Naoyuki Chosa

Iwate Medical University · Department of Biochemistry, Division of Cellular Biosignal Sciences

Mesenchymal stem cells (MSCs) are involved in anti-inflammatory events and tissue repair; these functions are activated by their migration or homing to inflammatory tissues in response to various chemokines. However, the mechanism by which MSCs interact with other cell types in inflammatory tissue remains unclear. We investigated the role of period...

Human mesenchymal stem cells (hMSCs) remodel or regenerate various tissues through several mechanisms. Here, we identified the hMSC-secreted protein SCRG1 and its receptor BST1 as a positive regulator of self-renewal, migration, and osteogenic differentiation. SCRG1 and BST1 gene expression decreased during osteogenic differentiation of hMSCs. Intr...

The Toll receptor was originally identified as an indispensable molecule for Drosophila embryonic development and subsequently as an essential component of innate immunity from insects to humans. Although in Drosophila the Easter protease processes the pro-Spätzle protein to generate the Toll ligand during development, the identification of the pro...

The reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) by defined transcription factors has been a well-established technique and will provide an invaluable resource for regenerative medicine. However, the low reprogramming efficiency of human iPSC is still a limitation for clinical application. Here we showed that the repro...

Background Temporomandibular joint osteoarthritis (TMJ-OA) causes cartilage degeneration, bone cavitation, and fibrosis of the TMJ. However, the mechanisms underlying the fibroblast-like synoviocyte (FLS)-mediated inflammatory activity in TMJ-OA remain unclear. Methods and results Reverse transcription-quantitative polymerase chain reaction analys...

Objectives Temporomandibular joint osteoarthritis (TMJ-OA) is a multifactorial disease caused by inflammation and oxidative stress. It has been hypothesized that mechanical stress-induced injury of TMJ tissues induces the generation of reactive oxygen species (ROS), such as hydroxyl radical (OH∙), in the synovial fluid (SF). In general, the overpro...

Background Temporomandibular joint osteoarthritis (TMJ-OA) causes cartilage degeneration, bone cavitation, and fibrosis of the TMJ. However, the mechanisms underlying the fibroblast-like synoviocyte (FLS)-mediated inflammatory activity in TMJ-OA remain unclear. Methods and Results Reverse transcription-quantitative polymerase chain reaction analysi...

Osteoarthritis (OA)-related fibrosis is a possible cause of temporomandibular joint (TMJ) stiffness. However, the molecular mechanisms underlying the fibrogenic activity in fibroblast-like synoviocytes (FLSs) remain to be clarified. The present study examined the effects of receptor tyrosine kinase (RTK) ligands, such as fibroblast growth factor (F...

Mechanosensitive (MS) neurons in the periodontal ligament (PDL) pass information to the trigeminal ganglion when excited by mechanical stimulation of the tooth. During occlusal tooth trauma of PDL tissues, MS neurons are injured, resulting in atrophic neurites and eventual degeneration of MS neurons. Nerve growth factor (NGF), a neurotrophic factor...

Many inflammatory cells are known to home to inflamed temporomandibular joint (TMJ) tissues by stimulation with cytokines and chemokines produced by inflammatory lesions in the TMJ. However, how the inflammatory cells affect the progression of inflammation in TMJ synovial tissues after their homing to inflamed TMJ site is still uncertain. Here, we...

Surface pre-reacted glass‑ionomer (S‑PRG)-containing dental materials, including composite and coating resins have been used for the restoration and/or prevention of dental cavities. S‑PRG is known to have the ability to release aluminum, boron, fluorine, silicon, and strontium ions. Aluminum ions are known to be inhibitors whereas boron, fluorine,...

Mesenchymal stem cells (MSCs) retain the ability to self-renew and differentiate into mesenchymal cells. Therefore, human MSCs are suitable candidates for use in regenerative medicine and cell therapies. Upon activation by tissue damage, MSCs contribute to tissue repair through a multitude of processes such as self-renewal, migration, and different...

Immunosuppressive/anti-inflammatory macrophage (Mφ), M2-Mφ that expressed the typical M2-Mφs marker, CD206, and anti-inflammatory cytokine, interleukin (IL)-10, is beneficial and expected tool for the cytotherapy against inflammatory diseases. Here, we demonstrated that bone marrow-derived lineage-positive (Lin+) blood cells proliferated and differ...

Recently, we identified the scrapie responsive gene 1 (SCRG1) secreted from mesenchymal stem cells (MSCs) and its receptor bone marrow stromal cell antigen 1 (BST1) as positive regulators of stem cell qualities such as self‑renewal, migration abilities, and osteogenic differentiation potential. Here, we examined the effect of the paracrine activity...

Malocclusion caused by abnormal jaw development or muscle overuse during mastication results in abnormal mechanical stress to the tissues surrounding the temporomandibular joint (TMJ). Excessive mechanical stress against soft and hard tissues around the TMJ is involved in the pathogenesis of inflammatory diseases, including osteoarthritis (OA). OA-...

The Wilms’ tumor 1 gene (WT1) was originally isolated and described as the gene responsible for Wilms’ tumor. Although there is growing evidence linking the overexpression of WT1 to tumorigenesis, no reports on ameloblastoma are available at present. The aim of this study was to examine the expression of WT1 in various histological subtypes of amel...

Bisphosphonates (BPs) are analogues of pyrophosphate that are known to prevent bone resorption by inhibiting osteoclast activity. Nitrogen-containing BPs, such as zoledronic acid (ZA), are widely used in the treatment of osteoporosis and bone metastasis. However, despite having benefits, ZA has been reported to induce BP-related osteonecrosis of th...

The direction of mesenchymal stem cell (MSC) differentiation is regulated by stimulation with various growth factors and cytokines. We recently established MSC lines, [transforming growth factor-β (TGF-β)-responsive SG‑2 cells, bone morphogenetic protein (BMP)-responsive SG‑3 cells, and TGF-β/BMP-non-responsive SG‑5 cells], derived from the bone ma...

Cytokines and their intercellular signals regulate the multipotency of mesenchymal stem cells (MSCs). The present study established the MSC lines SG‑2, ‑3, and ‑5 from the bone marrow of green fluorescent protein (GFP)‑transgenic mice. These cell lines clearly expressed mouse MSC markers Sca‑1 and CD44, and SG‑2 and ‑5 cells retained the potential...

Transgenic mice that overexpress the red fluorescent protein tdTomato (tdTomato mice) are well suited for use in regenerative medicine studies. Cultured cells from this murine model exhibit strong red fluorescence, enabling real‑time in vivo imaging through the body surface of grafted animals. Mesenchymal stem cells (MSCs) have marked potential for...

Dental pulp cells (DPCs), including dental pulp (DP) stem cells, play a role in dentine repair under certain conditions caused by bacterial infections associated with caries, tooth fracture and injury. Mesenchymal stem cells (MSCs) have also been shown to be involved in this process of repair. However, the mechanisms through which MSCs are recruite...

The purpose of this study was to track the fate of GFP-labeled transgenic mouse mesenchymal stem cells (MSC) transplanted in nude mice. Mouse MSC had been collected from tibia of whole body GFP-labeled mice; were transplanted into five nude mice by tail vein injection; and were fed for 4 weeks. After comfort sacrifice, the existence and accumulatio...

The laccase in the pupal cuticle of the silkworm, Bombyx mori, is thought to accumulate as an inactive precursor that can be activated stage-dependently. In this study we isolated an 81-kDa laccase from cuticular extract of B. mori that was prepared by digestion of the pupal cuticles with α-chymotrypsin. The mass spectrometric analysis of the purif...

Cell-cell adhesions induce various intracellular signals through hierarchical and synergistic molecular interactions. Recently, we demonstrated that a high cell density induces the expression of vascular cell adhesion molecule-1 (VCAM-1) through the nuclear factor-κB (NF-κB) pathway in human bone marrow-derived mesenchymal stem cells (MSCs). Howeve...

Transforming growth factor-β (TGF-β) is a critical regulator of osteogenic differentiation and the platelet-derived growth factor (PDGF) is a chemoattractant or mitogen of osteogenic mesenchymal cells. However, the combined effects of these regulators on the osteogenic differentiation of mesenchymal cells remains unknown. In this study, we investig...

The effects of tongue cleaning on reconstruction of bacterial flora in dental plaque and tongue coating itself are obscure. We assessed changes in the amounts of total bacteria as well as Fusobacterium nucleatum in tongue coating and dental plaque specimens obtained with and without tongue cleaning. We conducted a randomized examiner-blind crossove...

Human mesenchymal stem cells (hMSCs) remodel or regenerate various tissues through several mechanisms. Here, we identified the hMSC-secreted protein SCRG1 and its receptor BST1 as a positive regulator of self-renewal, migration, and osteogenic differentiation. SCRG1 and BST1 gene expression decreased during osteogenic differentiation of hMSCs. Intr...

The development of new osteoconductive bone substitute materials is expected in medicine. In this study, we attempted to produce new hydroxylapatite (HAP)/collagen (Col) composites using two HAP particles of different sizes and porcine type I collagen. The two HAP particles were either nano-sized (40 nm in average diameter; n-HAP) or had macro-pore...

Background/Aims: Remodeling of fibrous and vascular tissues in the periodontal ligament (PDL) around the tooth root was observed during tooth movement by orthodontic force application. We previously demonstrated that a single cell-derived culture (SCDC) of primarily cultured PDL fibroblasts, called SCDC2, has an endothelial progenitor cell (EPC)-li...

Objective: We examined bacteria levels in dental plaque and tongue coating before and after their removal. Method: Tongue coating samples were collected from 18 systemic healthy subjects (mean 22.9±3.6 years old) with 3 strokes of a micro-spatula. Subsequently, dental plaque was removed from the first molar and second premolar lingual surfaces on...

We investigated whether transforming growth factor-β1 (TGF-β1) promoted the epithelial-mesenchymal transition (EMT) and migration of human oral squamous cell carcinoma (hOSCC) cells. Among the 6 hOSCC cell lines investigated, Smad2 phosphorylation and TGF-β target genes expression were most clearly upregulated following TGF-β1 stimulation in HSC-4...

Caveolin-1 (Cav-1) is a membrane protein. Recently, it has been reported that secreted Cav-1 induces angiogenesis in inflammatory microenvironment. However, it is unclear that Cav-1 regulates gingival inflammation. Therefore, we investigated the Cav-1 function to periodontal cells. Expression of Cav-1 in human periodontitis tissues was examined pat...

Internleukin-1 (IL-1) and IL-6 are the most potent proinflammatory cytokines being involved in inflammatory diseases such as periodontitis. The objective of this study was to examine the synergistic effects of IL-1β and IL-6 on gingival inflammation by targeting cultured human gingival fibroblasts (HGFs). HGFs were treated with IL-1β or IL-6/solubl...

J Oral Pathol Med (2013)42: 133–139 Background: The product of the Wilms’ tumor gene, WT1 protein, is a tumor antigen for various kinds of cancer, and WT1 peptide-based cancer immunotherapy is widely anticipated as a new possibility for cancer treatment. The aim of this study was to investigate the expression of WT1 from quantitative and morphologi...

Fig.S1 - TGF-β2 and TGF-β3 inhibit the growth of PDL-derived EPC-like fibroblastic cells. Fig.S2 - TGF-β2 and TGF-β3 induce the expression of SMC markers (α-SMA, h1-calponin) but suppress the expression of EC marker (Tie-2) in PDL-derived EPC-like fibroblastic cells.

The aim of this study was to characterize the expression status of cadherins in dental pulp-derived mesenchymal progenitor/stem cells from deciduous and permanent teeth, and to determine how cadherins affect the multipotency of the progenitor/stem cells. We evaluated and compared the expression status of cadherins in dental pulp-derived cells from...

The periodontal ligament (PDL) is a fibrous connective tissue that attaches the tooth to the alveolar bone. We previously demonstrated the ability of PDL fibroblast-like cells to construct an endothelial cell (EC) marker-positive blood vessel-like structure, indicating the potential of fibroblastic lineage cells in PDL tissue as precursors of endot...

Stromal cell-derived factor (SDF)-1α has been reported to play a crucial role in stem cell homing and recruitment to injured sites. However, no information is available about its role in periodontal tissues. The aim of this in vitro study was to investigate the effects of basic fibroblast growth factor (FGF-2) and transforming growth factor (TGF)-β...

Although cells derived from periodontal ligament (PDL) tissue are reported to have stem cell-like activity and are speculated to play a crucial role for tissue healing and regeneration after injury or orthodontic treatment, mechanisms regulating their recruitment and activation remain unknown. Recently, stromal cell-derived factor 1α (SDF-1α) has b...

The periodontal ligament (PDL) is a fibrous connective tissue located between the tooth root and the alveolar bone. We previously demonstrated that a single cell-derived culture of primarily cultured PDL fibroblasts has the potential to construct an endothelial cell (EC) marker-positive blood vessel-like structure, suggesting that the fibroblastic...

Recently, many studies have shown that mesenchymal stem cells (MSCs) exist in dental pulp and periodontal ligament (PDL) of human deciduous teeth. MSCs derived from extracted teeth have been considered an appropriate candidate for not only dental tissue regeneration but also for the treatment of general diseases. However, there was no immortal PDL...

Both periodontal ligament tissue that located between the alveolar bone and the root of teeth and dental pulp tissue are reported to have mesenchymal stem cells [1, 2] (MSCs). MSCs are considered to be involved in the homeostasis of periodontal tissue. Recent studies have revealed that the stromal cell-derived factor-1α (SDF-1) is crucial for migra...

The contribution of plasminogen (Plg)/plasmin, which have claimed to be the main fibrinolytic regulators in the bone metabolism, remains unclear. This study evaluated how the absence of Plg affects the function of osteoblast (OB) and osteoclast (OC). There was a larger population of pre-OCs in bone marrow-derived cells from the Plg−/− mice than the...

The contribution of plasminogen (Plg)/plasmin, which have claimed to be the main fibrinolytic regulators in the bone metabolism, remains unclear. This study evaluated how the absence of Plg affects the function of osteoblast (OB) and osteoclast (OC). There was a larger population of pre-OCs in bone marrow-derived cells from the Plg−/− mice than the...

MSCs (mesenchymal stem cells) migrate into damaged tissue and then proliferate and differentiate into various cell lineages to regenerate bone, cartilage, fat and muscle. Cell-cell adhesion of MSCs is essential for the MSC-dependent tissue regeneration after their homing into a damaged tissue. However, it remains to be elucidated what kinds of adhe...

Although periodontal ligament (PDL) cells have previously been isolated from permanent teeth, they have not been isolated from deciduous teeth. Here, we used human telomerase reverse transcriptase (hTERT) induction to establish the first immortalized PDL cell lines derived from deciduous teeth. Cells were transfected with plasmids containing hTERT....

a blood supply is crucial for tissue healing and regeneration. periodontal ligament (pdl) tissue is situated between the tooth root and alveolar bone, and cells derived from pdl tissue are reported to have stem cell-like activity. this study aimed to evaluate the potential of pdl cells derived from deciduous teeth to express endothelial cell (EC)-s...

although dental pulp (dp) cells are indispensable for repair after injury, and blood supply is crucial for tissue healing and regeneration, the potential of dp cells derived from deciduous teeth to express endothelial cell (EC)-specific markers has yet to be determined. therefore, this study inves-tigated mRNA expression of the EC-specific markers...

SYNOPSIS The purpose of this study was to evaluate gene expressions of human mesen-chymal stem cells (hMSC) cultured in osteogenic differentiation medium (OM) which contained ascorbic acid, β-glycerophosphate and dexamethasone for 0 (control), 3, 5, 7, 14 and 21 days by 8.5k Genome Focus DNA microarray and real-time PCR. It was confirmed by the DNA...

Fas-mediated cell death in a human salivary gland adenocarcinoma cell line (HSG) was induced by treatment of the cells with agonistic anti-Fas antibody (CH-11), and this cell death was enhanced by pretreatment with tumor necrosis factor alpha (TNF-alpha). The mode of cell death was apoptosis, because it was accompanied by caspase activation and the...

Alkaline-heat-treated titanium self-forms an apatite surface layer in vivo. The aim of the present study was to materialistically characterize the surface of alkaline-heat-treated titanium immersed in simulated body fluid (AHS-TI) and to examine the differentiation behavior of osteoblasts on AHS-TI. SEM, thin-film XRD, FTIR, and XPS analyses reveal...

It has been reported that heat shock protein (HSP) 90 is involved in the regulation of signaling cascades including those resulting in cell proliferation and apoptosis. However, little is known about how HSP90 affects apoptosis signaling. In this study, using a specific inhibitor of HSP90, geldanamycin (GDM), we investigated the relationship betwee...