研究者詳細 - WANG ZIYI

論文 - WANG ZIYI

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Gingipain regulates isoform switches of PD-L1 in macrophages infected with Porphyromonas gingivalis 査読国際共著国際誌

15 ( 1 ) 2025年3月

担当区分：筆頭著者記述言語：英語掲載種別：研究論文（学術雑誌）

Abstract
Periodontal pathogen Porphyromonas gingivalis (P. gingivalis) is believed to possess immune evasion capabilities, but it remains unclear whether this immune evasion is related to host gene alternative splicing (AS). In this study, RNA-sequencing revealed significant changes in both AS landscape and transcriptomic profile of macrophages following P. gingivalis infection with/without knockout of gingipain (a unique toxic protease of P. gingivalis). P. gingivalis infection increased the PD-L1 transcripts expression and selectively upregulated a specific coding isoform that more effectively binds to PD-1 on T cells, thereby inhibiting immune function. Biological experiments also detected AS switch of PD-L1 in P. gingivalis-infected or gingipain-treated macrophages. AlphaFold 3 predictions indicated that the protein docking compatibility between PD-1 and P. gingivalis-upregulated PD-L1 isoform was over 80% higher than another coding isoform. These findings suggest that P. gingivalis employs gingipain to modulate the AS of PD-L1, facilitating immune evasion.

Yilin Zheng and Ziyi Wang have contributed equally to this work.

DOI： 10.1038/s41598-025-94954-7

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その他リンク： https://www.nature.com/articles/s41598-025-94954-7

O‐<scp>GlcNAcylation</scp> regulates osteoblast differentiation through the morphological changes in mitochondria, cytoskeleton, and endoplasmic reticulum 査読国際共著国際誌

Yao Weng, Ziyi Wang, Heriati Sitosari, Mitsuaki Ono, Hirohiko Okamura, Toshitaka Oohashi

BioFactors 2024年10月

Filamin A mediates embryonical palatal fusion by linking mechanotransduction with β-Catenin/Smad2 国際共著

Ziyi Wang, Satoru Hayano, Yao Weng, Xindi Mu, Mitsuaki Ono, Jeremie Oliver Piña, Rena N. D'Souza, Takashi Yamashiro, Toshitaka Oohashi, Hiroshi Kamioka

bioRxiv 2024年2月

担当区分：筆頭著者,　責任著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Cold Spring Harbor Laboratory

To decipher potential mechanisms underlying cleft palate (CP), we used advanced bioinformatic integrated with literature mining and genome-wide association study (GWAS). Re-analysis of RNA-seq data (GSE45568, GSE185279) combined with literature mining highlighted the roles of Filamin A (Flna) and Epithelial-Mesenchymal Transition (EMT) in palatal development. Immunofluorescence of in vivo palatal shelves showed increased Flna in medial edge epithelial (MEE) cells and EMT cells located in an epithelial triangle. Inhibition of TGF-β or RhoA and mechanical stimuli impacted Flna expression in ex vivo cultured palatal shelves. Re-analysis of scRNA-seq data (GSE155928) highlighted a correlation between Flna and Ctnnb1 in EMT cells. Flna knockdown affected β-catenin/Smad2 expression in cultured palatal shelves and HaCaT cells. Epithelium-specific knockout of Flna delayed palatal fusion in female mice but not males. Mendelian randomization analysis suggested that parental habitual physical activity (HPA) was causally associated with lower risk of CP in their offspring. Together, these findings suggested that parental HPA could benefit their offspring's palatal development through Flna by linking mechanotransduction with the Wnt/TGF-β/Smad signaling pathways during palatal fusion.

DOI： 10.1101/2024.02.16.580664

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Changes in the intra- and peri-cellular sclerostin distribution in lacuno-canalicular system induced by mechanical unloading 査読国際誌

Ryuta Osumi, Ziyi Wang, Yoshihito Ishihara, Naoya Odagaki, Tadahiro Iimura, Hiroshi Kamioka

Journal of Bone and Mineral Metabolism 39 ( 2 ) 148 - 159 2021年3月

Loading history changes the morphology and compressive force-induced expression of receptor activator of nuclear factor kappa B ligand/osteoprotegerin in MLO-Y4 osteocytes 査読国際誌

Ziyi Wang, Yao Weng, Yoshihito Ishihara, Naoya Odagaki, Ei Ei Hsu Hlaing, Takashi Izawa, Hirohiko Okamura, Hiroshi Kamioka

PeerJ 8 2020年11月

担当区分：筆頭著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：PeerJ

Abstract

Background
In this study, we investigated the effect of the mechanical loading history on the expression of receptor activator of nuclear factor kappa B ligand (RANKL) and osteoprotegerin (OPG) in MLO-Y4 osteocyte-like cells.

Methods
Three hours after MLO-Y4 osteocytes were seeded, a continuous compressive force (CCF) of 31 dynes/cm2 with or without additional CCF (32 dynes/cm2) was loaded onto the osteocytes. After 36 h, the additional CCF (loading history) was removed for a recovery period of 10 h. The expression of RANKL, OPG, RANKL/OPG ratio, cell numbers, viability and morphology were time-dependently examined at 0, 3, 6 and 10 h. Then, the same additional CCF was applied again for 1 h to all osteocytes with or without the gap junction inhibitor to examine the expression of RANKL, OPG, the RANKL/OPG ratio and other genes that essential to characterize the phenotype of MLO-Y4 cells. Fluorescence recovery after photobleaching technique was also applied to test the differences of gap-junctional intercellular communications (GJIC) among MLO-Y4 cells.

Results
The expression of RANKL and OPG by MLO-Y4 osteocytes without a loading history was dramatically decreased and increased, respectively, in response to the 1-h loading of additional weight. However, the expression of RANKL, OPG and the RANKL/OPG ratio were maintained at the same level as in the control group in the MLO-Y4 osteocytes with a loading history but without gap junction inhibitor treatment. Treatment of loading history significantly changed the capacity of GJIC and protein expression of connexin 43 (Cx43) but not the mRNA expression of Cx43. No significant difference was observed in the cell number or viability between the MLO-Y4 osteocyte-like cells with and without a loading history or among different time checkpoints during the recovery period. The cell morphology showed significant changes and was correlated with the expression of OPG, Gja1 and Dmp1 during the recovery period.

Conclusion
Our findings indicated that the compressive force-induced changes in the RANKL/OPG expression could be habituated within at least 11 h by 36-h CCF exposure. GJIC and cell morphology may play roles in response to loading history in MLO-Y4 osteocyte-like cells.

DOI： 10.7717/peerj.10244

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バイオインフォマティクス解析による骨細胞のメカノセンシティブ遺伝子と経路の解析

王紫儀

2020年9月

Screening of key candidate genes and pathways for osteocytes involved in the differential response to different types of mechanical stimulation using a bioinformatics analysis 査読国際誌

Ziyi Wang, Yoshihito Ishihara, Takanori Ishikawa, Mitsuhiro Hoshijima, Naoya Odagaki, Ei Ei Hsu Hlaing, Hiroshi Kamioka

Journal of Bone and Mineral Metabolism 37 ( 4 ) 614 - 626 2019年7月

担当区分：筆頭著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Springer Science and Business Media LLC

Abstract
This study aimed to predict the key genes and pathways that are activated when different types of mechanical loading are applied to osteocytes. mRNA expression datasets (series number of GSE62128 and GSE42874) were obtained from Gene Expression Omnibus database (GEO). High gravity-treated osteocytic MLO-Y4 cell-line samples from GSE62128 (Set1), and fluid flow-treated MLO-Y4 samples from GSE42874 (Set2) were employed. After identifying the differentially expressed genes (DEGs), functional enrichment was performed. The common DEGs between Set1 and Set2 were considered as key DEGs, then a protein–protein interaction (PPI) network was constructed using the minimal nodes from all of the DEGs in Set1 and Set2, which linked most of the key DEGs. Several open source software programs were employed to process and analyze the original data. The bioinformatic results and the biological meaning were validated by in vitro experiments. High gravity and fluid flow induced opposite expression trends in the key DEGs. The hypoxia-related biological process and signaling pathway were the common functional enrichment terms among the DEGs from Set1, Set2 and the PPI network. The expression of almost all the key DEGs (Pdk1, Ccng2, Eno2, Egln1, Higd1a, Slc5a3 and Mxi1) were mechano-sensitive. Eno2 was identified as the hub gene in the PPI network. Eno2 knockdown results in expression changes of some other key DEGs (Pdk1, Mxi1 and Higd1a). Our findings indicated that the hypoxia response might have an important role in the differential responses of osteocytes to the different types of mechanical force.

DOI： 10.1007/s00774-018-0963-7

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その他リンク： http://link.springer.com/article/10.1007/s00774-018-0963-7/fulltext.html

The temporospatial pattern of energy metabolism coordinates the interactions between the bones and other organ systems 招待査読国際誌

Ziyi Wang, Hiroshi Kamioka

Journal of Oral Biosciences 60 ( 1 ) 8 - 14 2018年3月

担当区分：筆頭著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Elsevier {BV}

Abstract
Background: Bones adapt to loads by changing their structure. This biomechanical interaction and the formation/maintenance of bones are orchestrated by three major cell types residing in the bones: osteoblasts, osteocytes, and osteoclasts. Recent findings suggest that, in addition to their biomechanical interactions, bones and other organ systems may also communicate biochemically. Highlight: This brief review will discuss the interaction between the bones and the nervous system, vasculature, muscle, and fat tissues, with an emphasis on the role of the energy metabolism in these interactions. Conclusion: Studies on the connections between bones and other organ systems indicate the possible existence of a temporospatial pattern of energy metabolism through the cellular biorhythm and migration. © 2017 Japanese Association for Oral Biology

DOI： 10.1016/j.job.2017.11.001

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Alternation in the gap-junctional intercellular communication capacity during the maturation of osteocytes in the embryonic chick calvaria 査読国際誌

Ziyi Wang, Naoya Odagaki, Tomoyo Tanaka, Mana Hashimoto, Masahiro Nakamura, Satoru Hayano, Yoshihito Ishihara, Noriaki Kawanabe, Hiroshi Kamioka

Bone 91 20 - 29 2016年10月

担当区分：筆頭著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Elsevier {BV}

Abstract
Introduction: The intercellular network of cell-cell communication among osteocytes is mediated by gap junctions. Gap junctional intercellular communication (GJIC) is thought to play an important role in the integration and synchronization of bone remodeling. To further understand the mechanism of bone development it is important to quantify the difference in the GJIC capacity of young and developmentally mature osteocytes.

Materials and methods: We first established an embryonic chick calvaria growth model to show the growth of the calvaria in embryos at 13 to 21days of age. We then applied a fluorescence recovery after photobleaching (FRAP) technique to compare the difference in the GJIC capacity of young osteocytes with that of developmentally mature osteocytes. Finally, we quantified the dye (Calcein) diffusion from the FRAP data using a mathematic model of simple diffusion which was also used to identify simple diffusion GJIC pattern cells (fitted model) and accelerated diffusion GJIC pattern cells (non-fitted model).

Results: The relationship between the longest medial-lateral length of the calvaria (frontal bone) and the embryonic age fit a logarithmic growth model: length=5.144×ln(day)-11.340. The morphometric data during osteocyte differentiation showed that the cellular body becomes more spindle-shaped and that the cell body volume decreased by approximately 22% with an increase in the length of the processes between the cells. However, there were no significant differences in the cellular body surface area or in the distance between the mass centres of the cells. The dye-displacement rate in young osteocytes was significantly higher than that in developmentally mature osteocytes: dye displacement only occurred in 26.88% of the developmentally mature osteocytes, while it occurred in 64.38% of the young osteocytes. Additionally, in all recovered osteocytes, 36% of the developmentally mature osteocytes comprised non-fitted model cells while 53.19% of the young osteocytes were the non-fitted model, which indicates the active transduction of dye molecules. However, there were no statistically significant differences between the young and developmentally mature osteocytes with regard to the diffusion coefficient, permeability coefficient, or permeance of the osteocyte processes, which were 3.93±3.77 (×10(-8)cm(2)/s), 5.12±4.56 (×10(-5)cm(2)/s) and 2.99±2.47 (×10(-13)cm(2)/s) (mean±SD), respectively.

Conclusions: These experiments comprehensively quantified the GJIC capacity in the embryonic chick calvaria and indicated that the cell-cell communication capacity of the osteocytes in the embryonic chick calvaria was related to their development.

Keywords: Connexins; Fluorescence recovery after photobleaching; Gap-junctional intercellular communication; Mathematic model of simple diffusion; Osteocyte transformation; Osteocytes.

DOI： 10.1016/j.bone.2016.06.016

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BMP-2 generates a functional bone marrow niche by inducing the differentiation of local mesenchymal cells into CAR cells 査読国際誌

2025年3月

Gene expression profiles in human dental pulp stem cells treated short-term with lipopolysaccharides before and after osteoinduction 査読国際誌

Ai Orimoto, Ziyi Wang, Mitsuaki Ono, Chiaki Kitamura, Kentaro Ono

67 ( 1 ) 100603 - 100603 2025年3月

Optimizing β-TCP with E-rhBMP-2-infused fibrin for vertical bone regeneration in a mouse calvarium model 査読国際誌

Kun Zhao, Mitsuaki Ono, Xindi Mu, Ziyi Wang, Shichao Xie, Tomoko Yonezawa, Masahiro Okada, Takuya Matsumoto, Takuo Kuboki, Toshitaka Oohashi

12 2025年1月

Macrophages modulate mesenchymal stem cell function via tumor necrosis factor alpha in tooth extraction model. 査読国際誌

Aung Ye Mun, Kentaro Akiyama, Ziyi Wang, Jiewen Zhang, Wakana Kitagawa, Teisaku Kohno, Ryuji Tagashira, Kei Ishibashi, Naoya Matsunaga, Tingling Zou, Mitsuaki Ono, Takuo Kuboki

JBMR plus 8 ( 8 ) ziae085 2024年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

Mesenchymal stem cells (MSCs) and macrophages collaboratively contribute to bone regeneration after injury. However, detailed mechanisms underlying the interaction between MSCs and inflammatory macrophages (M1) remain unclear. A macrophage-depleted tooth extraction model was generated in 5-wk-old female C57BL/6J mice using clodronate liposome (12.5 mg/kg/mouse, intraperitoneally) or saline injection (control) before maxillary first molar extraction. Mice were sacrificed on days 1, 3, 5, 7, and 10 after tooth extraction (n = 4). Regenerated bone volume evaluation of tooth extraction socket (TES) and histochemical analysis of CD80+M1, CD206+M2 (anti-inflammatory macrophages), PDGFRα+MSC, and TNF-α+ cells were performed. In vitro, isolated MSCs with or without TNF-α stimulation (10 ng/mL, 24 h, n = 3) were bulk RNA-sequenced (RNA-Seq) to identify TNF-α stimulation-specific MSC transcriptomes. Day 7 micro-CT and HE staining revealed significantly lower mean bone volume (clodronate vs control: 0.01 mm3 vs 0.02 mm3, p<.0001) and mean percentage of regenerated bone area per total TES in clodronate group (41.97% vs 54.03%, p<.0001). Clodronate group showed significant reduction in mean number of CD80+, TNF-α+, PDGFRα+, and CD80+TNF-α+ cells on day 5 (306.5 vs 558.8, p<.0001; 280.5 vs 543.8, p<.0001; 365.0 vs 633.0, p<.0001, 29.0 vs 42.5, p<.0001), while these cells recovered significantly on day 7 (493.3 vs 396.0, p=.0004; 479.3 vs 384.5, p=.0008; 593.0 vs 473.0, p=.0010, 41.0 vs 32.5, p=.0003). RNA-Seq analysis showed that 15 genes (|log2FC| > 5.0, log2TPM > 5) after TNF-α stimulation were candidates for regulating MSC's immunomodulatory capacity. In vivo, Clec4e and Gbp6 are involved in inflammation and bone formation. Clec4e, Gbp6, and Cxcl10 knockdown increased osteogenic differentiation of MSCs in vitro. Temporal reduction followed by apparent recovery of TNF-α-producing M1 macrophages and MSCs after temporal macrophage depletion suggests that TNF-α activated MSCs during TES healing. In vitro mimicking the effect of TNF-α on MSCs indicated that there are 15 candidate MSC genes for regulation of immunomodulatory capacity.

DOI： 10.1093/jbmrpl/ziae085

PubMed

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Local E-rhBMP-2/β-TCP Application Rescues Osteocyte Dendritic Integrity and Reduces Microstructural Damage in Alveolar Bone Post-Extraction in MRONJ-like Mouse Model 査読国際誌

Anh Tuan Dang, Mitsuaki Ono, Ziyi Wang, Ikue Tosa, Emilio Satoshi Hara, Akihiro Mikai, Wakana Kitagawa, Tomoko Yonezawa, Takuo Kuboki, Toshitaka Oohashi

International Journal of Molecular Sciences 25 ( 12 ) 6648 - 6648 2024年6月

記述言語：英語掲載種別：研究論文（学術雑誌）

The pathology of medication-related osteonecrosis of the jaw (MRONJ), often associated with antiresorptive therapy, is still not fully understood. Osteocyte networks are known to play a critical role in maintaining bone homeostasis and repair, but the exact condition of these networks in MRONJ is unknown. On the other hand, the local application of E-coli-derived Recombinant Human Bone Morphogenetic Protein 2/β-Tricalcium phosphate (E-rhBMP-2/β-TCP) has been shown to promote bone regeneration and mitigate osteonecrosis in MRONJ-like mouse models, indicating its potential therapeutic application for the treatment of MRONJ. However, the detailed effect of BMP-2 treatment on restoring bone integrity, including its osteocyte network, in an MRONJ condition remains unclear. Therefore, in the present study, by applying a scanning electron microscope (SEM) analysis and a 3D osteocyte network reconstruction workflow on the alveolar bone surrounding the tooth extraction socket of an MRONJ-like mouse model, we examined the effectiveness of BMP-2/β-TCP therapy on the alleviation of MRONJ-related bone necrosis with a particular focus on the osteocyte network and alveolar bone microstructure (microcrack accumulation). The 3D osteocyte dendritic analysis showed a significant decrease in osteocyte dendritic parameters along with a delay in bone remodeling in the MRONJ group compared to the healthy counterpart. The SEM analysis also revealed a notable increase in the number of microcracks in the alveolar bone surface in the MRONJ group compared to the healthy group. In contrast, all of those parameters were restored in the E-rhBMP-2/β-TCP-treated group to levels that were almost similar to those in the healthy group. In summary, our study reveals that MRONJ induces osteocyte network degradation and microcrack accumulation, while application of E-rhBMP-2/β-TCP can restore a compromised osteocyte network and abrogate microcrack accumulation in MRONJ.

DOI： 10.3390/ijms25126648

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Inverse genetics tracing the differentiation pathway of human chondrocytes 査読

H.T. Do, M. Ono, Z. Wang, W. Kitagawa, A.T. Dang, T. Yonezawa, T. Kuboki, T. Oohashi, S. Kubota

Osteoarthritis and Cartilage 2024年6月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Elsevier BV

Abstract
Objective
Mammalian somatic cells can be reprogrammed into induced pluripotent stem cells (iPSCs) via the forced expression of Yamanaka reprogramming factors. However, only a limited population of the cells that pass through a particular pathway can metamorphose into iPSCs, while the others do not. This study aimed to clarify the pathways that chondrocytes follow during the reprogramming process.

Design
The fate of human articular chondrocytes under reprogramming was investigated through a time-coursed single-cell transcriptomic analysis, which we termed an inverse genetic approach. The iPS interference technique was also employed to verify that chondrocytes inversely return to pluripotency following the proper differentiation pathway.

Results
We confirmed that human chondrocytes could be converted into cells with an iPSC phenotype. Moreover, it was clarified that a limited population that underwent the silencing of SOX9, a master gene for chondrogenesis, at a specific point during the proper transcriptome transition pathway, could eventually become iPSCs. Interestingly, the other cells, which failed to be reprogrammed, followed a distinct pathway toward cells with a surface zone chondrocyte phenotype. The critical involvement of cellular communication network factors (CCNs) in this process was indicated. The idea that chondrocytes, when reprogrammed into iPSCs, follow the differentiation pathway backward was supported by the successful iPS interference using SOX9.

Conclusions
This inverse genetic strategy may be useful for seeking candidates for the master genes for the differentiation of various somatic cells. The utility of CCNs in articular cartilage regeneration is also supported.

Keywords
cartilagechondrocytedifferentiationreprogrammingCCN family

DOI： 10.1016/j.joca.2024.06.009

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Exploring the Regulators of Keratinization: Role of BMP-2 in Oral Mucosa 査読国際誌

Xindi Mu, Mitsuaki Ono, Ha Thi Thu Nguyen, Ziyi Wang, Kun Zhao, Taishi Komori, Tomoko Yonezawa, Takuo Kuboki, Toshitaka Oohashi

13 ( 10 ) 807 - 807 2024年5月

Loss-of-function OGFRL1 variants identified in autosomal recessive cherubism families 査読国際共著国際誌

Mizuho Kittaka, Noriyoshi Mizuno, Hiroyuki Morino, Tetsuya Yoshimoto, Tianli Zhu, Sheng Liu, Ziyi Wang, Kotoe Mayahara, Kyohei Iio, Kaori Kondo, Toshio Kondo, Tatsuhide Hayashi, Sarah Coghlan, Yayoi Teno, Andrew Anh Phung Doan, Marcus Levitan, Roy B Choi, Shinji Matsuda, Kazuhisa Ouhara, Jun Wan, Annelise M Cassidy, Stephane Pelletier, Sheela Nampoothiri, Andoni J Urtizbera, Alexander G Robling, Mitsuaki Ono, Hideshi Kawakami, Ernst J Reichenberger, Yasuyoshi Ueki

JBMR Plus 8 ( 6 ) ziae050 2024年4月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Oxford University Press (OUP)

Cherubism (OMIM 118400) is a rare craniofacial disorder in children characterized by destructive jawbone expansion due to the growth of inflammatory fibrous lesions. Our previous studies have shown that gain-of-function mutations in SH3 domain-binding protein 2 (SH3BP2) are responsible for cherubism and that a knock-in mouse model for cherubism recapitulates the features of cherubism, such as increased osteoclast formation and jawbone destruction. To date, SH3BP2 is the only gene identified to be responsible for cherubism. Since not all patients clinically diagnosed with cherubism had mutations in SH3BP2, we hypothesized that there may be novel cherubism genes and that these genes may play a role in jawbone homeostasis. Here, using whole exome sequencing, we identified homozygous loss-of-function variants in the opioid growth factor receptor like 1 (OGFRL1) gene in two independent autosomal recessive cherubism families from Syria and India. The newly identified pathogenic homozygous variants were not reported in any variant databases, suggesting that OGFRL1 is a novel gene responsible for cherubism. Single cell analysis of mouse jawbone tissue revealed that Ogfrl1 is highly expressed in myeloid lineage cells. We generated OGFRL1 knockout mice and mice carrying the Syrian frameshift mutation to understand the in vivo role of OGFRL1. However, neither mouse model recapitulated human cherubism or the phenotypes exhibited by SH3BP2 cherubism mice under physiological and periodontitis conditions. Unlike bone marrow-derived M-CSF-dependent macrophages (BMMs) carrying the SH3BP2 cherubism mutation, BMMs lacking OGFRL1 or carrying the Syrian mutation showed no difference in TNF-ɑ mRNA induction by LPS or TNF-ɑ compared to wild-type BMMs. Osteoclast formation induced by receptor activator of NF-κB ligand (RANKL) was also comparable. These results suggest that the loss-of-function effects of OGFRL1 in humans differ from those in mice and highlight the fact that mice are not always an ideal model for studying rare craniofacial bone disorders.

DOI： 10.1093/jbmrpl/ziae050

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Antitumor activity of α‐pinene in T‐cell tumors 査読

Masaya Abe, Noboru Asada, Maiko Kimura, Chie Fukui, Daisuke Yamada, Ziyi Wang, Masayuki Miyake, Takeshi Takarada, Mitsuaki Ono, Michinori Aoe, Wataru Kitamura, Masayuki Matsuda, Takashi Moriyama, Akifumi Matsumura, Yoshinobu Maeda

Cancer Science 2024年1月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Wiley

Abstract

T‐cell acute leukemia and lymphoma have a poor prognosis. Although new therapeutic agents have been developed, their therapeutic effects are suboptimal. α‐Pinene, a monoterpene compound, has an antitumor effect on solid tumors; however, few comprehensive investigations have been conducted on its impact on hematologic malignancies. This report provides a comprehensive analysis of the potential benefits of using α‐pinene as an antitumor agent for the treatment of T‐cell tumors. We found that α‐pinene inhibited the proliferation of hematologic malignancies, especially in T‐cell tumor cell lines EL‐4 and Molt‐4, induced mitochondrial dysfunction and reactive oxygen species accumulation, and inhibited NF‐κB p65 translocation into the nucleus, leading to robust apoptosis in EL‐4 cells. Collectively, these findings suggest that α‐pinene has potential as a therapeutic agent for T‐cell malignancies, and further investigation is warranted.

DOI： 10.1111/cas.16086

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Ruxolitinib altered IFN-β induced necroptosis of human dental pulp stem cells during osteoblast differentiation 査読

Atsuko Tanaka, Satoru Hayano, Masayo Nagata, Takahiro Kosami, Ziyi Wang, Hiroshi Kamioka

Archives of Oral Biology 155 105797 2023年11月

Lgr5-expressing secretory cells form a Wnt inhibitory niche in cartilage critical for chondrocyte identity 査読

Angela Ruscitto, Peng Chen, Ikue Tosa, Ziyi Wang, Gan Zhou, Ingrid Safina, Ran Wei, Mallory M. Morel, Alia Koch, Michael Forman, Gwendolyn Reeve, Michael K. Lecholop, Marshall Wilson, Daniel Bonthius, Mo Chen, Mitsuaki Ono, Timothy C. Wang, Hai Yao, Mildred Embree

Cell Stem Cell 30 ( 9 ) 1179 - 1198 2023年9月

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