{"title":"Pnky Modulates Neural Stem Cell Proliferation and Differentiation Through Activation of Wnt/β-Catenin Signaling Pathway.","authors":"Haidong Wu, Jing Huang, Xiaojing Li, Yali Song, Xuxiang Chen, Yajie Guo","doi":"10.1080/15476278.2025.2519641","DOIUrl":"10.1080/15476278.2025.2519641","url":null,"abstract":"<p><p>Neural stem cell (NSC) possess the essential properties of pluripotency and self-renewal, making them promising candidates for the treatment of neurological disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), and spinal cord injuries. While previous studies have identified the long non-coding RNAs (lncRNAs) Pnky as a regulator of NSC differentiation into neurons via RNA splicing, its role in NSC differentiation and proliferation through the Wnt/β-catenin pathway remains unclear. In this study, we investigated the mechanism by which Pnky influences the Wnt/β-catenin pathway to promote NSC differentiation into neurons. Using cck8 assays, western blot analysis, and quantitative polymerase chain reaction (qPCR), we found that Pnky knockdown significantly enhanced NSC proliferation and promoted their differentiation into neurons. Additionally, Pnky knockdown resulted in the downregulation of the neural stem cell marker Nestin and upregulation of the neuronal marker β3-Tubulin, through activation of the β-catenin signaling pathway. Conversely, inhibiting the β-catenin pathway hindered both NSC differentiation and proliferation. These findings suggest that targeting the Pnky-mediated Wnt/β-catenin pathway may offer novel strategies for the treatment, diagnosis, and drug development of central nervous system diseases.</p>","PeriodicalId":19596,"journal":{"name":"Organogenesis","volume":"21 1","pages":"2519641"},"PeriodicalIF":1.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12184132/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144310262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
OrganogenesisPub Date : 2025-12-01Epub Date: 2025-06-26DOI: 10.1080/15476278.2025.2519607
Zhenggang Wu, Jing Liu, Deju Yin, Jing Huang, Yujing Huang, Pengfei Wang
{"title":"Baicalein Alleviates Lithium-Pilocarpine-Induced Status Epilepticus by Regulating DNMT1/GABRD Pathway in Rats.","authors":"Zhenggang Wu, Jing Liu, Deju Yin, Jing Huang, Yujing Huang, Pengfei Wang","doi":"10.1080/15476278.2025.2519607","DOIUrl":"10.1080/15476278.2025.2519607","url":null,"abstract":"<p><strong>Background: </strong>Epilepsy is a common disease of the nervous system. Recent advances in epigenetics have revealed DNA methylation as a key mechanism in epilepsy pathogenesis, particularly through dysregulation of GABAergic signaling. Baicalein has been shown to have anticonvulsant and neuroprotective effects. However, its epigenetic regulatory effects on GABA receptor function remain unexplored.</p><p><strong>Methods: </strong>The status epilepticus (SE) model was induced by lithium chloride-pilocarpine (LiCl-PILO) in Sprague-Dawley (SD) rats. The rats were divided into control group, epileptic SE group and baicalein intervention group. Morris water maze (MWM) test, Nissl staining, immunofluorescence and enzyme-linked immunosorbent assay (ELISA) were used to detect cognitive functions and neuronal damage. Online sites, chromatin immunoprecipitation (ChIP) and western blotting were used to identify DNA methyltransferase 1 (DNMT1)-mediated methylation of gamma-aminobutyric acid type A receptor subunit delta (GABRD) promoter region.</p><p><strong>Results: </strong>Baicalein treatment significantly prolonged the latency of SE onset and seizure onset, and improved the development of epilepsy. Meanwhile, baicalein improved the cognitive impairment in rats induced by LiCl-PILO. After treatment with baicalein, a sustained elevation in the number of neurons and NeuN levels was observed, along with a decrease in the contents of tumor necrosis factor -alpha (TNF-α), interleukin-1β (IL-1β), and ionized calcium-binding adapter molecule 1 (Iba-1) in the hippocampus. Mechanistically, baicalein interacted with DNMT1 to suppress GABRD promoter region methylation, thus increasing GABRD protein level in the hippocampus of rats induced by LiCl-PILO.</p><p><strong>Conclusion: </strong>This study identifies DNMT1/GABRD axis as a novel epigenetic target for epilepsy intervention. Baicalein's ability to enhance tonic inhibition through demethylation of GABRD provides a groundbreaking strategy for drug-resistant epilepsy.</p>","PeriodicalId":19596,"journal":{"name":"Organogenesis","volume":"21 1","pages":"2519607"},"PeriodicalIF":1.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12203850/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144497584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
OrganogenesisPub Date : 2025-12-01Epub Date: 2025-04-27DOI: 10.1080/15476278.2025.2489673
Luzy Zhang
{"title":"MicroRNA-214-3p Delivered by Bone Marrow Mesenchymal Stem Cells-Secreted Exosomes Affects Oxidative Stress in Alzheimer's Disease Rats by Targeting CD151.","authors":"Luzy Zhang","doi":"10.1080/15476278.2025.2489673","DOIUrl":"https://doi.org/10.1080/15476278.2025.2489673","url":null,"abstract":"<p><strong>Objective: </strong>This study probed the effect of targeted regulation of CD151 by microRNA-214-3p (miR-214-3p) delivered by bone marrow mesenchymal stem cells-secreted exosomes (BMSCs-exo) on oxidative stress and apoptosis of neurons in Alzheimer's disease (AD).</p><p><strong>Methods: </strong>Rat BMSCs were isolated, from which MSCs-exo were extracted and identified. The AD rat model was established and injected with MSC-exo suspension. Meanwhile, miR-214-3p and CD151 interfering lentivirus were transfected in MSCs. After injection, learning and cognitive ability of the rats were assessed, as well as neuronal apoptosis and oxidative stress injury. miR-214-3p and CD151 levels were determined, and their relationship was explored.</p><p><strong>Results: </strong>AD rats had prolonged escape latency, weakened learning and cognitive ability, increased neuronal apoptosis in the hippocampal CA3 region, and aggravated oxidative stress. After MSC-exo injection, these changes in AD rats were partially rescued. CD151 was targeted by miR-214-3p, and MSC-exo improved AD in rats through the miR-214-3p/CD151 axis.</p><p><strong>Conclusion: </strong>MSC-exo down-regulates CD151 by targeting miR-214-3p to enhance antioxidant capacity, thereby improving the pathological injury of AD rats.</p>","PeriodicalId":19596,"journal":{"name":"Organogenesis","volume":"21 1","pages":"2489673"},"PeriodicalIF":1.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12036478/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143991800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
OrganogenesisPub Date : 2025-12-01Epub Date: 2025-04-07DOI: 10.1080/15476278.2025.2489670
Linjuan Wu, Jingchuan Lin
{"title":"Optimized Individualized Nursing Improves Recovery and Reduces Complications in ICU Patients with Severe Pneumonia.","authors":"Linjuan Wu, Jingchuan Lin","doi":"10.1080/15476278.2025.2489670","DOIUrl":"10.1080/15476278.2025.2489670","url":null,"abstract":"<p><strong>Objective: </strong>This study evaluates the effectiveness of optimized individualized nursing interventions on clinical outcomes in intensive care unit (ICU) patients with severe pneumonia.</p><p><strong>Methods: </strong>In this randomized controlled trial, 76 patients with severe pneumonia were randomized into a control group and an experimental group. Both groups received routine nursing care. On this basis, the experimental group received optimized individualized nursing. After the nursing intervention, clinical outcomes, respiratory function, coagulation function, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, and St. George's Respiratory Problems Questionnaire (SGRQ) score were assessed, and the complication and mortality rates were counted.</p><p><strong>Results: </strong>After the intervention, compared with the control group, the experimental group exhibited shorter times of fever reduction, white blood cell count recovery, and off-boarding and ICU stay, higher oxygenation index, lower rapid shallow breathing index, respiratory rate, activated partial thromboplastin time, prothrombin time, fibrinogen, and D-Dimer levels, lower APACHE II scores and SGRQ scores (<i>p</i> < 0.05). Additionally, the experimental group possessed a lower complication rate and mortality rate than the control group (<i>p</i> < 0.05).</p><p><strong>Conclusion: </strong>Implementing optimized individualized nursing can significantly enhance recovery and reduce complications in ICU patients with severe pneumonia.</p>","PeriodicalId":19596,"journal":{"name":"Organogenesis","volume":"21 1","pages":"2489670"},"PeriodicalIF":1.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11980446/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143796129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
OrganogenesisPub Date : 2025-12-01Epub Date: 2025-02-23DOI: 10.1080/15476278.2025.2460263
Yan Tan, Bijun Du, Xixi Chen, Minhong Chen
{"title":"Correlation of MicroRNA-31 with Endometrial Receptivity in Patients with Repeated Implantation Failure of <i>In Vitro</i> Fertilization and Embryo Transfer.","authors":"Yan Tan, Bijun Du, Xixi Chen, Minhong Chen","doi":"10.1080/15476278.2025.2460263","DOIUrl":"10.1080/15476278.2025.2460263","url":null,"abstract":"<p><strong>Objective: </strong>This trial probed the correlation between miR-31 expression and endometrial receptivity (ER) in patients with repeated implantation failure (RIF) of in vitro fertilization and embryo transfer (IVF-ET).</p><p><strong>Methods: </strong>A retrospective study of 80 infertility patients who underwent IVF-ET assisted conception treatment were divided into RIF group and normal pregnancy group (control group) according to the pregnancy outcome after embryo transfer. General information of both groups was collected. Endometrial tissues were collected in the middle luteal phase of the menstrual cycle before IVF-ET. miR-31 levels in endometrial tissues were measured, and endometrial tolerance indicator pulsatility index (PI), resistance index (RI), and endometrial thickness (Em) were detected. The correlation between endometrial miR-31 levels and ER indices was evaluated by Pearson method. ROC curves were utilized to analyze the efficacy of miR-31 in predicting RIF occurrence. The influencing factors of RIF were analyzed by binary Logistic regression.</p><p><strong>Results: </strong>RIF patients had increased miR-31 expression level and endometrial tolerance indicator PI, and RI while decreased Em (<i>p</i> < 0.05). miR-31 in RIF patients was positively correlated with PI and RI, and negatively correlated with Em (<i>p</i> < 0.05). The area under the curve for miR-31 to predict the occurrence of RIF was 0.899, with a sensitivity of 0.750 and a specificity of 0.950. PI, RI, and miR-31 were risk factors for developing RIF in IVF-ET women, and Em was a protective factor (<i>p</i> < 0.05).</p><p><strong>Conclusion: </strong>miR-31 in RIF patients is positively correlated with PI and RI, and negatively correlated with Em.</p>","PeriodicalId":19596,"journal":{"name":"Organogenesis","volume":"21 1","pages":"2460263"},"PeriodicalIF":1.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11853553/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Role of SUMO1 Modification of SOX9 in Cartilage Development Stimulated by Zinc Ions in Mice.","authors":"Na Xue, Jing Zhao, Jing Yin, Liang Liu, Zhong Yang, Shuchao Zhai, Xiyun Bian, Xiang Gao","doi":"10.1080/15476278.2025.2460269","DOIUrl":"10.1080/15476278.2025.2460269","url":null,"abstract":"<p><p>Zinc ions play a pivotal role in facilitating the development of cartilage in mice. Nevertheless, the precise underlying mechanism remains elusive. Our investigation was centered on elucidating the impact of zinc deficiency on cartilage maturation by modulating SUMO1 and UBC9 at both the protein and mRNA levels. We administered a regimen inducing zinc deficiency to gravid mice from E0.5 until euthanasia. Subsequently, we subjected the embryos to scrutiny employing HE, Safranin O staining and IHC. Primary chondrocytes were isolated from fetal mouse femoral condyles and utilized for Western blot analysis to discern the expression profiles of SUMO1, SUMO2/3, UBC9, SOX9, MMP13, Collagen II, RUNX2, and aggrecan. Furthermore, ATDC5 murine chondrocytes were subjected to treatment with ZnCl<sub>2</sub>, followed by RT-PCR assessment to scrutinize the expression levels of MMP13, Collagen II, RUNX2, and aggrecan. Additionally, we conducted Co-IP assays on ZnCl<sub>2</sub>-treated ATDC5 cells to explore the interaction between SOX9 and SUMO1. Our investigation unveiled that zinc deficiency led to a reduction in cartilage development, as evidenced by the HE results in fetal murine femur. Moreover, diminished expression levels of SUMO1 and UBC9 were observed in the IHC and Western blot results. Furthermore, Western blot and Co-IP assays revealed an augmented interaction between SOX9 and SUMO1, which was potentiated by ZnCl<sub>2</sub> treatment. Significantly, mutations at the SUMOylation site of SOX9 resulted in alterations in the expression patterns of crucial chondrogenesis factors. This research underscores how zinc ions promote cartilage development through the modification of SOX9 by SUMO1.</p>","PeriodicalId":19596,"journal":{"name":"Organogenesis","volume":"21 1","pages":"2460269"},"PeriodicalIF":1.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11801356/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143190193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
OrganogenesisPub Date : 2025-12-01Epub Date: 2025-04-05DOI: 10.1080/15476278.2025.2489667
Lanxia Wu, Wenxuan Sun, Linjie Huang, Lin Sun, Jinhua Dou, Guohua Lu
{"title":"Calcium Imaging in Vivo: How to Correctly Select and Apply Fiber Optic Photometric Indicators.","authors":"Lanxia Wu, Wenxuan Sun, Linjie Huang, Lin Sun, Jinhua Dou, Guohua Lu","doi":"10.1080/15476278.2025.2489667","DOIUrl":"10.1080/15476278.2025.2489667","url":null,"abstract":"<p><p>Fiber-photometric is a novel optogenetic method for recording neural activity in vivo, which allows the use of calcium indicators to observe and study the relationship between neural activity and behavior in free-ranging animals. Calcium indicators also convert changes in calcium concentration in cells or tissues into recordable fluorescent signals, which can then be observed using the system of fiber-photometric. To date, there is a paucity of relevant literature on the proper selection and application of fiber-photometric indicators. Therefore, this paper will detail how to correctly select and apply fiber-photometer indicators in four sections: the basic principle of optical fiber photometry, the selection of calcium fluorescent probes and viral vector systems, and the measurement of specific expression of fluorescent proteins in specific tissues. Therefore, the correct use of suitable fiber optic recording indicators will greatly assist researchers in exploring the link between neuronal activity and neuropsychiatric disorders.</p>","PeriodicalId":19596,"journal":{"name":"Organogenesis","volume":"21 1","pages":"2489667"},"PeriodicalIF":1.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11980459/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
OrganogenesisPub Date : 2025-12-01Epub Date: 2025-02-18DOI: 10.1080/15476278.2025.2460261
Ke Xu, Mingzhe Zhang, Xiaofeng Zou, Mingyang Wang
{"title":"Tetramethylpyrazine Confers Protection Against Oxidative Stress and NLRP3-Dependent Pyroptosis in Rats with Endometriosis.","authors":"Ke Xu, Mingzhe Zhang, Xiaofeng Zou, Mingyang Wang","doi":"10.1080/15476278.2025.2460261","DOIUrl":"10.1080/15476278.2025.2460261","url":null,"abstract":"<p><p>Tetramethylpyrazine (TMP) has been confirmed to suppress inflammation in endometriosis (EMs). Herein, this study investigated whether and how TMP affected NLRP3 inflammasomes and oxidative stress in EMs. After establishment of an EMs rat model, rats were treated with different concentrations of TMP. The size of endometriotic lesions and the latency and frequency of torsion in rats were recorded, followed by the measurement of relevant indicators (TNF-α, IL-6, IL-2, IL-10, MDA, SOD, GSH, CAT, ROS, NLRP3, ASC, GSDMD, caspase-1, Nrf2, and HO-1). The study experimentally determined that TMP treatment markedly decreased the size of endometriotic lesions and improved torsion in rats with EMs. The levels of inflammatory proteins, oxidative stress markers, NLRP3 inflammasome, and pyroptotic proteins were elevated in rats with EMs, all of which were reversed upon TMP treatment. Additionally, the activities of SOD, GSH, and CAT were lowered in rats with EMs, which were partly abrogated by TMP treatment. Furthermore, the downregulation of Nrf2 and HO-1 was counteracted by TMP treatment. To sum up, TMP represses excessive oxidative stress, NLRP3 inflammasome activation, and pyroptosis in rats with EMs. Additionally, TMP may activate the Nrf2/HO-1 pathway.</p>","PeriodicalId":19596,"journal":{"name":"Organogenesis","volume":"21 1","pages":"2460261"},"PeriodicalIF":1.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11845083/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143449601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
OrganogenesisPub Date : 2025-12-01Epub Date: 2025-06-17DOI: 10.1080/15476278.2025.2519614
Jie Chen, Libin Zou, Lu Liu, Chunfeng Wu, Mi Hu
{"title":"ORM1 Mediates Ln-IgG-Induced Podocyte Damage and Autophagy via the AMPK/mTOR Signaling.","authors":"Jie Chen, Libin Zou, Lu Liu, Chunfeng Wu, Mi Hu","doi":"10.1080/15476278.2025.2519614","DOIUrl":"10.1080/15476278.2025.2519614","url":null,"abstract":"<p><p>Podocyte damage is a central feature of lupus nephritis (LN), making the identification of potential therapeutic targets to prevent podocyte injury and improve treatment outcomes essential. ORM1 has been suggested as a significant candidate gene in LN. In this study, mouse podocytes were induced using Immunoglobulin G (IgG) extracted from lupus patients. To investigate the role of ORM1, ORM1 knockdown was performed, and the effects on podocyte viability and apoptosis were assessed using the cell counting kit-8 (CCK-8) assay and flow cytometry. Additionally, autophagy markers LC3II/I and p62 were measured by western blotting and immunofluorescence, and the expression of the AMPK/mTOR signaling pathway was evaluated using western blotting. The results showed an upregulation of ORM1 in the LN model. Upon stimulation with IgG from LN patients, ORM1 knockdown reversed the reduction in podocyte viability, decreased the apoptosis rate, and reduced the elevated levels of autophagy, followed by an increase in AMPK phosphorylation and a decrease in mTOR phosphorylation. In conclusion, these results suggest that ORM1 modulates the expression of autophagy-related components in podocytes through the AMPK/mTOR signaling pathway, thereby influencing podocyte damage in the LN model in vitro.</p>","PeriodicalId":19596,"journal":{"name":"Organogenesis","volume":"21 1","pages":"2519614"},"PeriodicalIF":1.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12184165/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144317562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
OrganogenesisPub Date : 2025-12-01Epub Date: 2025-06-26DOI: 10.1080/15476278.2025.2519649
Sen Duan, Qindong Zhang, Jinqiang Zhu, Jiaming Wang
{"title":"SS-31 Targets NOS2 to Enhance Osteogenic Differentiation in Aged BMSCs by Restoring Mitochondrial Function.","authors":"Sen Duan, Qindong Zhang, Jinqiang Zhu, Jiaming Wang","doi":"10.1080/15476278.2025.2519649","DOIUrl":"10.1080/15476278.2025.2519649","url":null,"abstract":"<p><p>This study delves into the rejuvenating effects of SS-31 on aged human Bone Marrow-Derived Mesenchymal Stem Cells (BM-MSCs), focusing on its potential to restore their diminished osteogenic differentiation capacity, a critical issue in geriatric medicine and bone tissue engineering. SS-31 significantly improved mitochondrial function, increasing ATP production by 35% and reducing ROS levels by 40% in aged BM-MSCs. Osteogenic differentiation was enhanced, as evidenced by a 2.8-fold increase in ALP activity and a 3.5-fold increase in Alizarin Red S staining intensity. Additionally, SS-31 reduced NOS2 expression by 50%, highlighting its therapeutic potential in age-related bone loss. SS-31 intervention not only normalizes mitochondrial structure and function, reducing ROS levels and enhancing oxygen consumption rates, but also targets the NOS2 gene, a potential drug target, which upon knockdown, leads to a substantial upregulation of osteogenic markers and an improvement in mitochondrial function. In conclusion, the findings of this study highlight the therapeutic potential of SS-31 in reversing the age-related decline in BM-MSC function by specifically inhibiting NOS2 expression and restoring mitochondrial function. This research provides a scientific basis for the development of new treatments for osteoporosis and other age-related bone diseases, emphasizing the importance of targeting mitochondrial function and cellular senescence in regenerative therapies.</p>","PeriodicalId":19596,"journal":{"name":"Organogenesis","volume":"21 1","pages":"2519649"},"PeriodicalIF":1.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12258809/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144507338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}