{"title":"Changes in the immunohistochemical expression of nephrin protein in renal corpuscle of rats in response to sleep disturbance","authors":"Zahraa Aboud Mohsin, Huda R. Kamoona","doi":"10.1007/s10735-025-10372-z","DOIUrl":"10.1007/s10735-025-10372-z","url":null,"abstract":"<div><p>Sleep is an essential health requirement; human body needs sufficient amount and quality of sleep to ensure its health. Sleep disturbance led to deterioration in renal functions. This study aimed to asses effect of sleep disturbance on nephrin protein in renal corpuscle. A sample of thirty adult male albino rats, subjected to sleep disturbance by light, divided into three groups; control group with normal sleep rhythm of 12–12 h dark- light phases, group A: subjected to interruption of sleep by light at three intervals, group B: rats were exposed to a reduction in sleep time by continuous light stimulation for 7 h. Animals were sacrificed by euthanasia, their kidneys were dissected and prepared for paraffin, sections stained for Nephrin protein, and the immunohistochemical intensity was quantified by Aperio Image Scope analysis software. This study showed variations in the effect of sleep disturbance patterns by light exposure on nephrin protein expression in renal corpuscles; in the control group a strong patchy distribution of Nephrine in the peripheral region of the glomerulus, group A showed a significant reduction compared to the control group, and group B a weak expression of nephrin protein in the glomerulus, with significant changes between group B and group A, but no significant changes between group B and control. These changes reflect that sleep disturbance affects the structural integrity of the slit diaphragm and nephrin protein expression, which is considered a novel protein for the slit diaphragm structural integrity, and a sign of podocyte injury.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 2","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143423105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Sirt1/FOXO signal pathway involves in regulating osteomyelitis progression via modulating mitochondrial dysfunctions and osteogenic differentiation","authors":"Runyao Zhang, Nannan Kou, Feifei Liu, Huan Tong, Shaobo Li, Lirong Ren","doi":"10.1007/s10735-025-10370-1","DOIUrl":"10.1007/s10735-025-10370-1","url":null,"abstract":"<div><p>The Sirtuin-1 (Sirt1) gene has been reported to be closely associated with the progression of multiple diseases, but its role in regulating osteomyelitis (OM) pathogenesis has not been explored. The murine long bone-derived osteocyte-like MLO-Y4 cells and osteoblast-like MC3T3-E1 cells were exposed to Staphylococcal protein A (SpA) treatment to establish the in vitro OM models. The expression levels of Osteoblast-specific genes (OCN, OPN and RUNX2), osteoclastic genes (CTSK, MMP9 and ACP5) and the FOXO pathway-related proteins (FOXO1, p-FOXO1, FOXO3 and p-FOXO3) were detected by performing Real-Time qPCR and Western Blot analysis. Osteoblastic differentiation of the cells were evaluated by using the alizarin red S staining assay and TRAP staining assay, and membrane potential and superoxide production were measured to evaluate the mitochondrial functions of the cells. SpA treatment significantly suppressed osteogenic differentiation and induced mitochondrial dysfunction in MLO-Y4 and MC3T3-E1 cells, and promoting osteoclastogenesis in RAW264.7 cells, suggesting that the in vitro OM models were successfully established. Of note, SpA decreased the expression levels of Sirt1 in the OM cells, and SpA-induced detrimental effects on the OM cells were all reversed by overexpressing Sirt1. Mechanistically, Sirt1-overexpression increased the levels of phosphorylated FOXO-related proteins (p-FOXO1 and p-FOXO3) to activate the FOXO signal pathway and ameliorated OM progression in SpA-treated cells. Collectively, it was revealed in the present study that overexpression of Sirt1 activated the FOXO signal pathway to ameliorate SpA-induced detrimental effects in the OM cells, and Sirt1 could be potentially used as therapeutic agent for OM in clinic.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 2","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143396594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Melanomacrophage centers in Gymnotus carapo as environmental bioindicators: histological and morphometric analysis in kidney, liver, and spleen","authors":"Sabrina Méndez Galarza, Gabriela Olea, Eduen Gross, Tania Blanco Cohene , Carolina Flores Quintana","doi":"10.1007/s10735-025-10365-y","DOIUrl":"10.1007/s10735-025-10365-y","url":null,"abstract":"<div><p>This study analyzes the morphology of melanomacrophage centers (MMCs) in the kidney, liver, and spleen of <i>Gymnotus carapo</i> across two different environmental settings with varying degrees of anthropogenic impact, aiming to link habitat conditions to fish health and validate MMCs as bioindicators for environmental monitoring. A total of 28 specimens, captured and humanely sacrificed under anesthesia, were processed using conventional histological techniques. Morphometric measurements were recorded, and tissue samples were examined on an Olympus BX 41 microscope, selecting 10 random 10x fields per organ to count MMCs. Macroscopic and histological examination of the liver, kidney, and spleen highlighted MMCs distribution patterns and notable differences across sex and age groups. Adult and juvenile males showed major MMCs counts in the kidney and spleen compared to females, while liver samples from both sexes contained only pigmented cells without significant MMCs formation. Differences in MMCs quantity and structure were also observed between environments: natural habitats displayed lower MMCs counts in both sexes compared to samples from locations with higher anthropogenic impact, where MMCs frequency and pigmentation intensity were notably elevated. These findings suggest that MMCs variations in <i>G. carapo</i> may reflect environmental conditions and stressors, supporting the potential application of MMCs as health indicators for aquatic organisms and ecosystem monitoring. This work provides comprehensive morphometric and histological data on MMCs distribution in <i>G. carapo</i>, emphasizing its potential as a bioindicator species, particularly valuable in regions with varying pollution levels.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 2","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143379826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Panpan Yang, He Wang, Lingxiao Meng, Yuying Kou, Jie Bu, Minqi Li
{"title":"Methylase METTL3 regulates oxidative stress-induced osteoblast apoptosis through Wnt/β-catenin signaling pathway","authors":"Panpan Yang, He Wang, Lingxiao Meng, Yuying Kou, Jie Bu, Minqi Li","doi":"10.1007/s10735-025-10358-x","DOIUrl":"10.1007/s10735-025-10358-x","url":null,"abstract":"<div><p>The latest research shows that the imbalance of reactive oxygen species (ROS) leads to oxidative stress-induced osteoblast apoptosis, which is an important factor in the development of osteoporosis. Methyltransferase like 3 (METTL3) is the most widely known methyltransferase, which has a marked effect on the cells of oxidative stress reaction. However, the precise mechanism through which METTL3 mediates oxidative stress-induced osteoblast apoptosis remains uncleared. An ovariectomized (OVX) rat model was established and histochemical staining were used to evaluate bone mass and the expression of METTL3. The oxidative stress state of bone tissue and the expression of METTL3 were detected by RT-PCR. The reactive oxygen species (ROS) levels were detected by DCFH-DA staining. Cell death and apoptosis were detected by CCK8, Hoechst PI double dyeing and TUNEL staining. The mitochondrial membrane potential was detected by JC-1 fluorescent staining. The expression of N6-methyladenosine, the protein levels of cell apoptosis and Wnt/β-catenin signal were detected by RT-PCR and western blot. We demonstrated that METTL3 was highly expressed in OVX-induced osteoporosis, and it inhibited oxidative stress-induced apoptosis of MC3T3-E1 cells by downregulating the ROS-mediated activation of the Wnt/β-catenin signaling pathway in osteoblasts. In addition, under oxidative stress, ROS accumulation further inhibited METTL3 expression and activated the Wnt/β-catenin signaling pathway, which ultimately led to apoptosis of MC3T3-E1 cells. This study investigated the important role of METTL3 in oxidative stress-induced osteoblast apoptosis. It may be a new therapeutic target for osteoporosis from the perspective of oxidative stress.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 2","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143379825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marcelo Henrique Garcia, Thiago José Dionísio, Tânia Mary Cestari, Viviane Aparecida Parisi, Elza Araújo Torres, Carlos Ferreira Santos
{"title":"The role of AT-1 antagonist on wound healing in rats with hypertension and diabetes","authors":"Marcelo Henrique Garcia, Thiago José Dionísio, Tânia Mary Cestari, Viviane Aparecida Parisi, Elza Araújo Torres, Carlos Ferreira Santos","doi":"10.1007/s10735-025-10357-y","DOIUrl":"10.1007/s10735-025-10357-y","url":null,"abstract":"<div><p>Wound healing is a complex process involving molecular and structural interactions. Transforming growth factor β (TGF-β), the renin-angiotensin system (RAS), and other important mediators play a central role on wound healing process. This study examined the dynamics of healing in healthy, hypertensive, and diabetic rats treated with or without Losartan, focusing on healing rate, scar characteristics, and molecular modulation. Macroscopic and microscopic analyses revealed delayed healing and reduced collagen deposition in diabetic and hypertensive rats compared with normoglycemic controls. Losartan affected healing by regulating TGF-β expression and collagen organization. In the groups of hypertensive and diabetic rats treated with losartan, healing aesthetics improved by less collagen deposition and consequently minor chances to fibrosis development, probably due to lower TGFβ and SMADs expression. Diabetic rats showed reduced skin and collagen fiber thickness, whereas hypertensive rats showed better healing under Losartan treatment (LT). These results demonstrate the complex interactions between LT, diabetes and hypertension on important fibrotic and inflammatory pathways. Although LT successfully reduces TGF-β expression and classical SMAD signaling in hypertensive settings, its minor effect in diabetes conditions indicate the necessity of supplemental treatments that target mechanisms unique to hyperglycemia, such as glycation end products or oxidative stress inhibitors. To improve treatment outcomes for individuals with diabetes and hypertension comorbidities, future studies should investigate the combination of multi-pathway modulators.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 2","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143361853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Identification and study of mood-related biomarkers and potential molecular mechanisms in type 2 diabetes mellitus","authors":"Menglong Wang, Tongrui Wang, Yang Liu, Lurong Zhou, Yuanping Yin, Feng Gu","doi":"10.1007/s10735-025-10353-2","DOIUrl":"10.1007/s10735-025-10353-2","url":null,"abstract":"<div><p>A significant correlation between type 2 diabetes mellitus (T2DM) and mood has been reported. However, the specific mechanism of mood’s role in T2DM is unclear. This study aims to discover mood-related biomarkers in T2DM and further elucidate their underlying molecular mechanisms. The GSE81965 and GSE55650 datasets were sourced from public databases, and mood-related genes (MRGs) were retrieved from previous literature. Initially, differentially expressed MRGs (DE-MRGs) were obtained by combining differential expression analysis and weighted gene co-expression network analysis (WGCNA). Subsequently, the DE-MRGs were incorporated into the LASSO and SVM to identify diagnostic biomarkers for T2DM. Four machine learning methods were utilized to construct the diagnostic models in T2DM, and the model with the optimal algorithm was screened. Further, based on biomarkers, functional enrichment, immune infiltration, and regulatory network analyses were conducted to excavate deeper into the pathogenesis of T2DM. In vivo experiments were used to validate the expression of the biomarkers. A total of 23 DE-MRGs were identified by overlapping 723 DEGs and 64 key modules, and there were strong positive correlations between these DE-MRGs. Afterward, KCTD16, SLC8A1, RAB11FIP1, and RASGEF1B were identified as biomarkers associated with mood in T2DM, and they had favorable diagnostic performance. Meanwhile, the RF diagnostic model constructed based on biomarkers was performed optimally and had high diagnostic accuracy for T2DM patients. Animal experiments indicated that expression levels of SLC8A1, RAB11FIP1, and RASGEF1B in T2DM were consistent with the microarray results. In conclusion, KCTD16, SLC8A1, RAB11FIP1, and RASGEF1B were identified as biomarkers related to mood in T2DM.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 2","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143361914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Honghao Chen, Mi Yan, Xiaoping Cai, Yongqin Zheng, Guoyuan Li, Kai Gao, Wei Wang, Jianwei Huang, Yingyi Xu, Zhuorong Zhang
{"title":"Identification of IFI27 involvement in the progression of neuroblastoma through bioinformatics analysis and experimental assays","authors":"Honghao Chen, Mi Yan, Xiaoping Cai, Yongqin Zheng, Guoyuan Li, Kai Gao, Wei Wang, Jianwei Huang, Yingyi Xu, Zhuorong Zhang","doi":"10.1007/s10735-024-10346-7","DOIUrl":"10.1007/s10735-024-10346-7","url":null,"abstract":"<div><p>Neuroblastoma (NB) is a prevalent extracranial malignant neuroendocrine tumor in children, originating from the sympathetic nervous system. This study aims to investigate new therapeutic targets for NB. The differentially expressed genes were screened by analyzing the GSE35133 and GSE90689 datasets. Hub genes were identified by constructing a protein–protein interaction network. The diagnostic value of the hub genes was assessed through the analysis of receiver operating characteristic (ROC) curves and the expression, prognosis, and immune infiltration of IFI27 in pan-cancer were analyzed on the online website Sangerbox. The hub gene expression levels were validated by performing real-time reverse transcriptase-polymerase chain reaction. The functions of IFI27 in NB were investigated by Cell Counting Kit-8, 5-ethynyl-2'-deoxyuridine, wound healing, and Transwell assays. Six candidate genes (IFI27, TNFSF10, IFI44, DDX58, HIST1H1C, and HIST1H1E) were identified as potential diagnostic biomarkers for NB. The expression levels of IFI27, TNFSF10, IFI44, and DDX58 were significantly decreased, while HIST1H1C and HIST1H1E were elevated. Notably, IFI27 displayed correlations with prognosis and immune infiltration in multiple tumors. In vitro, functional assays demonstrated that the knockdown of IFI27 promoted the proliferation, migration, and invasion of U251 cells. Conversely, in SK-N-AS cells, IFI27 overexpression inhibited cell proliferation, migration, and invasion. IFI27 was lowly expressed in NB and participated in the progression of NB, which provides a new insight into the pathogenic mechanism and novel therapeutic strategy for NB.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 2","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143361909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Amira I. Shrief, Dina S. Elshenawy, Ahmed E. Elsukary, Sally A. Elekhtiar, Ola A. Yahia
{"title":"Behavioral and histological study on the neuroprotective effect of thymoquinone on the cerebellum in AlCl3-induced neurotoxicity in rats through modulation of oxidative stress, apoptosis, and autophagy","authors":"Amira I. Shrief, Dina S. Elshenawy, Ahmed E. Elsukary, Sally A. Elekhtiar, Ola A. Yahia","doi":"10.1007/s10735-025-10361-2","DOIUrl":"10.1007/s10735-025-10361-2","url":null,"abstract":"<div><p>Alzheimer disease (AD) is a neurodegenerative condition. Thymoquinone (TQ) is a natural compound that possesses beneficial biological effects on the brain. The present study evaluates the protective impact of TQ on the cerebellum in rats with AlCl3-induced Alzheimer's disease. Four groups were utilized. Control: 20 rats that were subdivided into two subgroups. Ia: received distilled water for 4 weeks. Ib: received corn oil via oral gavage (1 ml/kg daily) for 4 weeks. TQ group: 10 rats received TQ in corn oil via oral gavage (20 mg/kg daily) for 4 weeks. AD group:10 rats received AlCl3 in distilled water via oral gavage (300 mg/kg daily) for 4 weeks. AD & TQ group: 10 rats received both AlCl3 & TQ for 4 weeks. The grip period in the rotarod test decreased, escape latency in first three days and the entry latency period to the quadrant with the removed escape platform in the Morris water maze test increased in AD group, but when TQ was administered concurrently, there was a noteworthy improvement. Meanwhile, when compared to AD group, the addition of TQ showed a significant decrease (<i>P</i> < 0.05) in levels of malondialdehyde (MDA) and nitric oxide (NO), associated with a significant increase (<i>P</i> < 0.05) in reduced glutathione (GSH) level. Furthermore, AD & TQ group exhibited substantial preservation of the cerebellum's histological structure, the Purkinje cells number and transverse diameter showed a high significant increase (<i>P</i> < 0.001) and a significant increase (<i>P</i> < 0.05), respectively in comparison to the AD group. Using TQ showed improvement in behavioral tests, biochemical and histological findings. Thus, TQ might have therapeutic effects on Alzheimer’s disease.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 2","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"E2F1-Dependent CDCA5 overexpression drives cervical cancer progression and correlates with poor prognosis","authors":"Youhui Wang, Wuguang Zhang, Min Peng","doi":"10.1007/s10735-025-10356-z","DOIUrl":"10.1007/s10735-025-10356-z","url":null,"abstract":"<div><p>Cervical cancer (CC) remains a leading cause of cancer-related mortality in women worldwide, highlighting the urgent need for novel therapeutic strategies. This study investigates the molecular mechanisms and clinical significance of Cell Division Cycle Associated 5 (CDCA5) in cervical cancer progression. We performed comprehensive analyses of CDCA5 expression in cervical cancer and normal tissues, correlating expression levels with clinicopathological features and patient outcomes. Functional studies using CC cell lines (SiHa, HeLa, and CaSki) examined the effects of CDCA5 manipulation on tumor cell behavior. We identified E2F1 as a key transcriptional regulator of CDCA5 and validated our findings using in vivo xenograft models. CDCA5 was significantly upregulated in CC tissues and correlated with advanced disease stages and poor survival outcomes. Mechanistically, CDCA5 depletion in SiHa and HeLa cells suppressed proliferation, migration, and invasion, while its overexpression in CaSki cells enhanced these malignant properties. We identified E2F1 as a transcriptional activator of CDCA5. Importantly, CDCA5 knockdown significantly inhibited tumor growth in nude mouse models. Our findings establish CDCA5 as a critical E2F1-regulated oncogenic factor in cervical cancer progression. The strong correlation between CDCA5 expression and poor clinical outcomes suggests its potential as both a prognostic biomarker and therapeutic target in cervical cancer treatment.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 2","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143184739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yimei Zhou, Yutong Guo, Mei Zhang, Shuqi Quan, Juan Li
{"title":"The role of RAP2 in regulation of cell volume on bone marrow mesenchymal stem cell fate determination","authors":"Yimei Zhou, Yutong Guo, Mei Zhang, Shuqi Quan, Juan Li","doi":"10.1007/s10735-025-10362-1","DOIUrl":"10.1007/s10735-025-10362-1","url":null,"abstract":"<div><p>The extracellular matrix guides cell behavior through mechanical properties, which plays a role in determining cell function and can even influence stem cell fate. Compared with adherent culture, the three-dimensional culture environment is closer to the growth conditions in vivo, but is limited by standardization of material properties and observation and measurement methods. Therefore, it is necessary to study the relationship among the three-dimensional morphological characteristics of cells, cytoskeleton, and stem cell differentiation under adherent culture conditions. Here, we control the cell volume by adjusting the cell density, microfilament cytoskeleton tension, and osmotic pressure of the culture environment, and analyze the cell morphological features and differentiation to the osteoblastic and adipogenic lineages. Based on the in vitro and in vivo results, we identify cell volume as the true reflection of the cytoskeleton tension under stress stimuli compared with cell spreading area. By adjusting cell volume, cytoskeletal tension and cell differentiation can be regulated without affecting cell spreading area. Further study shows that the Ras-related small GTPase RAP2 inhibits the activity of mechanical transducers Lamin A/C and YAP1, playing an important role in cell volume regulation of cell differentiation. In summary, our results support the close relationship between cell volume and cytoskeleton tension. The regulatory role of cell volume on cell differentiation is modulated, at least in part, by RAP2-related mechanosensitive pathways. Our insights into how cell volume regulates cell differentiation may build a bridge between two-dimensional and three-dimensional mechanical studies in cell biology.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 2","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143108326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}