Stem Cells International最新文献

{"title":"Clinical Outcomes of Keratolimbal Allograft Transplantation With Oral Mucosal Transplantation for Limbal Stem Cell Deficiency With Symblepharon.","authors":"Shang Li, Yinghui Wang, Zhiqun Wang, Shijing Deng, Lan Lv, Ying Jie","doi":"10.1155/sci/8426444","DOIUrl":"10.1155/sci/8426444","url":null,"abstract":"<p><p><b>Objective:</b> To report preliminary clinical outcomes of keratolimbal allograft (KLAL) transplantation with oral mucosal transplantation (OMT) for the treatment of limbal stem cell deficiency (LSCD) with symblepharon. <b>Methods:</b> This is a retrospective review of patients with LSCD and symblepharon who underwent KLAL transplantation with OMT at the Department of Ophthalmology, the Capital Medical University of Beijing Tongren Hospital between 2022 and 2024. Patients with at least 3 months of postoperative follow-up and adequate pre or postoperative records were enrolled. Grades of symblepharon, corneal conjunctivalisation, vascularization, opacification, fornix depth, and best corrected visual acuity (BCVA) were evaluated preoperatively and postoperatively. In five cases, in vivo confocal microscopy (IVCM), impression cytology (IC), and immunofluorescence (IF) were performed. <b>Results:</b> At a postoperative follow-up of 8.27 ± 5.80 months (3-22 months), 10 of 11 eyes (90.91%) maintained a successful outcome. The grades of symblepharon, corneal conjunctivalisation, vascularization, and opacification were significantly improved after surgery (<i>p</i> ≤ 0.01). Significant deepening of the fornix depth in the superior (<i>p</i> ≤ 0.01) and inferior conjunctival (<i>p</i> ≤ 0.05). Two-line improvement in BCVA was seen in 8 eyes (72.73%). Recurrence of LSCD occurred in 1 eye (9.09%). Morphology and structure of corneal epithelial cells and epithelial transition around the KLAL segments were detected by IVCM, IC, and IF. <b>Conclusions:</b> From the preliminary clinical results, KLAL with OMT is a safe and effective surgical technique for LSCD with symblepharon, maintaining epithelial stability, and restoring the patient's ocular anatomy.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2025 ","pages":"8426444"},"PeriodicalIF":3.3,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12488307/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145213754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ECM Protein CYR61 Promotes Migration and Osteoblastic Differentiation of Irradiation BMSCs via Migrasomes.","authors":"Chaoting Yan, Wen Sun, Zhi Chen, Liu Liu, Pin Zhou, Yueguang Gu, Geng Wu, Kunpeng Wang","doi":"10.1155/sci/8825935","DOIUrl":"10.1155/sci/8825935","url":null,"abstract":"<p><p>Osteoradionecrosis of the jaw (ORNJ) is a complication of radiation therapy that can lead to hard-to-repair bone defects. Bone marrow mesenchymal stem cells (BMSCs) have been identified as potential \"seeds\" for restoring bone defects. In this study, we reported extracellular matrix protein cysteine-rich angiogenic inducer 61 (CYR61) to enhance the migratory and osteogenic functions of irradiated BMSCs (IR BMSCs) by migrasomes. Various assays, including alkaline phosphatase (ALP) activity assay, Cell Counting Kit-8 (CCK-8), apoptosis analysis, qRT-PCR, western blot, ALP staining, alizarin red S (ARS) staining, wound healing assay, transwell assay, and co-immunoprecipitation (co-IP) were conducted to assess the optimal radiation dose for generating IR BMSCs and migrasome functionality. Proteomics, bioinformatics analysis, gene transfection, and molecular docking were employed to identify key molecules mediating migration and osteoblastic differentiation and its downstream mechanisms. Furthermore, confocal microscopy, transmission electron microscopy (TEM), and western blot were utilized to identify migrasomes. Results showed that a radiation dose of 2 Gy inhibited migratory and osteogenic abilities of cells without significantly affecting viability. CYR61 emerged as a pivotal molecule regulating BMSC migration and osteoblastic differentiation through binding to integrin αvβ3 at the 125th aspartic acid and activating the ERK signaling pathway. We discovered that migrasomes are the key vehicle effectively delivering CYR61 to restore migration and osteogenesis of IR BMSCs. In conclusion, migrasomes-secreted CYR61 facilitating a promotional effect can regulate the migration and osteogenesis of IR BMSCs. Thus, migrasomes-origin CYR61 may serve as potential therapeutic agents for repairing ORNJ-related bone defects.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2025 ","pages":"8825935"},"PeriodicalIF":3.3,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12476934/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145193088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Embryonic Circadian Rhythm Establishment, Homeostasis, and Dysfunction During Organogenesis.","authors":"Si-Lin Chen, Hang Zhou, Yu-Mei Li, Yun-Wen Zheng","doi":"10.1155/sci/9621027","DOIUrl":"10.1155/sci/9621027","url":null,"abstract":"<p><p><b>Background:</b> Circadian rhythms play a crucial role in the management of the temporal organization of various physiological and cellular processes in mammalian cell types. These rhythms are involved in the regulation of the cell cycle and metabolism and have implications for pathogenesis and physiological homeostasis. Therapeutic approaches that target circadian regulation are emerging for the treatment of digestive disorders, metabolic diseases, and cancer. The proper coordination of cellular clocks is essential for tissue homeostasis and metabolic health. <b>Methods:</b> The exact mechanisms governing the development and regulation of the circadian clock during embryo development are still unclear. However, embryo rhythms, such as those in the suprachiasmatic nucleus (SCN), liver, kidney, adrenal gland, and intestinal system, are believed to be influenced by maternal rhythms during different stages of embryo development. These rhythms then oscillate independently from the timing marked as the key to embryo development. In this review, we synthesize our laboratory experience and summarize current research to provide insight into how circadian rhythms regulate and synchronize organ functions for growth and differentiation during embryo development. <b>Results:</b> Our laboratory experience and current research suggest that circadian rhythms are involved in the regulation of organ functions during embryo development. Maternal rhythms may entrain embryo rhythms during specific developmental stages, leading to independent oscillation and coordination of organ functions. This knowledge has implications for regenerative medicine and potential clinical applications. <b>Conclusions:</b> Circadian rhythms play a crucial role in the coordination and synchronization of organ functions for growth and differentiation during embryo development. Understanding the regulation of circadian rhythms in embryos can provide valuable information for regenerative medicine and potential clinical applications. More research is needed to fully unravel the mechanisms underlying circadian clock development and regulation during embryo development.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2025 ","pages":"9621027"},"PeriodicalIF":3.3,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12463512/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145186794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to \"lncRNA <i>CYTOR</i> Facilitates Osteogenic Differentiation of Human Periodontal Ligament Stem Cells by Modulating SOX11 via Sponging miR-6512-3p\".","authors":"","doi":"10.1155/sci/9825165","DOIUrl":"https://doi.org/10.1155/sci/9825165","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1155/2023/5671809.].</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2025 ","pages":"9825165"},"PeriodicalIF":3.3,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12453894/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145131954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mesenchymal Stem Cell Derived Exosomes Alleviates Hirschsprung-Associated Enterocolitis by Inhibiting AKT Phosphorylation in Macrophages Through miR-223.","authors":"Haosen Ji, Zheming Xu, Leiting Shen, Sisi Yang, Jingyi Jin, Chengjie Lyu, Yichao Ren, Yi Xiao, Yuebai Zhang, Shu Fang, Xiaoxia Zhao, Xiang Yan, Dengming Lai, Jinfa Tou","doi":"10.1155/sci/3218993","DOIUrl":"10.1155/sci/3218993","url":null,"abstract":"<p><p><b>Background:</b> Mesenchymal stem cells (MSCs) inhibit macrophage inflammatory response and alleviate intestinal inflammation. However, the role of MSCs in Hirschsprung-associated enterocolitis (HAEC) remains uncertain. This study aims to investigate the effects of MSCs on HAEC and the mechanisms related to macrophages and MSCs. <b>Methods:</b> Immunofluorescence was used to measure CD68 and p-AKT in colonic tissues of HSCR patients with HAEC. Ednrb^-/- mice was used as HSCR model. The proportion of colonic tissue macrophages in WT and Ednrb^-/- mice was assessed by flow cytometry. The colonic tissues injury was evaluated with HE staining and the survival curves of mice were recorded. In vitro, macrophage-induced enterocyte death was induced by lipopolysaccharide (LPS). MSCs, MSC derived exosomes, miR-223, or MK2206 were added to macrophages, and the levels of miR-223 in macrophages after exosome treatment were measured by RT-qPCR. Flow cytometry was used to assess enterocyte death, western blot was performed to measure p-AKT expression in macrophages, and enzyme-linked immunosorbent assay (ELISA) was used to detect IL-1β concentration in macrophage supernatants and serum of Edrnb ^<i>-/-</i> mice. <b>Results:</b> Increased expression of CD68 and p-AKT was observed in the colonic tissues of HAEC patients. Colonic instillation of MSCs derived exosomes significantly reduce the inflammatory score of colonic tissues and prolong the survival time of HAEC mice. In vitro, LPS-stimulated macrophages induce the phosphorylation of AKT and enterocyte death. Stimulation of macrophages with MSC-derived exosomes increased the content of miR-223. MSC-derived exosomes, miR-223 and MK2206 significantly reduce macrophage-induced enterocyte death, attenuated AKT phosphorylation in macrophages, and decreased IL-1β concentration in macrophage supernatants. <b>Conclusion:</b> Macrophages accumulate in colonic tissues during HAEC and inflammatory macrophages drive enterocyte death. MSCs derived exosomes reduce enterocyte death by suppressing AKT phosphorylation and IL-1β secretion via miR-223, and subsequently mitigate HAEC in mice. These findings suggest that MSC-derived exosomes, particularly those enriched in miR-223, may serve as a promising therapeutic strategy for the prevention or treatment of HAEC.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2025 ","pages":"3218993"},"PeriodicalIF":3.3,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12453914/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145131989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Natural Polyphenols and Mesenchymal Stem Cells: A New Insight in Bone Regenerative Medicine.","authors":"Mohammad-Sadegh Lotfi, Fatemeh B Rassouli","doi":"10.1155/sci/8019494","DOIUrl":"10.1155/sci/8019494","url":null,"abstract":"<p><p>Bone defects pose significant clinical challenges, necessitating the development of innovative strategies to effectively restore damaged bone and recover normal function. Mesenchymal stem cells (MSCs) have emerged as a promising tool for bone regeneration due to their accessibility from various sources, ease of isolation and expansion, and intrinsic ability to differentiate into osteogenic lineages with minimal ethical concerns. However, successful bone repair using MSCs requires the incorporation of biocompatible osteoinductive agents, preferably derived from natural sources. Natural polyphenols, particularly flavonoids, exhibit potent pharmaceutical properties that modulate MSC fate toward osteogenic differentiation. These secondary metabolites promote osteogenesis by interacting with key bone regulatory signaling pathways, including bone morphogenetic protein 2 (BMP2)/SMAD, wingless-related integration site (Wnt)/β-catenin, nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB), and mitogen-activated protein kinase (MAPK). Beyond their osteoinductive capacity, flavonoids possess anti-inflammatory, antibacterial, and pro-angiogenic effects, which synergistically enhance bone formation both in vitro and in vivo, thereby amplifying their therapeutic potential. This review synthesizes current insights into the interaction between MSCs and natural flavonoids, detailing the molecular mechanisms driving their synergistic effects. It also highlights recent advancements in nanoformulation-based delivery systems aimed at addressing challenges like poor solubility and bioavailability. Although preclinical data strongly support the bone-protective properties of these agents, their clinical translation remains forthcoming. Future studies must focus on optimizing delivery methods, ensuring long-term safety, and rigorously validating therapeutic efficacy across various bone disorders.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2025 ","pages":"8019494"},"PeriodicalIF":3.3,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12449111/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145114212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fabrication of 3D Collagen-Based Decellularized Biological Scaffolds Using Human Wharton's Jelly-Derived Mesenchymal Stem Cells With Differentiation Potential Toward Chondrocytes.","authors":"Fatemeh Masjedi, Zahra Heidari, Kamran Hosseini, Shahrokh Zare, Anahid Safari, Davood Mehrabani, Elmira Jalilian, Negar Azarpira, Zahra Khodabandeh","doi":"10.1155/sci/9953810","DOIUrl":"10.1155/sci/9953810","url":null,"abstract":"<p><p><b>Background:</b> Stem cell-based regenerative approaches have been developed to treat osteoarthritis (OA) and repair cartilage defects. In the present study, we fabricated a three-dimensional (3D) collagen-based decellularized biological scaffold using human Wharton's jelly-derived mesenchymal stem cells (hWJ-MSCs) and analyzed its recellularization and subsequent differentiation potential toward chondrocytes. <b>Methods:</b> MSCs were isolated from human Wharton's jelly, characterized by flow cytometry, and differentiated toward osteogenic and adipogenic lineages. hWJ-MSCs were cultured in a 3D collagen scaffold. After the matrix was deposited by the cells, the scaffold was decellularized, and new hWJ-MSCs were cultured and differentiated into chondrocytes. The efficiency of the decellularization process was assessed using hematoxylin and eosin (H&E) staining, DNA quantification, scanning electron microscopy (SEM), and Raman spectroscopy. Immunohistochemical and transcriptional evaluation of chondrogenic markers, including collagen type II, aggrecan, and osteonectin, was performed. <b>Results:</b> Prepared decellularized scaffolds showed very low levels of nucleic materials compared to intact ones. The integrity and efficiency of the decellularization process were confirmed using SEM. Moreover, a comparison of Raman spectra of intact and decellularized scaffolds demonstrated a remarkable reduction in carbohydrate, lipid, and DNA content. Three weeks after recellularization in the presence of chondrogenic medium, the immunoreactivity and expression levels of specific chondrocyte markers, including collagen type II, aggrecan, and osteonectin, significantly increased compared to negative controls. <b>Conclusion:</b> hWJ-MSCs and their use in fabricating nucleic acid-free 3D collagen-based scaffolds represent a promising in vitro model for investigating how the extracellular matrix (ECM) contributes to specific cell microenvironments. Decellularized ECM can also be utilized to develop novel, cell-free biomedical products for regenerative medicine.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2025 ","pages":"9953810"},"PeriodicalIF":3.3,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12446596/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145114196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of Oral Pathogens Associated With Pulpitis and Apical Periodontitis on Odontogenic Mesenchymal Stem Cells.","authors":"Linlong Qi, Xiaoyao Liang, Zirui Qin, Huihui Gao, Yi Zhang, Yuan Wang, Shuli Deng","doi":"10.1155/sci/5523197","DOIUrl":"10.1155/sci/5523197","url":null,"abstract":"<p><p>Dental mesenchymal stem cells (MSCs) play an essential role in the development of immature permanent teeth. Bacterial infection of the pulp and periapical tissues of immature permanent teeth, the associated oral pathogens, and their virulence factors affect the viability, proliferation, differentiation, and cytokine secretion of MSCs. Bacteria and virulence factors can also trigger an inflammatory response that induces pro-inflammatory cytokine secretion and destroys odontogenic MSCs in the pulp and periapical region, negatively affecting the development of immature permanent teeth. The present study explored the role and mechanisms of oral pathogens associated with pulpitis and apical periodontitis and their virulence factors concerning odontogenic MSCs. The findings can contribute to the clinical treatment of pulpitis and apical periodontitis of immature permanent teeth, providing a theoretical basis for improving its clinical efficacy.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2025 ","pages":"5523197"},"PeriodicalIF":3.3,"publicationDate":"2025-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12414624/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145024203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human Umbilical Cord Mesenchymal Stem Cells Inhibit the Progression of Osteoarthritis by Suppressing NLRP3-Mediated Synovial Inflammation in the Early Stages of the Disease.","authors":"Yu Li, Yu Ouyang, Ruibo Lang, Jing He, Shuo Zheng, Chunchun Ao, Yijia Jiang, Huan Xiao, Mao Li, Changyong Li, Dongcheng Wu","doi":"10.1155/sci/7558817","DOIUrl":"10.1155/sci/7558817","url":null,"abstract":"<p><p>Osteoarthritis (OA) is the leading joint disease that causes joint pain and disability. Despite increasing progress regarding the therapeutic potential of human umbilical cord mesenchymal stem cells (UC-MSCs) for OA, effective strategies for the treatment of OA using UC-MSCs have not yet been developed in clinical practice. Our present study has proven that the early stage in OA rats is the main development stage of nod-like receptor heat protein domain protein 3 (NLRP3)-mediated synovial inflammation. The middle stage in OA rats is the main development stage of chondrocyte apoptosis. The late stage in OA rats is the main development stage of synovial fibrosis. The treatment of UC-MSCs in the early and middle stages of OA significantly reduced cartilage damage in rats, and improved the pathological structure of the knee joint. In comparison, UC-MSCs effectively reduced chondrocyte apoptosis in the early and middle stages of OA rats, but they only effectively reduced NLRP3-mediated synovial inflammation in the early stages of OA rats. Experiments in vitro showed that UC-MSCs could inhibit NLRP3-mediated pyroptosis of rat primary synovial cells (Rat-scs). In conclusion, our findings suggest that UC-MSCs exert therapeutic effects on OA, at least in part, through inhibiting NLRP3-mediated synovial inflammation in the early stage of OA.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2025 ","pages":"7558817"},"PeriodicalIF":3.3,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12413943/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145016180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Imbalance of Bone Homeostasis Caused by Nrf2 Deficiency Leads to Bone Loss in OVX Rats.","authors":"Pan Sun, Zhiqiang Wang, Sainan Chen, Xuzheng Chen, Fen Zhou, Chutian Zhang, Juan Yang, Yunmei Huang, Yanping Lin","doi":"10.1155/sci/7214250","DOIUrl":"10.1155/sci/7214250","url":null,"abstract":"<p><p><b>Objective:</b> Postmenopausal osteoporosis (PMOP) is a common bone metabolic disorder in middle-aged and elderly women, yet its pathogenesis remains unclear. This study investigates the effect of nuclear factor erythroid 2-related factor 2 (Nrf2) deficiency on bone homeostasis to provide insight into the mechanisms underlying PMOP. <b>Methods:</b> Sixteen female SD rats were randomly assigned to Sham and ovariectomized (OVX) groups. After 12 weeks, bone homeostasis disruption and Nrf2-mediated oxidative stress responses in bone tissue cells were assessed. Nrf2 expression was modulated in UMR-106 osteoblast-like cells and RAW264.7 macrophage-derived osteoclast precursor cells through knockdown or pharmacological activation. The effects on osteogenic function and osteoclast differentiation under oxidative stress were then evaluated. <b>Results:</b> The OVX group of rats exhibited a disruption in bone homeostasis, potentially attributable to the reduced expression of Nrf2 and its downstream antioxidant enzymes, coupled with elevated levels of oxidative stress. Nrf2 knockdown impaired osteogenic capacity in UMR-106 cells and enhanced osteoclast differentiation in RAW264.7 cells. In contrast, activation of Nrf2 using tert-butylhydroquinone (TBHQ) promoted bone formation and suppressed osteoclast differentiation and bone resorption. <b>Conclusion:</b> Nrf2 deficiency may contribute to PMOP by disrupting bone homeostasis. Activation of Nrf2 may represent a potential therapeutic strategy for restoring bone balance and treating PMOP.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2025 ","pages":"7214250"},"PeriodicalIF":3.3,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12411055/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145016209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}