Faculty Profiles - SAKAI Kiyoshi

Papers - SAKAI Kiyoshi

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Implant-supported fixed prostheses with cantilever: a systematic review and meta-analysis. Reviewed International journal

Kondo Y, Sakai K, Minakuchi H, Horimai T, Kuboki T, JSOI Clinical Guideline Working Group collaborators

International journal of implant dentistry Vol. 10 ( 1 ) page： 57 2024.11

Conditioned medium of human mesenchymal stem cells affects stem cell senescence in osteoporosis. Reviewed International coauthorship International journal

Liu K, Sakai K, Watanabe J, Dong J, Maruyama H, Li X, Hibi H

Biochemical and biophysical research communications Vol. 711 page： 149858 2024.4

Cytoprotective role of human dental pulp stem cell-conditioned medium in chemotherapy-induced alopecia. Reviewed International journal

Chen H, Yamaguchi S, Wang Y, Kaminogo K, Sakai K, Hibi H

Stem cell research & therapy Vol. 15 ( 1 ) page： 84 2024.3

Cellular senescence is associated with osteonecrosis of the femoral head while mesenchymal stem cell conditioned medium inhibits bone collapse. Reviewed International journal

Okamoto M, Nakashima H, Sakai K, Takegami Y, Osawa Y, Watanabe J, Ito S, Hibi H, Imagama S

Scientific reports Vol. 14 ( 1 ) page： 3329 2024.2

Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：Scientific Reports

Osteonecrosis of the femoral head (ONFH) is a type of ischemic osteonecrosis that causes pain, loss of function, and femoral head collapse. Here, we analyzed samples of femoral heads excised from patients with ONFH to clarify the relationship between ischemic osteonecrosis and cellular senescence. X-gal staining was strong and p16INK4a-positive cells were abundant in the transitional region of ONFH. The β-galactosidase-positive cells in the transitional region were also positive for nestin, periostin, or DMP-1. In contrast, no β-galactosidase-positive cells were detected in the healthy region. The senescence-associated p16INK4a, p21, and p53 were upregulated in ONFH tissue. We also examined and analyzed a mouse ischemic femoral osteonecrosis model in vivo to verify the association between ONFH and cellular senescence. Human mesenchymal stem cell-conditioned medium (MSC-CM) was administered to determine its therapeutic efficacy against cellular senescence and bone collapse. MSC-CM reduced the number of senescent cells and downregulated the aforementioned senescence-related genes. It also decreased the number of empty lacunae 4 weeks after ischemia induction and promoted bone formation. At 6 weeks post-surgery, MSC-CM increased the trabecular bone volume, thereby suppressing bone collapse. We conclude that cellular senescence is associated with ONFH and that MSC-CM suppresses bone collapse in this disorder.

DOI： 10.1038/s41598-024-53400-w

Scopus

PubMed

Langerhans cell histiocytosis of single-system multifocal bone, including the mandible, in a 22-month-old child: A case report Reviewed International journal

Kiyoshi Sakai, Noriyuki Yamamoto, Satoshi Yamaguchi, Kazuto Okabe, Yoshiro Koma, Hideharu Hibi

Oral Science International 2022.6

Dental pulp stem cell-derived small extracellular vesicle in irradiation-induced senescence Reviewed International coauthorship International journal

Dong Jiao, Sakai Kiyoshi, Koma Yoshiro, Watanabe Junna, Liu Kehong, Maruyama Hiroshi, Sakaguchi Kohei, Hibi Hideharu

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS Vol. 575 page： 28 - 35 2021.10

Conditioned medium from stem cells derived from human exfoliated deciduous teeth ameliorates NASH via the Gut-Liver axis. Reviewed International journal

Muto H, Ito T, Tanaka T, Yokoyama S, Yamamoto K, Imai N, Ishizu Y, Maeda K, Honda T, Ishikawa T, Kato A, Ohshiro T, Kano F, Yamamoto A, Sakai K, Hibi H, Ishigami M, Fujishiro M

Scientific reports Vol. 11 ( 1 ) page： 18778 2021.9

Coexistence of Sjogren's syndrome and bilateral ranulas: A case report and review of the literature Reviewed International journal

Koma Yoshiro, Fujimoto Takehiro, Sakai Kiyoshi, Sugimura Yukiko, Yamaguchi Satoshi, Hibi Hideharu

ORAL SCIENCE INTERNATIONAL 2021.9

Language：English Publishing type：Research paper (scientific journal) Publisher：Oral Science International

Sjögren's syndrome and ranulas are relatively frequently occurring diseases. However, when they occur simultaneously, its clinical features and pathogenesis remain unclear. Here, we report a patient with bilateral ranulas. Magnetic resonance imaging at diagnosis revealed a “salt and pepper” appearance in bilateral parotid glands, leading a diagnosis of asymptomatic Sjögren's syndrome. She was successfully treated with excision of the left sublingual gland and sclerotherapy. A literature review suggests that this coexistence may not be very rare. In addition, it may be characterized by a high prevalence of bilateral ranulas.

DOI： 10.1002/osi2.1121

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Scopus

Hyperparathyroidism-jaw tumor syndrome with bilateral ossifying fibromas in the mandible: A case report Reviewed International journal

Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology 2021.7

Extracellular Vesicles of Stem Cells to Prevent BRONJ Reviewed International journal

Watanabe J, Sakai K, Urata Y, Toyama N, Nakamichi E, Hibi H

Journal of Dental Research Vol. 99 ( 5 ) page： 552 - 560 2020.5

先天性無フィブリノゲン血症患者の抜歯術における周術期管理を行った1例 Reviewed

岡部一登, 土屋周平, 酒井陽, 松下義泰, 杉本圭佑, 日比英晴

日本口腔外科学会雑誌 Vol. 65 ( 8 ) page： 507 - 512 2019.8

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：(公社)日本口腔外科学会

13歳男子。右下6番根尖性歯周炎に起因した下顎骨骨膜下膿瘍および頬部蜂窩織炎と診断した。先天性無フィブリノゲン(Fbg)血症のため消炎処置前にFbg製剤2gを投与し、歯肉の腫脹部より膿瘍切開術を施行した。同日よりアモキシシリン投与を開始し、翌日より切開部からの洗浄を継続し、7日後には顎下部や口腔内の腫脹は消退した。翌月に右下6番を抜歯し、抜歯後は事前に製作した創部保護床を終日装着させた。Fbg製剤は血中Fbg濃度100mg/dL以上を目標に抜歯当日3g、抜歯後1日目に2g、抜歯後2日目に2g投与した。抜歯後2日目には抜歯窩の縫合糸は脱落していたが幼若な血餅で満たされ、引き続き創部保護床は終日装着したままとして退院した。抜歯後8日目に創部保護床を除去し、処置後の異常出血はなく、治癒の遅延も認めなかった。

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Identification of the Novel Tooth-Specific Transcription Factor AmeloD Reviewed International coauthorship

He B, Chiba Y, Li H, de Vega S, Tanaka K, Yoshizaki K, Ishijima M, Yuasa K, Ishikawa M, Rhodes C, Sakai K, Zhang P, Fukumoto S, Zhou X, Yamada Y

Journal of Dental Research Vol. 98 ( 2 ) page： 234 - 241 2019.2

Dental pulp-derived stem cell conditioned medium to regenerate peripheral nerves in a novel animal model of dysphagia. Reviewed International journal

Takeshi Tsuruta, Kiyoshi Sakai, Junna Watanabe, Wataru Katagiri, Hideharu Hibi

PLOS ONE Vol. 13 ( 12 ) page： e0208938 2018.12

Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal)

In nerve regeneration studies, various animal models are used to assess nerve regeneration. However, because of the difficulties in functional nerve assessment, a visceral nerve injury model is yet to be established. The superior laryngeal nerve (SLN) plays an essential role in swallowing. Although a treatment for SLN injury following trauma and surgery is desirable, no such treatment is reported in the literature. We recently reported that stem cells derived from human exfoliated deciduous teeth (SHED) have a therapeutic effect on various tissues via macrophage polarization. Here, we established a novel animal model of SLN injury. Our model was characterized as having weight loss and drinking behavior changes. In addition, the SLN lesion caused a delay in the onset of the swallowing reflex and gain of laryngeal residue in the pharynx. Systemic administration of SHED-conditioned media (SHED-CM) promoted functional recovery of the SLN and significantly promoted axonal regeneration by converting of macrophages to the anti-inflammatory M2 phenotype. In addition, SHED-CM enhanced new blood vessel formation at the injury site. Our data suggest that the administration of SHED-CM may provide therapeutic benefits for SLN injury.

DOI： 10.1371/journal.pone.0208938

他家骨髄由来間葉系細胞の移植による骨再生の検討

渡邊純奈, 片桐渉, 大杉将嗣, 酒井陽, 岡部一登, 椙村有紀子, 坂口晃平, 鶴田剛士, 日比英晴

日本口腔インプラント学会誌 Vol. 31 ( 2 ) page： E75 - E75 2018.6

Mediator 1 Contributes to Enamel Mineralization as a Coactivator for Notch1 Signaling and Stimulates Transcription of the Alkaline Phosphatase Gene Reviewed International coauthorship

Keigo Yoshizaki, Lizhi Hu, Thai Nguyen, Kiyoshi Sakai, Masaki Ishikawa, Ichiro Takahashi, Satoshi Fukumoto, Pamela Den Besten, Daniel D. Bikle, Yuko Oda, Yoshihiko Yamada

JOURNAL OF BIOLOGICAL CHEMISTRY Vol. 292 ( 33 ) page： 13531-13540 2017.8

ラット末梢性嚥下障害モデルを用いた乳歯歯髄幹細胞由来成長因子の治療効果の検討 International journal

鶴田剛士, 片桐渉, 大杉将嗣, 酒井陽, 若山有紀子, 坂口晃平, 渡邊純奈, 日比英晴

日本口腔科学会雑誌 Vol. 66 ( 2 ) page： 207 - 208 2017.7

Pannexin 3 and connexin 43 modulate skeletal development through their distinct functions and expression patterns Reviewed International coauthorship International journal

Masaki Ishikawa, Geneva L. Williams, Tomoko Ikeuchi, Kiyoshi Sakai, Satoshi Fukumoto, Yoshihiko Yamada

JOURNAL OF CELL SCIENCE Vol. 129 ( 5 ) page： 1018 - 1030 2016.3

Language：English Publishing type：Research paper (scientific journal) Publisher：COMPANY OF BIOLOGISTS LTD

Pannexin 3 (Panx3) and connexin 43 (Cx43; also known as GJA1) are two major gap junction proteins expressed in osteoblasts. Here, we studied their functional relationships in skeletal formation by generating Panx3(-/-) and Panx3(-/-); Cx43(-/-) mice and comparing their skeletal phenotypes with Cx43(-/-) mice. Panx3(-/-) mice displayed defects in endochondral and intramembranous ossification, resulting in severe dwarfism and reduced bone density. The skeletal abnormalities of Panx3(-/-); Cx43(-/-) mice were similar to those in Panx3(-/-) mice. The gross appearance of newborn Cx43(-/-) skeletons showed no obvious abnormalities, except for less mineralization of the skull. In Panx3(-/-) mice, proliferation of chondrocytes and osteoblasts increased and differentiation of these cells was inhibited. Panx3 promoted expression of osteogenic proteins such as ALP and Ocn (also known as ALPL and BGLAP, respectively), as well as Cx43, by regulating Osx (also known as SP7) expression. Panx3 was induced in the early differentiation stage and reduced during the maturation stage of osteoblasts, when Cx43 expression increased in order to promote mineralization. Furthermore, only Panx3 functioned as an endoplasmic reticulum (ER) Ca2+ channel to promote differentiation, and it could rescue mineralization defects in Cx43(-/-) calvarial cells. Our findings reveal that Panx3 and Cx43 have distinct functions in skeletal formation.

DOI： 10.1242/jcs.176883

Dopaminergic differentiation of stem cells from human deciduous teeth and their therapeutic benefits for Parkinsonian rats Reviewed International journal

Hiromi Fujii, Kohki Matsubara, Kiyoshi Sakai, Mikako Ito, Kinji Ohno, Minoru Ueda, Akihito Yamamoto

BRAIN RESEARCH Vol. 1613 page： 59 - 72 2015.7

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCIENCE BV

Parkinson's disease (PD) is a progressive neurodegenerative disorder caused by the loss of nigrostriatal dopaminergic (DAergic) neurons and the depletion of striatal dopamine. Here we show that DAergic-neuron-like cells could be efficiently induced from stem cells derived from human exfoliated deciduous teeth (SHEDS), and that these induced cells had therapeutic benefits in a 6-OHDA-induced Parkinsonian rat model. In our protocol, EGF and bFGF signaling activated the SHED's expression of proneural genes, Ngn2 and Mash1, and subsequent treatment with brain-derived neurotrophic factor (BDNF) promoted their maturation into DAergic neuron-like SHEDs (dSHEDs). A hypoxic DAergic differentiation protocol improved cell viability and enhanced the expression of multiple neurotrophic factors, including BDNF, GDNF, NT-3, and HGF. Engrafted dSHEDs survived in the striatum of Parldnsonian rats, improved the DA level more efficiently than engrafted undifferentiated SHEDs, and promoted the recovery from neurological deficits. Our findings further suggested that paracrine effects of dSHEDs contributed to neuroprotection against 6-OHDA-induced neurodegeneration and to nigrostriatal tract restoration. In addition, we found that the conditioned medium derived from dSHEDs protected primary neurons against 6-OHDA toxicity and accelerated neurite outgrowth in vitro. Thus, our data suggest that stem cells derived from dental pulp may have therapeutic benefits for PD. (C) 2015 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.brainres.2015.04.001

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Secreted Ectodomain of Sialic Acid-Binding Ig-Like Lectin-9 and Monocyte Chemoattractant Protein-1 Promote Recovery after Rat Spinal Cord Injury by Altering Macrophage Polarity Reviewed International journal

Kohki Matsubara, Yoshihiro Matsushita, Kiyoshi Sakai, Fumiya Kano, Megumi Kondo, Mariko Noda, Noboru Hashimoto, Shiro Imagama, Naoki Ishiguro, Akio Suzumura, Minoru Ueda, Koichi Furukawa, Akihito Yamamoto

JOURNAL OF NEUROSCIENCE Vol. 35 ( 6 ) page： 2452 - 2464 2015.2

Language：English Publishing type：Research paper (scientific journal) Publisher：SOC NEUROSCIENCE

Engrafted mesenchymal stem cells from human deciduous dental pulp (SHEDs) support recovery from neural insults via paracrine mechanisms that are poorly understood. Here we show that the conditioned serum-free medium (CM) from SHEDs, administered intrathecally into rat injured spinal cord during the acute postinjury period, caused remarkable functional recovery. The ability of SHED-CM to induce recovery was associated with an immunoregulatory activity that induced anti-inflammatory M2-like macrophages. Secretome analysis of the SHED-CM revealed a previously unrecognized set of inducers for anti-inflammatory M2-like macrophages: monocyte chemoattractant protein-1 (MCP-1) and the secreted ectodomain of sialic acid-binding Ig-like lectin-9 (ED-Siglec-9). Depleting MCP-1 and ED-Siglec-9 from the SHED-CM prominently reduced its ability to induce M2-like macrophages and to promote functional recovery after spinal cord injury (SCI). The combination of MCP-1 and ED-Siglec-9 synergistically promoted the M2-like differentiation of bone marrow-derived macrophages in vitro, and this effect was abolished by a selective antagonist for CC chemokine receptor 2 (CCR2) or by the genetic knock-out of CCR2. Furthermore, MCP-1 and ED-Siglec-9 administration into the injured spinal cord induced M2-like macrophages and led to a marked recovery of hindlimb locomotor function after SCI. The inhibition of this M2 induction through the inactivation of CCR2 function abolished the therapeutic effects of both SHED-CM and MCP-1/ED-Siglec-9. Macrophages activated by MCP-1 and ED-Siglec-9 extended neurite and suppressed apoptosis of primary cerebellar granule neurons against the neurotoxic effects of chondroitin sulfate proteoglycans. Our data suggest that the unique combination of MCP-1 and ED-Siglec-9 repairs the SCI through anti-inflammatory M2-like macrophage induction.

DOI： 10.1523/JNEUROSCI.4088-14.2015

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Epiprofin orchestrates epidermal keratinocyte proliferation and differentiation Reviewed International journal

Takashi Nakamura, Yasuo Yoshitomi, Kiyoshi Sakai, Vyomesh Patel, Satoshi Fukumoto, Yoshihiko Yamada

JOURNAL OF CELL SCIENCE Vol. 127 ( 24 ) page： 5261 - 5272 2014.12

Language：English Publishing type：Research paper (scientific journal) Publisher：COMPANY OF BIOLOGISTS LTD

The basal layer of the epidermis contains stem cells and transit amplifying cells that rapidly proliferate and differentiate further into the upper layers of the epidermis. A number of molecules have been identified as regulators of this process, including p63 (also known as tumor protein 63) and Notch1. However, little is known about the mechanisms that regulate the transitions from stem cell to proliferating or differentiating transit amplifying cell. Here, we demonstrate that epiprofin (Epfn, also known as Sp6) plays crucial distinct roles in these transition stages as a cell cycle regulator and a transcription factor. Epfn knockout mice have a thickened epidermis, in which p63-expressing basal cells form multiple layers owing to the accumulation of premature transit amplifying cells with reduced proliferation and a reduction in the number of differentiating keratinocytes expressing Notch1. We found that low levels of Epfn expression increased the proliferation of human immortalized keratinocyte (HaCaT) cells by increasing EGF responsiveness and superphosphorylation of Rb. By contrast, high levels of Epfn expression promoted cell cycle exit and differentiation, by reducing E2F transactivation and inducing Notch1 expression. Our findings identify multiple novel functions of Epfn in epidermal development.

DOI： 10.1242/jcs.156778

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Papers - SAKAI Kiyoshi