Publications by authors named "Toshihide Mizoguchi"

α-Smooth muscle actin (α-SMA) is an actin isoform commonly found within vascular smooth muscle cells. Moreover, α-SMA-positive cells are localized in the dental follicle (DF). DF is derived from alveolar bone (AB), cementum, and periodontal ligament (PDL).

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Developing long bones alter their shape while maintaining uniform cortical thickness via coordinated activity of bone-forming osteoblasts and bone-resorbing osteoclasts at periosteal and endosteal surfaces, a process we designate trans-pairing. Two types of trans-pairing shift cortical bone in opposite orientations: peri-forming trans-pairing (peri-t-p) increases bone marrow space and endo-forming trans-pairing (endo-t-p) decreases it, via paired activity of bone resorption and formation across the cortex. Here, we focused on endo-t-p in growing bones.

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Article Synopsis
  • Fibrocartilaginous entheses are structures that include tendons and both mineralized and unmineralized fibrocartilage, all with varying stiffness properties, playing a crucial role in tissue mechanics.
  • The study focused on sclerostin, a protein expressed in fibrochondrocytes, revealing that its levels impact the mineralization processes and overall tissue integrity.
  • Mice lacking the gene for sclerostin showed increased density in fibrocartilaginous regions and enhanced stiffness, indicating that sclerostin is important for maintaining the mechanical properties of these tissues under varying load conditions.
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Objectives: Factors that induce bone formation during orthodontic tooth movement (OTM) remain unclear. Gli1 was recently identified as a stem cell marker in the periodontal ligament (PDL). Therefore, we evaluated the mechanism of differentiation of Cre/LoxP-mediated Gli1/Tomato cells into osteoblasts during OTM.

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Bone tissue provides structural support for our bodies, with the inner bone marrow (BM) acting as a hematopoietic organ. Within the BM tissue, two types of stem cells play crucial roles: mesenchymal stem cells (MSCs) (or skeletal stem cells) and hematopoietic stem cells (HSCs). These stem cells are intricately connected, where BM-MSCs give rise to bone-forming osteoblasts and serve as essential components in the BM microenvironment for sustaining HSCs.

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Objective: Leptin receptor-positive (LepR) periodontal ligament (PDL) cells play a crucial role in osteogenesis during tooth socket healing and orthodontic tooth movement; however, the factors regulating osteoblast differentiation remain unclear. This study aimed to demonstrate the function of low-density lipoprotein receptor-related protein 1 (LRP1) in alveolar bone formation by examining conditional knockout (cKO) mice lacking LRP1 in LepR cells.

Design: Bone mass and formation were examined via bone morphometric analysis.

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  • Tendons connect muscles to bones and are less capable of regenerating compared to muscles, with limited research on tendon regeneration.
  • Sox9, a transcription factor important for cartilage formation, is critical in the early stages of tendon development, but its role in tendon healing after injury is not well understood.
  • In a mouse model of Achilles tendon injury, Sox9 was found to be expressed during the healing process, suggesting it plays a significant role in restoring tendon function and may be linked to stem cells that begin expressing Sox9 post-injury.
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During the process of socket healing after tooth extraction, osteoblasts appear in the tooth socket and form alveolar bone; however, the source of these osteoblasts is still uncertain. Recently, it has been demonstrated that cells expressing Gli1, a downstream factor of sonic hedgehog signaling, exhibit stem cell properties in the periodontal ligament (PDL). Therefore, in the present study, the differentiation ability of Gli1-PDL cells after tooth extraction was analyzed using Gli1-Cre/ROSA26-loxP-stop-loxP-tdTomato (iGli1/Tomato) mice.

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Introduction: The conditional manipulation of genes using the Cre recombinase-locus of crossover in P1 (Cre/loxP) system is an important tool for revealing gene functions and cell lineages in vivo. The outcome of this method is dependent on the performance of Cre-driver mouse strains. In most cases, Cre knock-in mice show better specificity than randomly inserted Cre transgenic mice.

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The lineage of periodontal ligament (PDL) stem cells contributes to alveolar bone (AB) and cementum formation, which are essential for tooth-jawbone attachment. Leptin receptor (LepR), a skeletal stem cell marker, is expressed in PDL; however, the stem cell capacity of LepR PDL cells remains unclear. We used a Cre/LoxP-based approach and detected LepR-cre-labeled cells in the perivascular around the root apex; their number increased with age.

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According to the "hydrodynamic theory," dentinal pain or sensitivity is caused by dentinal fluid movement following the application of various stimuli to the dentin surface. Recent convergent evidence has shown that plasma membrane deformation, mimicking dentinal fluid movement, activates mechanosensitive transient receptor potential (TRP)/Piezo channels in odontoblasts, with the Ca signal eliciting the release of ATP from pannexin-1 (PANX-1). The released ATP activates the P2X receptor, which generates and propagates action potentials in the intradental Aδ afferent neurons.

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Orthodontic tooth movement (OTM) induces bone formation on the alveolar bone of the tension side; however, the mechanism of osteoblast differentiation is not fully understood. Gli1 is an essential transcription factor for hedgehog signaling and functions in undifferentiated cells during embryogenesis. In this study, we examined the differentiation of Gli1 cells in the periodontal ligament (PDL) during OTM using a lineage-tracing analysis.

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Transient receptor potential melastatin-subfamily member 7 (TRPM7) is a bifunctional protein containing a kinase fused to an ion channel permeated with cations, including Ca and Mg. Trpm7-null mice show embryonic lethality. Paired related homeobox 1 (Prx1) is expressed in undifferentiated mesenchymal cells such as the progenitor cells of both chondrocytes and osteoblasts involved in limb skeleton formation.

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Article Synopsis
  • - This study compares the bone healing processes of tooth extraction sockets and femoral fractures in male mice, aiming to uncover the distinct pathological changes during healing.
  • - Using techniques like micro-CT, histology, and RT-PCR, researchers found that tooth sockets heal primarily through intramembranous ossification, while femoral fractures heal via endochondral ossification, showcasing different molecular and cellular mechanisms.
  • - The findings highlight that tooth extraction healing lacks cartilage formation, making it fundamentally different from femoral fracture healing, thus contributing to a deeper understanding of bone regeneration.
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Introduction: The detailed mechanism of the process during bone healing of drill-hole injury has been elucidated, but a crucial factor in regulating drill-hole healing has not been identified. The transcription factor p53 suppresses osteoblast differentiation through inhibition of osterix expression. In present study, we demonstrate the effects of p53 deficiency on the capacity of MSCs and osteoblasts during drill-hole healing.

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This study aimed to investigate the accumulation and differentiation of mesenchymal stem cells (MSCs) around octacalcium phosphate (OCP) compared with those around calcium-deficient hydroxyapatite (CDHA), a material obtained through hydrolysis of the original OCP. Leptin receptor (Lepr)-expressing bone marrow-derived MSCs around the OCP and CDHA were pursued utilizing genetically modified Lepr-cre/Tomato mice. OCP and CDHA granules were implanted into the tibia defect of the mice for 10 weeks and subjected to histomorphometric and immunohistochemical analyses.

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Granulocyte colony stimulating factor (G-CSF), an essential cytokine regulating granulopoiesis, is expressed in a substantial proportion of breast cancers, and it has been implicated in cancer progression. Here, we examined effects of G-CSF on the development of bone metastases of breast cancer using immunocompetent mouse models. The expression of CXC chemokine ligand 12 (CXCL12) in bone marrow stromal cells, which plays a critical role in the maintenance of hematopoietic stem cells and also in cancer cell homing to bone, was markedly decreased in mice treated with G-CSF.

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Advances in intravital microscopy (IVM) have enabled the studies of cellular organization and dynamics in the native microenvironment of intact organisms with minimal perturbation. The abilities to track specific cell populations and monitor their interactions have opened up new horizons for visualizing cell biology in vivo, yet the success of standard fluorescence cell labeling approaches for IVM comes with a "dark side" in that unlabeled cells are invisible, leaving labeled cells or structures to appear isolated in space, devoid of their surroundings and lacking proper biological context. Here we describe a novel method for "filling in the void" by harnessing the ubiquity of extracellular (interstitial) fluid and its ease of fluorescence labelling by commonly used vascular and lymphatic tracers.

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Osteoblasts are the only cells that can give rise to bones in vertebrates. Thus, one of the most important functions of these metabolically active cells is mineralized matrix production. Because osteoblasts have a limited lifespan, they must be constantly replenished by preosteoblasts, their immediate precursors.

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Severe dental tissue damage induces odontoblast death, after which dental pulp stem and progenitor cells (DPSCs) differentiate into odontoblast-like cells, contributing to reparative dentin. However, the damage-induced mechanism that triggers this regeneration process is still not clear. We aimed to understand the effect of odontoblast death without hard tissue damage on dental regeneration.

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Bone-resorbing osteoclasts are regulated by the relative ratio of the differentiation factor, receptor activator NF-kappa B ligand (RANKL) and its decoy receptor, osteoprotegerin (OPG). Dental tissue-localized-resorbing cells called odontoclasts have regulatory factors considered as identical to those of osteoclasts; however, it is still unclear whether the RANKL/OPG ratio is a key factor for odontoclast regulation in dental pulp. Here, we showed that odontoclast regulators, macrophage colony-stimulating factor-1, RANKL, and OPG were detectable in mouse pulp of molars, but OPG was dominantly expressed.

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Objectives: Osteoclasts are induced by macrophage colony-stimulating factor-1 (CSF-1) and receptor activator of nuclear factor-κB (RANK) ligand (RANKL). Monocyte/macrophage lineages are thought to be osteoclast precursors; however, such cells have not been fully characterized owing to a lack of tools for their identification. Osteoclast precursors express colony-stimulating factor-1 receptor (CSF-1R) and RANK.

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Background: The periodontal ligament (PDL), which surrounds the tooth root, contains mesenchymal stem cells (MSCs) capable of differentiating into osteoblasts, cementoblasts, and fibroblasts under normal conditions. These MSCs are thought to have important roles in the repair and regeneration of injured periodontal tissues. However, since there is no useful marker for MSCs in the PDL, the characteristics and distributions of these cells remain unclear.

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Article Synopsis
  • Intermittent parathyroid hormone (iPTH) treatment promotes the formation of new bone cells, helping to reverse bone loss caused by osteoporosis, although the exact mechanisms are not fully understood.
  • Studies using mouse models showed that iPTH treatment leads to the differentiation of bone marrow mesenchymal stem cells (MSPCs) into mature osteoblasts, which are essential for bone formation.
  • iPTH not only increases the number of mature osteoblasts but also inhibits the formation of fat cells from MSPCs, suggesting it reprograms these cells to support bone health over fat accumulation in the bone marrow.
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Bone morphogenetic protein 2 (BMP-2) is widely known as a potent growth factor that promotes bone formation. However, an increasing number of studies have demonstrated side effects of BMP-2 therapy. A deeper understanding of the effect of BMP-2 on cells other than those involved directly in bone remodeling is of fundamental importance to promote a more effective delivery of BMP-2 to patients.

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