor 2 (RUNX2) haploinsufficiency causes cleidocranial dysplasia (CCD) which is characterized by supernumerary teeth, short stature, clavicular dysplasia, and osteoporosis. At present, as a therapeutic strategy for osteoporosis, mesenchymal stem cell (MSC) transplantation therapy performed in addition to drug therapy. However, MSC-based osteoporosis CCD patients difficult due reduction the ability of MSCs differentiate into osteoblasts resulting from impaired...
Gorlin syndrome is a genetic disorder of autosomal dominant inheritance that predisposes the affected individual to variety disorders are attributed largely heterozygous germline patched1 (PTCH1) mutations. PTCH1 hedgehog (Hh) receptor as well repressor, mutation which leads constitutive activation Hh pathway. pathway encompasses wide cellular signaling cascades, involve several molecules; however, no associated genotype-phenotype correlations have been reported. Recently, mutations in...
Two genetic diseases, Gorlin syndrome and McCune-Albright (MAS), show completely opposite symptoms in terms of bone mineral density hedgehog (Hh) activity. In this study, we utilized human induced pluripotent stem cell (iPSC)-based models the two diseases to understand roles Hh signaling osteogenesis. syndrome-derived iPSCs showed increased osteoblastogenesis mineralization with activation upregulation a set transcription factors an osteogenic culture, compared isogenic control. MAS-specific...
Clinically relevant human induced pluripotent stem cell (hiPSC) derivatives require efficient protocols to differentiate hiPSCs into specific lineages. Here we developed a fully defined xeno-free strategy direct toward osteoblasts within 21 days. The successfully achieved the osteogenic induction of four independently derived hiPSC lines by sequential use combinations small-molecule inducers. first generated mesodermal cells, which subsequently recapitulated developmental expression pattern...
Stem cell-based regeneration therapy offers new therapeutic options for patients with bone defects because of significant advances in stem cell research. Although marrow mesenchymal cells are the ideal material using cell, they difficult to obtain. Induced pluripotent (iPSCs) now considered an attractive tool tissue engineering. Recently, efficiency establishing iPSCs has been improved by use Sendai virus vector, and it become easier establish from several type somatic cells. In our previous...
Gorlin syndrome is an autosomal dominant inherited that predisposes a patient to the formation of basal cell carcinomas, odontogenic keratocysts, and skeletal anomalies. Causative mutations in several genes associated with sonic hedgehog (SHH) signaling pathway, including PTCH1, have been identified patients. However, no definitive genotype-phenotype correlations are evident these patients, their clinical presentation varies greatly, often leading delayed diagnosis treatment. We generated...
Previous studies have shown that neutralization of macrophage migration inhibitory factor (MIF) by anti-MIF antibody reduces intestinal inflammation in mice. In this study we tested whether or not autoantibody induced DNA vaccine targeting MIF protects mice against experimental colitis. Mice were administered a MIF-deoxyribonucleic acid (DNA) introducing oligonucleotides encoding helper T epitope into the cDNA sequence murine vivo electroporation. Preventive effects method dextran sulphate...
A missense mutation of the guanine nucleotide binding protein alpha stimulating activity polypeptide 1 ( GNAS) gene, typically Arg201Cys or Arg201His (R201H/R201C), leads to constitutive activation Gsα-cyclic AMP (cAMP) signaling pathway that causes several diseases. However, no germline mutations GNAS have been identified date, likely due their lethality, and robust human cell models generated. Therefore, aim this study was generate GNAS-mutated disease-specific induced pluripotent stem...
Fibroblast growth factor 8 (FGF8) is known to be a potent stimulator of canonical Wnt/β-catenin activity, an essential for tooth development. In this study, we analyzed the effects co-administration FGF8 and CHIR99021 (GSK3β inhibitor) on differentiation dental mesenchymal cells into odontoblasts. Utilizing Cre-mediated EGFP reporter mice, dentin matrix protein 1 (Dmp1) expression was examined in mouse neonatal molar germs. At birth, Dmp1-EGFP not found but rather epithelial cells, after...