International Journal of Experimental Pathology最新文献

{"title":"Muscle fibre morphometric analysis (MusMA) correlates with muscle function and cardiovascular risk prognosis","authors":"Larisse Longo,&nbsp;Bárbara Jonson Bartikoski,&nbsp;Valessa Emanoele Gabriel de Souza,&nbsp;Fernando Salvati,&nbsp;Carolina Uribe-Cruz,&nbsp;Guido Lenz,&nbsp;Ricardo Machado Xavier,&nbsp;Mário Reis Álvares-da-Silva,&nbsp;Eduardo Cremonese Filippi-Chiela","doi":"10.1111/iep.12504","DOIUrl":"10.1111/iep.12504","url":null,"abstract":"<p>Morphometry of striated muscle fibres is critical for monitoring muscle health and function. Here, we evaluated functional parameters of skeletal and cardiac striated muscle in two experimental models using the Morphometric Analysis of Muscle Fibre tool (MusMA). The collagen-induced arthritis model was used to evaluate the function of skeletal striated muscle and the non-alcoholic fatty liver disease model was used for cardiac striated muscle analysis. After euthanasia, we used haeamatoxylin and eosin stained sections of skeletal and cardiac muscle to perform muscle fibre segmentation and morphometric analysis. Morphometric analysis classified muscle fibres into six subpopulations: normal, regular hypertrophic, irregular hypertrophic, irregular, irregular atrophic and regular atrophic. The percentage of atrophic fibres was associated with lower walking speed (<i>p</i> = 0.009) and lower body weight (<i>p</i> = 0.026), respectively. Fibres categorized as normal were associated with maximum grip strength (<i>p</i> &lt; 0.001) and higher march speed (<i>p</i> &lt; 0.001). In the evaluation of cardiac striated muscle fibres, the percentage of normal cardiomyocytes negatively correlated with cardiovascular risk markers such as the presence of abdominal adipose tissue (<i>p</i> = .003), miR-33a expression (<i>p</i> = .001) and the expression of miR-126 (<i>p</i> = .042) Furthermore, the percentage of atrophic cardiomyocytes correlated significantly with the Castelli risk index II (<i>p</i> = .014). MusMA is a simple and objective tool that allows the screening of striated muscle fibre morphometry, which can complement the diagnosis of muscle diseases while providing functional and prognostic information in basic and clinical research.</p>","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"105 3","pages":"100-113"},"PeriodicalIF":3.0,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140897872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microfluidics-based EGFR mutation detection and its implication in the resource-limited clinical setting","authors":"Pradnya Joshi,&nbsp;Prachi Gogte,&nbsp;Trupti Pai,&nbsp;Mamta Gurav,&nbsp;Dipika Dhanawade,&nbsp;Nupur Karnik,&nbsp;Gauri Deshpande,&nbsp;Rajiv Kaushal,&nbsp;Omshree Shetty","doi":"10.1111/iep.12503","DOIUrl":"10.1111/iep.12503","url":null,"abstract":"<p>Management of lung cancer today obligates a mutational analysis of the epidermal growth factor receptor (<i>EGFR)</i> gene particularly when Tyrosine Kinase Inhibitor (TKI) therapy is being considered as part of prognostic stratification. This study evaluates the performance of automated microfluidics-based <i>EGFR</i> mutation detection and its significance in clinical diagnostic settings. Formalin-fixed, paraffin-embedded (FFPE) samples from NSCLC patients (<i>n</i> = 174) were included in a two-phase study. Phase I: Validation of the platform by comparing the results with conventional real-time PCR and next-generation sequencing (NGS) platform. Phase II: <i>EGFR</i> mutation detection on microfluidics-based platform as part of routine diagnostics workup. The microfluidics-based platform demonstrates 96.5% and 89.2% concordance with conventional real-time PCR and NGS, respectively. The system efficiently detects mutations across the <i>EGFR</i> gene with 88.23% sensitivity and 100% specificity. Out of 144 samples analysed in phase II, the platform generated valid results in 94% with mutation detected in 41% of samples. This microfluidics-based platform can detect as low as 5% mutant allele fractions from the FFPE samples. Therefore the microfluidics-based platform is a rapid, complete walkaway, with minimum tissue requirement (two sections of 5 μ thickness) and technical skill requirement. The method can detect clinically actionable <i>EGFR</i> mutations efficiently and can be considered a reliable diagnostic platform in resource-limited settings. From receiving samples to reporting the results this platform provides accurate data without much manual intervention. The study helped to devise an algorithm that emphasizes effective screening of the NSCLC cases for <i>EGFR</i> mutations with varying tumour content. Thus it helps in triaging the cases judiciously before proceeding with multigene testing.</p>","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"105 3","pages":"90-99"},"PeriodicalIF":3.0,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140876421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trilobatin contributes to the improvement of myopathy in a mouse model of Duchenne muscular dystrophy","authors":"Túlio de Almeida Hermes,&nbsp;Paula Fratini,&nbsp;Beatriz Godinho Nascimento,&nbsp;Laís Leite Ferreira,&nbsp;Giuliana Petri,&nbsp;Fernando Luiz Affonso Fonseca,&nbsp;Alzira Alves de Siqueira Carvalho,&nbsp;David Feder","doi":"10.1111/iep.12502","DOIUrl":"10.1111/iep.12502","url":null,"abstract":"<p>Duchenne muscular dystrophy (DMD) occurs due to genetic mutations that lead to a deficiency in dystrophin production and consequent progressive degeneration of skeletal muscle fibres, through oxidative stress and an exacerbated inflammatory process. The flavonoid trilobatin (TLB) demonstrates antioxidant and anti-inflammatory potential. Its high safety profile and effective action make it a potent therapy for the process of dystrophic muscle myonecrosis. Thus, we sought to investigate the action of TLB on damage in a DMD model, the mdx mouse. Eight-week-old male animals were treated with 160 mg/kg/day of trilobatin for 8 weeks. Control animals were treated with saline. Following treatment, muscle strength, serum creatine kinase (CK) levels, histopathology (necrotic myofibres, regenerated fibres/central nuclei, Feret's diameter and inflammatory area) and the levels of catalase and NF-κB (western blotting) of the quadriceps (QUA), diaphragm (DIA) and tibialis anterior (TA) muscles were measured. TLB was able to significantly increase muscle strength and reduce serum CK levels in dystrophic animals. The QUA of mdx mice showed a reduction in catalase and the number of fibres with a centralized nucleus after treatment with TLB. In the DIA of dystrophic animals, TLB reduced the necrotic myofibres, inflammatory area and NF-κB and increased the number of regenerated fibres and the total fibre diameter. In TA, TLB increased the number of regenerated fibres and reduced catalase levels in these animals. It is concluded that in the mdx experimental model, treatment with TLB was beneficial in the treatment of DMD.</p>","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"105 2","pages":"75-85"},"PeriodicalIF":3.0,"publicationDate":"2024-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140110222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TGFβR1 inhibition drives hepatocellular carcinoma proliferation through induction of toll-like-receptor signalling","authors":"Fatma El Zahraa Ammar Mohamed,&nbsp;Bedair Dewidar,&nbsp;Tao Lin,&nbsp;Matthias P. Ebert,&nbsp;Steven Dooley,&nbsp;Nadja M. Meindl-Beinker,&nbsp;Seddik Hammad","doi":"10.1111/iep.12501","DOIUrl":"10.1111/iep.12501","url":null,"abstract":"<p>Transforming growth factor (TGF)-β and toll-like receptors (TLRs) have been shown to independently modulate the proliferation of hepatocellular carcinoma (HCC). Since a direct cross-talk between these two signalling pathways in HCC has not been clearly described before, we aimed here to explore the possibility of such interaction. A human HCC tissue array (<i>n</i> = 20 vs. four control samples), human HCC samples (<i>n</i> = 10) and steatohepatitis-driven murine HCC samples (control, NASH and HCC; <i>n</i> = 6/group) were immunostained for TGFβR1, pSMAD2, TRAF6, IRAK1 and PCNA. The results were confirmed by immunoblotting. Effects of constant activation of the SMAD pathway by constitutive expression of ALK5 or knockdown of mediators of TLR signalling, IRAK1 and MyD88, on HCC proliferation, were investigated in the HCC cell line (HUH-7) after treatment with TGFβ1 cytokine or TGFβR1 kinase inhibitor (LY2157299) using PCNA and MTS assay. TGFβR1 expression is decreased in human and murine HCC and associated with downregulated pSMAD2, but increased IRAK1, TRAF6 and PCNA staining. TGFβR1 kinase inhibition abolished the cytostatic effects of TGFβ1 and led to the induction of IRAK1, pIRAK1 and elevated mRNA levels of TLR-9. Overexpression of ALK5 and knockdown of MyD88 or IRAK1 augmented the cytostatic effects of TGFβ1 on HUH-7. In another epithelial HCC cell line, that is, HepG2, TGFβR1 kinase inhibitor similarly elevated cellular proliferation. There is a balance between the canonical SMAD-driven tumour-suppressing arm and the non-canonical tumour-promoting arm of TGFβ signalling. Disruption of this balance, by inhibition of the canonical pathway, induces HCC proliferation through TLR signalling.</p>","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"105 2","pages":"64-74"},"PeriodicalIF":3.0,"publicationDate":"2024-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139702497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MiR-22-3p facilitates bone marrow mesenchymal stem cell osteogenesis and fracture healing through the SOSTDC1-PI3K/AKT pathway","authors":"Chunqiu Wang,&nbsp;Xinguo Wang,&nbsp;Hui Cheng,&nbsp;Jiahu Fang","doi":"10.1111/iep.12500","DOIUrl":"10.1111/iep.12500","url":null,"abstract":"<p>Bone fractures are the most common form of musculoskeletal trauma worldwide. Numerous microRNAs (miRNAs) have been suggested to be participants in regulating bone-related diseases. Recent studies revealed the regulatory role of miR-22-3p in osteogenic differentiation, but its role in fracture healing has not been investigated previously. Here, a rat femoral fracture model was established, Bone marrow mesenchymal stem cells (BMSCs) were isolated to detect the specific function and underlying mechanisms of miR-22-3p. MiR-22-3p and sclerostin domain-containing 1 (SOSTDC1) expression was determined by RT-qPCR and immunohistochemistry staining. The levels of proteins associated with osteogenic differentiation were assessed by western blotting. Flow cytometry was conducted to identify the isolated rat BMSCs. Alizarin red staining, alkaline phosphatase staining and Oil Red O staining were used to evaluate the osteogenic and adipogenic differentiation of rat BMSCs. The interaction between miR-22-3p and SOSTDC1 was verified using a luciferase reporter assay. Haematoxylin and Eosin (H&amp;E) staining of the bone tissues was performed to analyse the effect of miR-22-3p on histopathological changes in vivo. MiR-22-3p was downregulated in the callus tissues of rat femoral fracture, while the expression of SOSTDC1 was upregulated. The isolated rat BMSCs had the capacity for both osteogenic and adipogenic differentiation. The differentiation capacity of BMSCs into osteoblasts was increased by miR-22-3p overexpression. MiR-22-3p activated the PI3K/AKT pathway by targeting SOSTDC1. SOSTDC1 overexpression and PI3K/AKT signalling inhibitor LY294002 abolished the enhancing effect of miR-22-3p overexpression on the osteogenesis of BMSCs. Thus MiR-22-3p facilitated the femoral fracture healing in rats. MiR-22-3p overexpression promoted fracture healing via the activation of PI3K/AKT pathway by targeting SOSTDC1.</p>","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"105 2","pages":"52-63"},"PeriodicalIF":3.0,"publicationDate":"2023-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139048647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased accumulation of the advanced glycation endproduct Ne(carboxymethyl) lysine in the intramyocardial vasculature in patients with epicarditis","authors":"U Baylan,&nbsp;A Baidoshvili,&nbsp;S Simsek,&nbsp;CG Schalkwijk,&nbsp;HWM Niessen,&nbsp;PAJ Krijnen","doi":"10.1111/iep.12499","DOIUrl":"10.1111/iep.12499","url":null,"abstract":"<p>Advanced glycation end-products (AGEs) are implicated in the pathogenesis of vascular disease. In previous studies we have found increased deposition of N(e)-(carboxymethyl)lysine (CML) in intramyocardial vasculature in the heart in acute myocardial infarction and myocarditis. It is known that the process of inflammation plays a role in the formation of AGEs. In this study we have explored the presence of CML (a major AGE) in the heart of patients with epicarditis using a monoclonal anti-CML antibody. Nine patients with epicarditis (<i>n</i> = 9) died and their hearts were used for this study, control were hearts from patients who died from conditions unrelated to heart disease and without signs of myocarditis or epicarditis CML deposition and complement were significantly increased in patients with epicarditis compared to control hearts. Thus epicarditis increases CML depositions in the intramyocardial vasculature.</p>","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"105 2","pages":"48-51"},"PeriodicalIF":3.0,"publicationDate":"2023-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/iep.12499","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138561843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circular RNA circVAPA modulates macrophage pyroptosis in sepsis-induced acute lung injury through targeting miR-212-3p/Sirt1/Nrf2/NLRP3 axis","authors":"Yanjing Huang,&nbsp;Jinquan Lin,&nbsp;Zhiwei Wu,&nbsp;Yiming Li","doi":"10.1111/iep.12497","DOIUrl":"10.1111/iep.12497","url":null,"abstract":"<p>Sepsis-induced acute lung injury (ALI) is an inflammatory condition involving the pyroptosis of macrophages. This study investigated the role of circular RNA hsa_circ_0006990 (circVAPA) in regulating macrophage pyroptosis in ALI and the underlying mechanisms. The expression pattern of circVAPA was examined in the mouse model of ALI and in the LPS-treated RAW264.7 macrophage cell line. Lung tissue damage was evaluated by haematoxylin and eosin staining, immunohistochemistry and a myeloperoxidase activity assay. The molecular mechanisms were investigated by luciferase reporter assay, western blot, RT-qPCR and ELISA. circVAPA was down-regulated in the lung tissues of ALI mice and LPS-induced RAW264.7 cells. circVAPA over-expression alleviated lung tissue injury and dampened LPS-induced pyroptosis and Th17-associated inflammatory responses. miR-212-3p was identified as a target of circVAPA, and miR-212-3p negatively regulated the expression of Sirt1. Sirt1 knockdown largely abolished the effect of circVAPA over-expression on pyroptosis. CircVAPA/miR-212-3p/Sirt1 axis also regulates Nrf2 and NLRP3 expression upon LPS challenge. By targeting miR-212-3p, circVAPA over-expression negatively regulates the expression of Sirt1 and pyroptosis-related factors (Nrf2 and NLRP3), which alleviates the inflammatory damages in sepsis-induced ALI.</p>","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"105 1","pages":"21-32"},"PeriodicalIF":3.0,"publicationDate":"2023-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138487467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-inflammatory and healing effect of the polysaccharidic extract of Opuntia ficus-indica cladodes in cutaneous excisional wounds in rats","authors":"Beatriz Lima Adjafre,&nbsp;Iásly Costa Lima,&nbsp;Ana Paula Negreiros Nunes Alves,&nbsp;Rafael Aires Lessa,&nbsp;Arcelina Pacheco Cunha,&nbsp;Maria Gonçalves Pereira,&nbsp;Ana Maria Sampaio Assreuy,&nbsp;Mário Rogério Lima Mota","doi":"10.1111/iep.12498","DOIUrl":"10.1111/iep.12498","url":null,"abstract":"<p>This study aimed to investigate the anti-inflammatory and wound healing effects of the polysaccharide extract from <i>Opuntia ficus-indica</i> cladodes (TPL-Ofi) using a rat cutaneous wound model. After anaesthesia, four 7-mm-diameter dorsal wounds per animal (<i>n</i> = 6/group for each experimental day of evaluation) were created in female Wistar rats using a surgical punch. The animals were treated topically twice daily with TPL-Ofi (0.01–1%; treated group) or sterile saline (control group) for a period of 21 days. Ulcerated tissue was collected for analysis of histological parameters (inflammation score, number of polymorphonuclear, mononuclear, fibroblast/myofibroblasts and blood vessels), immunohistochemical (fibroblast growth factor 2 [FGF-2]) and oxidative stress markers (myeloperoxidase [MPO] and glutathione [GSH]). After 21 days of treatment, body weight, net organ weight and plasma biochemical levels were measured. TPL-Ofi, containing a total carbohydrate content of 65.5% and uronic acid at 2.8%, reduced oedema on the second day and increased the nociceptive threshold on the second and third days. TPL-Ofi reduced mononuclear infiltrate on the second and MPO activity on the fifth day. TPL-Ofi increased GSH levels on the second day, as well as fibroblast/myofibroblasts counts, neoangiogenesis and FGF-2 levels on the fifth and seventh days. No changes were observed in body weight, net organ weight or toxicology assessment. Topical application of TPL-Ofi exhibited anti-inflammatory and antinociceptive effects, ultimately improving wound healing in cutaneous wounds.</p>","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"105 1","pages":"33-44"},"PeriodicalIF":3.0,"publicationDate":"2023-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138290947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring effect of M2 macrophages on experimental full-thickness wound healing in streptozotocin-induced diabetic rats","authors":"Parmis Khoshnoudi,&nbsp;Soroush Sabiza,&nbsp;Mohammad Khosravi,&nbsp;Babak Mohamadian","doi":"10.1111/iep.12496","DOIUrl":"10.1111/iep.12496","url":null,"abstract":"<p>Diabetes mellitus is one of the most prevalent medical conditions, in both humans and animals. People with diabetes mellitus often experience slower than normal wound healing, making it a serious health concern. This study investigates the effect of M2 differentiated macrophages on full-thickness wound healing in white Westar rats exposed to streptozocin 70 mg/kg. A full-thickness skin defect with dimensions of 2 × 2 cm was created on the back of all the animals, and their blood sugar was simultaneously assessed. The monocytes were isolated from blood samples using the plastic adherence method and were exposed to dexamethasone (5–10 <i>μ</i>) for 24 h. Subsequently, they were washed with PBS and incubated in fresh cell culture medium for 5 days. The differentiated M2 cells were injected into four points of the experimental ulcers of the treatment group. Macroscopic and microscopic changes were evaluated and compared over a period of two weeks between the test and control groups. The infusion of these cells a few days after wounding enhances wound healing parameters significantly, as evidenced by an increase in germinating tissue formation, wound contraction, inflammation reduction, and collagen increase in the treated group.</p>","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"105 1","pages":"13-20"},"PeriodicalIF":3.0,"publicationDate":"2023-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134648932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Notoginsenoside R1 promotes osteogenic differentiation of human bone marrow mesenchymal stem cells via ERα/GSK-3β/β-catenin signalling pathway","authors":"Wei Lu,&nbsp;Yuanxin Shi,&nbsp;Minglei Qian","doi":"10.1111/iep.12494","DOIUrl":"10.1111/iep.12494","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Human bone marrow mesenchymal stem cells (hBMSCs) are attractive therapeutic agents for bone tissue regeneration owing to their osteogenic differentiation potential. Notoginsenoside R1 (NGR1) is a novel phytoestrogen with diverse pharmacological activities. Here, we probed whether NGR1 has an effect on the osteogenic differentiation of hBMSCs. EdU, CCK-8 and Transwell assays were used to measure proliferation and migration of hBMSCs after treatment with different doses of NGR1. hBMSCs were treated with osteogenic differentiation induction medium for osteogenesis. Alizarin red S (ARS) and alkaline phosphatase (ALP) staining were used to measure mineralized nodule formation and ALP activity in hBMSCs, respectively. ICI 182780, an antagonist of oestrogen receptor alpha (ERα) was used to inhibit ERα expression. The results showed that NGR1 enhanced hBMSC proliferation and migration. NGR1 increased ALP activity and mineralized nodule formation as well as promoting <i>ALP</i>, <i>RUNX2</i> and <i>OCN</i> expression in hBMSCs. NGR1 enhanced ERα expression and promoted GSK-3β/β-catenin signal transduction in hBMSCs. ICI 182780 reversed NGR1-mediated activation of the GSK-3β/β-catenin signalling and promoted an effect on hBMSC behaviour. Thus NGR1 promotes proliferation, migration and osteogenic differentiation of hBMSCs via the ERα/GSK-3β/β-catenin signalling pathway.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"105 1","pages":"4-12"},"PeriodicalIF":3.0,"publicationDate":"2023-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71412173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}