Cell Proliferation最新文献

{"title":"Soluble Sema4D From γδ T Cells Exerts Osteoblast Inhibition via Plexin-B/mTOR Signalling Contributing to Pathogenesis of Bisphosphonate-Related Osteonecrosis of the Jaws.","authors":"Lingling Ou, Shijia Qiao, Zhuoyi Liao, Xiner Tan, Hui Huang, Zhiyan Zhou, Ruhui Luo, Weijun Zeng, Yan Yang, Zhongxuan Zhang, Jingchen Chen, Shengli Wang, Yiqin Jiang, Jianlei Hao, Yuqin Shen, Longquan Shao","doi":"10.1111/cpr.70114","DOIUrl":"https://doi.org/10.1111/cpr.70114","url":null,"abstract":"<p><p>Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a severe complication in patients undergoing long-term bisphosphonate therapy, while our knowledge on the pathogenesis of BRONJ is far from sufficient. Gamma delta (γδ) T cells predominantly distribute in mucosal tissues and play an important role in both immune modulation and bone metabolism; however, the mechanism of γδ T cells in the pathogenesis of BRONJ has not been elucidated. Here, we induced BRONJ-like lesions in wild-type (WT) and T-cell receptor delta-deficient (TCRδ^-/-) mice via intraperitoneal zoledronate injection. Our findings revealed that γδ T cells infiltrating BRONJ lesions suppressed osteoblast differentiation, whereas γδ T cell depletion in TCRδ^-/- mice restored osteogenic function and significantly reduced BRONJ lesion incidence. Mechanistically, we identified matrix metalloproteinase 3 (MMP3) secreted by activated γδ T cells as a critical enzyme cleaving membrane-bound Sema4D (mSema4D) into soluble Sema4D (sSema4D). This cleavage product bound to Plexin-B1/2 receptors on osteoblasts, activating the mTOR signalling pathway to inhibit osteogenic differentiation (ALP/Runx2 downregulation). To promote the repair of BRONJ lesions, we engineered a dual-functional composite hydrogel (Gel-BG@ab) combining PLGA-PEG-PLGA with mesoporous bioactive glass (BG) and anti-Sema4D antibodies. This composite hydrogel achieved sustained antibody release, effectively neutralising sSema4D, restoring osteoblast activity and reducing the formation of BRONJ-like lesions in vivo. This study provides evidence of MMP3-Sema4D-Plexin-B1/2/mTOR crosstalk in BRONJ and introduces a targeted biomaterial strategy to disrupt pathogenic feedback loops. The Gel-BG@ab is the integration of immunomodulation and regenerative medicine, providing both theoretical and technical insights for the immune-material combination therapy of BRONJ.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e70114"},"PeriodicalIF":5.6,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144999712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting ARPC1B⁺ Cancer Stem Cells to Sensitise Pancreatic Cancer to Gemcitabine Treatment.","authors":"Yang Wu, Jianpeng Zhang, Weixiong Zhu, Xinrui Zhu, Yi Liu, Xin Wang, Tianyu Zhao, Chun Zhang, Zili Zhang, Wenjie Shi, Run Shi, Zhaokai Zhou, Shaohui Xu","doi":"10.1111/cpr.70125","DOIUrl":"https://doi.org/10.1111/cpr.70125","url":null,"abstract":"<p><p>ARPC1B⁺ cancer stem cells (CSCs) in pancreatic cancer are identified as a subpopulation resistant to gemcitabine. In our study, drug repositioning, molecular docking, and surface plasmon resonance (SPR) technique jointly revealed that CK-636 can directly target ARPC1B protein with high affinity. In vitro cytotoxicity, ex vivo organoid cultures, in vivo xenograft and orthotopic gemcitabine-resistant pancreatic cancer model demonstrated that combination therapy of gemcitabine plus CK-636 showed a superior anti-tumor effect compared with gemcitabine monotherapy. Our study demonstrated that CK-636 can act as a rational adjuvant to overcome gemcitabine resistance in pancreatic cancer therapy.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e70125"},"PeriodicalIF":5.6,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Impact of Maternal Gut Dysbiosis on Embryo/Fetus Development.","authors":"Nairui Fan, Yao Shen, Xuesong Yang, Shuxia Ma, Guang Wang","doi":"10.1111/cpr.70124","DOIUrl":"https://doi.org/10.1111/cpr.70124","url":null,"abstract":"","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e70124"},"PeriodicalIF":5.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144944616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to \"Ski Promotes Proliferation and Inhibits Apoptosis in Fibroblasts Under High-Glucose Conditions via the FoxO1 Pathway\".","authors":"","doi":"10.1111/cpr.70116","DOIUrl":"https://doi.org/10.1111/cpr.70116","url":null,"abstract":"","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e70116"},"PeriodicalIF":5.6,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144944643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of NAFLD-Specific Human Liver Organoid Models on a Microengineered Array Chip for Semaglutide Efficacy Evaluation.","authors":"Xiao-Yan You, Xiang-Yang Li, Hui Wang, Guo-Ping Zhao","doi":"10.1111/cpr.70118","DOIUrl":"https://doi.org/10.1111/cpr.70118","url":null,"abstract":"<p><p>Progressive non-alcoholic fatty liver disease (NAFLD) may culminate in severe complications, including fibrosis, cirrhosis and hepatocellular carcinoma, yet therapeutic breakthroughs remain elusive, necessitating novel pharmacological strategies. Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist clinically approved for type 2 diabetes and obesity management, has demonstrated pleiotropic effects in preclinical NAFLD models. In this study, we investigated semaglutide's therapeutic efficacy and mechanisms in a human liver organoids (hLOs) model of NAFLD. Utilising microengineered array chips, human induced pluripotent stem cells (hiPSCs) were differentiated into hLOs with functional hepatic properties. NAFLD pathology was induced via free fatty acid (FFA) exposure, recapitulating disease hallmarks such as steatosis, inflammatory cytokine elevation and fibrogenic activation. Semaglutide treatment at 50 nM significantly attenuated lipid deposition caused by FFAs and reduced triglyceride levels by 8-fold and cholesterol levels by 1.8-fold. It also inhibited the expression of pro-inflammatory markers (IL-6, IL-8, TNF-α) by about 1.5-2 fold and increased the level of lipolytic genes by about 45%. These findings elucidate the therapeutic potential of semaglutide in attenuating key NAFLD-associated pathologies and establish a robust in vitro platform for preclinical drug evaluation. The study provides critical insights into targeted NAFLD interventions and supports the translation of GLP-1-based therapies into clinical practice, addressing an unmet need in hepatology.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e70118"},"PeriodicalIF":5.6,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144944595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanical Force Promotes Mitochondrial Transfer From Macrophages to BMSCs to Enhance Bone Formation.","authors":"Yingyi Li, Ziwei Yan, Yueming Dai, Hanjia Cai, Yue Chen, Yuyi Chen, Ruofan Jin, Wen Sun, Hua Wang","doi":"10.1111/cpr.70121","DOIUrl":"https://doi.org/10.1111/cpr.70121","url":null,"abstract":"<p><p>Macrophages and bone marrow mesenchymal stem cells (BMSCs) share a close relationship within the osteoimmune microenvironment. During mechanically induced bone formation, macrophages respond to stimuli and regulate this microenvironment, influencing BMSCs' proliferation and differentiation. However, the underlying mechanisms remain incompletely understood. In our study, we employed a cellular tension system and found that mechanical tension altered mitochondrial dynamics in macrophages, leading to increased mitochondrial fission. Using a macrophage-BMSC direct co-culture system, we demonstrated that macrophages transferred mitochondria to BMSCs, a process enhanced by tension. This enhancement was associated with Drp1-mediated mitochondrial fission, as Drp1 knockdown in macrophages abolished the effect. Additionally, using in vitro co-culture and in vivo tibial injection models, we found that mitochondria-rich extracellular vesicles (Mito-EVs) secreted by mechanically stretched macrophages promoted BMSCs' osteogenesis and enhanced bone formation via the CD200 receptor (CD200R)-CD200 interaction. Our findings reveal a pivotal role for mitochondrial transfer in promoting osteogenesis during mechanotransduction, highlighting a novel mechanism of intercellular communication in bone biology.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e70121"},"PeriodicalIF":5.6,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144944646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Influenza A Virus (H1N1) Infection Induces Ferroptosis to Promote Developmental Injury in Fetal Tissues.","authors":"Yuxi Jiang, Yao Shen, Qiongyin Zhang, Zi Liu, Yuzhen Liu, Jiaojiao Peng, Xuesong Yang, Feng Gao, Xiang-Hong Ou, Qing-Yuan Sun, Qiao Zhang, Guang Wang","doi":"10.1111/cpr.70117","DOIUrl":"https://doi.org/10.1111/cpr.70117","url":null,"abstract":"<p><p>H1N1, a globally pervasive subtype of influenza A virus (IAV), poses an ongoing threat to human health and occasionally leads to multi-organ dysfunction in severe cases. Evidence confirms that the H1N1 virus is enabled to penetrate the placental barrier; however, the underlying mechanisms by which maternal infection contributes to detrimental fetal outcomes remain elusive. In this study, a systematic literature review and meta-analysis demonstrated a strong association between maternal H1N1 infection during pregnancy and adverse fetal outcomes. Using a chicken embryo model, we found that the H1N1 virus specifically targets the developing liver and lung tissues, activates immune and stromal cells, and induces localised inflammatory responses, thereby triggering excessive oxidative stress. The resulting imbalance in oxidative stress disrupts antioxidant defence systems and promotes ferroptosis in parenchymal cells. Persistent ferroptosis subsequently initiates tissue repair processes, activates fibroblasts, and leads to aberrant extracellular matrix deposition, ultimately contributing to early fibrosis in the liver and lung tissues. Collectively, this study elucidates the molecular mechanisms by which H1N1 selectively infects fetal liver and lung, inducing ferroptosis-mediated parenchymal cell death and tissue fibrosis, thereby impairing fetal development. These findings provide novel theoretical insights for the clinical management and prevention of H1N1-associated maternal-fetal infections and adverse pregnancy outcomes.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e70117"},"PeriodicalIF":5.6,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144944651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Primary Cilia Orchestrate Cardiac Pathogenesis: A Central Nexus of Remodeling, Signaling, and Repair","authors":"Yang Yang,&nbsp;Kaidi Ren,&nbsp;Xingjuan Shi,&nbsp;Yi Luan","doi":"10.1111/cpr.70113","DOIUrl":"10.1111/cpr.70113","url":null,"abstract":"<p>Roles of primary cilia and the signals they transmit in the development of myocardial fibrogenesis, cardiac hypertrophy, and atrial fibrillation. Left, Fibroblasts can differentiate into myofibroblasts in response to TGF-β1. TGF-β1 stimulation via both paracrine action in the heart and exogenous action on primary cultured fibroblasts activated the phosphorylation of SMAD3 and the transcription of the fibronectin and collagen type I and III genes. Middle, Vesicles derived from cilia are secreted at an accelerated rate under fluid shear stress. Blockage of ciliary protein, which is required for cELV generation with shRNA, led to blunted cELV secretion and left ventricular hypertrophy. Right, under pathological conditions such as atrial fibrillation (AF), fibroblasts exhibit increased proliferation and differentiation into α-smooth muscle Actin (αSMA)-expressing myofibroblasts. This disrupts ECM dynamics, ultimately leading to interstitial fibrosis within the atria. AF patients presented increased HDAC6 activity and reduced levels of acetylated α-tubulin in left atrial tissues. HDAC6 activity is activated by the interaction of aurora kinase A (AURKA), and neural precursor cells express developmentally downregulated protein 9 (NEDD9) via phosphorylation. LiCl prompts the reversion of αSMA-positive myofibroblasts into αSMA-negative fibroblasts.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":"58 10","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cpr.70113","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144944620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ageing-Dependent Thyroid Hormone Receptor α Reduction Activates IP3R1-Meditated Ca²⁺ Transfer in MAM and Exacerbates Skeletal Muscle Atrophy in Mice.","authors":"Runqing Shi, Yusheng Zhang, Gong Chen, Jiru Zhang, Jing Liu, Hao Zhu, Minne Sun, Yu Duan","doi":"10.1111/cpr.70120","DOIUrl":"https://doi.org/10.1111/cpr.70120","url":null,"abstract":"<p><p>Sarcopenia profoundly impacts the quality of life and longevity in elderly populations. Notably, alterations in thyroid hormone (TH) levels during ageing are intricately linked to the development of sarcopenia. In skeletal muscle, the primary action of TH is mediated through the thyroid hormone receptor alpha (TRα). Emerging evidence suggests that decreased TRα expression may precipitate mitochondrial dysfunction in ageing skeletal muscle tissues. Yet, the precise mechanisms and the potential causative role of TRα deficiency in sarcopenia are not fully understood. This study suggests that TRα may regulate mitochondrial calcium (Ca²⁺) transport across membranes by targeting the inositol 1,4,5-trisphosphate receptor 1 (IP3R1), as evidenced by ChIP-seq and RNA-seq analyses. Experiments using naturally aged mice, skeletal muscle-specific TRα knockout (SKT) mice, and C2C12 myoblasts were conducted to investigate this process further. Findings include increased IP3R1, mitochondria-associated endoplasmic reticulum membranes (MAM), and mitochondrial Ca²⁺ in aged skeletal muscle. Additionally, SKT mice exhibited smaller muscle fibres, increased IP3R1 and MAM, and mitochondrial dysfunction. ChIP-qPCR and TRα manipulation in C2C12 cells showed that TRα negatively regulates IP3R1 transcription. Moreover, TRα knockdown cells exhibited increased Ca²⁺ transfer in MAM and mitochondrial dysfunction, which was ameliorated by the IP3R1 inhibitor 2-aminoethoxydiphenyl borate. Reintroduction of TRα improved IP3R1-mediated mitochondrial Ca²⁺ overload in aged cells. Our findings uncover a novel mechanism by which TRα deficiency induces mitochondrial Ca²⁺ overload through IP3R1-mediated Ca²⁺ transfer in MAM, exacerbating skeletal muscle atrophy during ageing. The TRα/IP3R1 pathway in MAM Ca²⁺ transfer presents a potential therapeutic target for sarcopenia.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e70120"},"PeriodicalIF":5.6,"publicationDate":"2025-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144944633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to “An Aggregation of Human Embryonic and Trophoblast Stem Cells Reveals the Role of Trophectoderm on Epiblast Differentiation”","authors":"","doi":"10.1111/cpr.70115","DOIUrl":"10.1111/cpr.70115","url":null,"abstract":"<p>X. Wu, W. Zhao, H. Wu, Q. Zhang, Y. Wang, K. Yu, J. Zhai, F. Mo, M. Wang, S. Li, X. Zhu, X. Liang, B. Hu, G. H. Liu, J. Wu, H. Wang, F. Guo, and L. Yu, “An Aggregation of Human Embryonic and Trophoblast Stem Cells Reveals the Role of Trophectoderm on Epiblast Differentiation,” <i>Cell Proliferation</i> 56, no. 5 (2023 May): e13492, https://doi.org/10.1111/cpr.13492.</p><p>In the originally published version of this article, <b>Figure 4E</b> contained an unintended duplication error. Specifically, the left and right panels were mistakenly presented as identical due to a manual error during figure reformatting. This occurred while the figure was being adjusted for higher resolution.</p><p>We apologize for this error.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":"58 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cpr.70115","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144834252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}