Current molecular medicine最新文献

{"title":"Exercise Alleviates Atherosclerosis Through the Modulation of the NLRP3 Inflammasome.","authors":"Xuan Liu, Shujuan Hu, Xianwang Wang, Yuqing Ding","doi":"10.2174/0115665240368171250419113225","DOIUrl":"https://doi.org/10.2174/0115665240368171250419113225","url":null,"abstract":"<p><p>Atherosclerosis (AS) is a chronic inflammatory disease closely associated with endothelial dysfunction and oxidative stress. The NOD-like receptor protein 3 (NLRP3) inflammasome, a key regulator of inflammatory responses, can exacerbate the progression of AS when activated. Growing evidence suggests that exercise, as a non-pharmacological intervention, can alleviate the progression of AS by modulating the activity of NLRP3 inflammasome. This review discusses how exercise influences the development of AS through the regulation of NLRP3 inflammasome and the underlying molecular mechanism. This study introduces the structure and activation mechanisms of NLRP3 inflammasome, as well as its role in AS. And summarizes how exercise can ameliorate endothelial dysfunction, regulate lipid metabolism, and suppress oxidative stress and inflammation by affecting the expression and activity of NLRP3 inflammasome, thereby exerting a beneficial impact on AS. Additionally, we explore the effects of exercise on the downstream inflammatory cytokines of NLRP3 inflammasome and how this regulation could help to slow the progression of AS. These findings underscore the therapeutic relevance of exercise in the prevention and treatment of AS. It provides new insights into the role of exercise interventions in the management of AS and lays a theoretical foundation for the development of innovative treatment strategies for cardiovascular disease. Given that the NLRP3 inflammatome plays an important role in the pathogenesis and treatment of AS, exercise therapy strategies targeting the NLRP3 inflammatome will help promote the development of precision medicine for AS.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143986765","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":"Prognostic Value and Immunological Role of CBX7 in Lung Adenocarcinoma.","authors":"Lingzheng Yang, Yutang Huang, Wenlu Mo, Lanxiang Wu, Chunjie Wen","doi":"10.2174/0115665240374044250416021616","DOIUrl":"https://doi.org/10.2174/0115665240374044250416021616","url":null,"abstract":"<p><strong>Background: </strong>Chromobox 7 (CBX7) has been implicated in the progression of various malignant tumors, but its clinical relevance in lung adenocarcinoma (LUAD) remains poorly understood. This study aimed to investigate the expression, prognostic value, biological functions, and immunological role of CBX7 in LUAD.</p><p><strong>Methods: </strong>CBX7 expression in LUAD and adjacent normal tissues was analyzed using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. Kaplan-Meier curves and Cox risk regression evaluated prognostic significance. Various algorithms assessed the correlation between CBX7 and immune microenvironment. The expression of CBX7 in LUAD tissues was detected by RT-qPCR, western blotting, and immunohistochemistry. The function of CBX7 in LUAD was further investigated by in vitro and in vivo experiments.</p><p><strong>Results: </strong>CBX7 expression significantly downregulated LUAD, which was associated with aberrant DNA methylation. Decreased CBX7 expression correlated with advanced tumor stage and poor prognosis. Notably, CBX7 is associated with immune cell infiltration and immune checkpoints, highlighting its potential role in guiding immunotherapy. Functional experiments demonstrated that CBX7 overexpression suppressed the malignant phenotype of LUAD cells, while CBX7 knockdown promoted tumor progression.</p><p><strong>Conclusion: </strong>We conducted a systematic analysis of the diagnostic, prognostic, and immunological significance of CBX7 in LUAD, and found that it might serve as a diagnostic marker and therapeutic target in the future.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143968031","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":"Ginsenoside Rg1 Attenuates Muscle Atrophy in Hyperglycemic Conditions, Inactivity and Protein Deprivation Models via AKT/mTOR Pathway Activation.","authors":"Xu He, Yan Li, Jun Chen, Li Zhang, Yan Huang, Ying Zhou, Jing Li","doi":"10.2174/0115665240355315250414051525","DOIUrl":"https://doi.org/10.2174/0115665240355315250414051525","url":null,"abstract":"<p><strong>Background: </strong>Muscle atrophy, a debilitating condition prevalent in diabetes and extended periods of immobilization, lacks robust therapeutic strategies. This investigation examines ginsenoside Rg1's therapeutic potential in counteracting muscle atrophy under hyperglycemic conditions and in experimental models of immobilization and dietary protein restriction.</p><p><strong>Methods: </strong>C2C12 murine myoblasts were cultured under variable glucose concentrations and treated with or without Rg1. Multiple cellular parameters were evaluated, including cell viability, apoptotic indices, cell cycle distribution, and protein synthesis rates. The activation status of the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling cascade and expression of atrophy-related markers were quantified using qRT-PCR and Western blot analyses. In parallel animal studies, rats were subjected to either immobilization or protein restriction protocols, with or without Rg1 administration. Muscle function, mass, and relevant biomarkers were evaluated.</p><p><strong>Results: </strong>Hyperglycemic conditions significantly compromised C2C12 myoblast viability, triggered apoptotic pathways, and disrupted normal cell cycle progression. Rg1 administration effectively attenuated these detrimental effects through enhanced AKT/mTOR pathway activation, upregulation of Myogenin (MyoG) expression, and suppression of atrophy-associated markers. In the rat models, Rg1 supplementation significantly ameliorated muscle deterioration, maintaining muscle mass, contractile force, and exercise tolerance, while simultaneously modulating atrophy signaling pathways and attenuating inflammatory responses. The protective effects of Rg1 were abrogated after the co-treatment with an AKT inhibitor.</p><p><strong>Conclusion: </strong>Ginsenoside Rg1 exhibits significant protective properties against muscle atrophy under hyperglycemic conditions and in experimental models of immobilization and protein restriction, primarily mediated through activation of the AKT/mTOR signaling pathway. These findings establish Rg1 as a promising therapeutic candidate for the treatment of muscle atrophy.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143968696","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":"Dihydroorotate Dehydrogenase as a Modulator of Ferroptosis in Myocardial Ischemia-Reperfusion Injury.","authors":"Mihribangvl Alip, Ziao Guo, Siwei Yang, Anikezi Wuji, Aikebaier Yasen, Bingjie Han, Munawaer Muaibati, Hongfu Wu, Xiaojun Cui","doi":"10.2174/0115665240305282241219144313","DOIUrl":"10.2174/0115665240305282241219144313","url":null,"abstract":"<p><strong>Introduction: </strong>Ferroptosis is increasingly acknowledged as a pivotal contributor to myocardial cell injury in ischemia-reperfusion (I/R). As a central enzyme in the pyrimidine synthesis pathway, dihydroorotate dehydrogenase (DHODH) is implicated in maintaining redox homeostasis and is thought to act as a protective agent against ferroptosis. Despite this association, the specific contributions of DHODH to myocardial ischemia-reperfusion injury (MIRI) and its cardioprotective potential remain inadequately elucidated.</p><p><strong>Aim: </strong>This study aimed to delineate the role of DHODH in MIRI and assess its capacity to modulate ferroptosis in cardiomyocytes.</p><p><strong>Methods: </strong>We utilized AC16 cardiomyocytes to establish an in vitro MIRI model to investigate the role of DHODH in ferroptosis. We quantitatively analyzed DHODH expression during I/R injury, along with its distribution in cytoplasmic and mitochondrial compartments. Cells pretreated with dihydroorotate (DHO) and orotate (OA)-the substrate and product of DHODH, respectively-provided a basis for assessing their susceptibility to ferroptosis. By employing siRNA to suppress DHODH expression, we delved into the underlying mechanisms of DHODH's protective role against I/Rinduced ferroptosis, focusing on oxidative stress and mitochondrial dysfunction.</p><p><strong>Results: </strong>Our findings reveal a significant induction of DHODH expression during ferroptosis in the AC16 I/R model. DHO pretreatment conferred resistance to ferroptosis, while OA pretreatment rendered cells more susceptible. Notably, DHODH silencing aggravated ferroptosis indicators, mainly through increased oxidative stress and mitochondrial dysfunction.</p><p><strong>Conclusion: </strong>DHODH emerges as a key modulator of ferroptosis in the context of MIRI, offering protection predominantly through its antioxidative functions and maintenance of mitochondrial integrity.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143983889","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":"Protease-Activated Receptor 2 Promotes Crohn's Disease-Associated Colonic Fibrosis through Fibroblast Activation.","authors":"Zhaohui Wang, Bin Liu, Chenghao Chu, Fubao Liu","doi":"10.2174/0115665240351860250403112214","DOIUrl":"https://doi.org/10.2174/0115665240351860250403112214","url":null,"abstract":"<p><strong>Aims: </strong>To clarify the roles of PAR-2 (protease-activated receptor 2) in Crohn's disease-associated colonic fibrosis.</p><p><strong>Background: </strong>G protein-coupled receptor, termed PAR-2, is triggered after serine proteases. Through activating genes encoding extracellular matrix proteins and proinflammatory cytokines, PAR-2 triggering promotes inflammatory / pro-fibrotic pathways. Although PAR-2 is highly expressed within the digestive system, its significance within colonic fibrosis (CF) has not yet been probed.</p><p><strong>Objective: </strong>The role of PAR-2 in Crohn's disease-related colonic fibrosis and its possible regulatory mechanisms has been investigated.</p><p><strong>Methods: </strong>PAR-2 expression was assessed variably in the colon of human and model mice. Immunofluorescence assay was used to analyze the phenotypic changes of fibroblasts after PAR-2 activation in the lamina propria. In in vitro assays, we explored the roles of PAR-2 in CCD-18Co fibroblasts treated with PAR-2 inhibitor ENMD-1068 and PAR-2 agonist SLIGRL-NH2.</p><p><strong>Results: </strong>PAR-2 was highly expressed in the subepithelial layer surrounding colonic crypts of CD patients or murine fibrosis cohort. Colonic PAR-2 expression was consistent with collagen deposition. Decreasing PAR-2 in experimental colon fibrosis caused a decrease in the amount of colonic collagen and histological fibrosis, followed by a reduction in colonic fibroblast activation. PAR-2 activation enhanced CF by showing a profibrogenic phenotype and collagen synthesis within CCD-18Co fibroblasts.</p><p><strong>Conclusion: </strong>Our results show that PAR-2 activation could upregulate extracellular matrix (ECM) proteomic levels, encourage CF, and cause a pro-fibrogenic phenotype within human colonic myofibroblasts.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143988941","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":"Inhibition of S100A12 Attenuates LPS-Induced Endothelial Barrier Dysfunction in HPMECs through the JAK2/STAT3 Signaling Pathway.","authors":"Ye Shen, Xiangming Ye, Lingzhi Jiang, Hengjie Li, Yanli Zhang, Wenmin Wang, Hui Mao","doi":"10.2174/0115665240338945250317082242","DOIUrl":"https://doi.org/10.2174/0115665240338945250317082242","url":null,"abstract":"<p><strong>Background: </strong>The calcium-binding protein S100A12 plays a pivotal role in the progression of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). However, the underlying mechanisms are yet to be fully elucidated.</p><p><strong>Objective: </strong>This study aimed to investigate the role of S100A12 in LPS-induced injury of human pulmonary microvascular endothelial cells (HPMECs) and its molecular regulatory mechanism.</p><p><strong>Methods: </strong>An in vitro model of ALI/ARDS was established by lipopolysaccharide (LPS)-induced HPMECs. CCK-8, flow cytometry assay, and ELISA were used to detect the cell viability, apoptosis, and inflammation. The integrity of the endothelial barrier was assessed by tube formation assay and VE-cadherin and occludin protein levels. The molecular mechanism of S100A12 was analyzed by transcriptomics and validated using qRT-PCR and western blotting analyses.</p><p><strong>Results: </strong>S100A12 expression was significantly elevated in LPS-stimulated HPMECs, and S100A12 knockdown alleviated LPS-induced apoptosis, inflammation, and endothelial barrier dysfunction in HPMECs. Transcriptomic analysis revealed the potential gene network mapping regulated by LPS stimulation and S100A12 knockdown. Differentially expressed genes were significantly enriched in the JAK2/STAT3 signaling pathway as verified by western blotting analysis.</p><p><strong>Conclusion: </strong>Our results suggested S100A12 to be significantly upregulated in LPSinduced HPMECs; inhibiting S100A12 can alleviate endothelial cell barrier dysfunction through the JAK2/STAT3 signaling pathway and thereby improve LPS-induced HPMECs injury.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144062602","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":"Enhancement of Platinum-Based Drug Sensitivity in Ovarian Cancer Cells Through Hyperthermia-Induced Activation of the TGF-β1/β-Catenin Signaling Pathway.","authors":"Xiaogang Lv, Wenjuan Wu, Gaoting Huang, Xiaowen Yao, Shirong Zeng, Yifeng Wang","doi":"10.2174/0115665240367566250327040010","DOIUrl":"https://doi.org/10.2174/0115665240367566250327040010","url":null,"abstract":"<p><strong>Background: </strong>Platinum-based drugs like cisplatin are key in treating ovarian cancer, but resistance frequently leads to treatment failure. The TGF-β1/β- catenin signaling pathway has been implicated in tumor resistance. This study investigates whether hyperthermiaenhances ovarian cancer cell sensitivity to platinum-based drugs by activating the TGF-β1/β-catenin pathway.</p><p><strong>Methods: </strong>In vitro and in vivo models of ovarian cancer were treated with hyperthermia and cisplatin. Changes in TGF-β1 and β-catenin expression were measured using Western blotting, qPCR, immunohistochemistry, and cell viability assays to determine the impact of hyperthermia on drug sensitivity.</p><p><strong>Results: </strong>Hyperthermia significantly reduced TGF-β1 and β-catenin expression in ovarian cancer cells and tumor tissues, suppressing the pathway. This led to increased cisplatin sensitivity and higher apoptosis rates in vitro, while in vivo, tumor growth was significantly suppressed, and cisplatin's antitumor effects were enhanced.</p><p><strong>Conclusion: </strong>Hyperthermia boosts the effectiveness of platinum-based drugs in ovarian cancer by suppressing the TGF-β1/β-catenin pathway, presenting a potential strategy to overcome chemoresistance and improve patient outcomes.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802670","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":"Metabolomic Profiling Reveals Distinct Pathways in Degenerated and Non-Degenerated Rotator Cuff Tears: Implications for Pathogenesis and Treatment.","authors":"Furkan Bülbül, Emine Koç, Bilge Başak Fidan, Ozan Kaplan, Hasan Rüzgar, Onur Bilge, Mustafa Özer, Mustafa Çelebier, Feza Korkusuz","doi":"10.2174/0115665240364302250320025755","DOIUrl":"https://doi.org/10.2174/0115665240364302250320025755","url":null,"abstract":"<p><strong>Background: </strong>Tissue metabolomics is a promising technology for evaluating in situ changes in disease pathogenesis. It addresses a significant knowledge gap in the study of both degenerated and non-degenerated supraspinatus (SSp) tendons. This study analyzed the metabolomic profiles associated with rotator cuff tears (RCTs).</p><p><strong>Purpose: </strong>RCTs cause loss of function and shoulder pain, with the SSp muscle being the most frequently affected. Inflammation and complex metabolic changes may play roles in its etiology. Evaluation of the metabolomic differences between the degenerated and non-degenerated SSp tissues of RCT patients was aimed.</p><p><strong>Methods: </strong>A cross-sectional study of 14 patients with RCTs, diagnosed through physical examination and magnetic resonance imaging, was conducted. Degenerate and non-degenerate SSp tissue debris were collected during arthroscopy. Untargeted metabolomic analysis of these samples was performed using liquid chromatography quadrupole time-of-flight mass spectrometry (LC-Q-ToF-MS). Metabolic peaks were identified, matched, and normalized before further analysis. Partial least squaresdiscriminant analysis (PLS-DA), heatmap generation, unsupervised volcano plots, and fold-change analyses were conducted. A putative metabolite list was subsequently compiled to elucidate pathways of degeneration. These metabolites were matched with metabolic pathways using the RaMP-DB metabolite set library.</p><p><strong>Results: </strong>The tyrosine metabolism (p=4.93 x10-4), ferroptosis (p=1.25 x10-3), steroidogenesis (p=9.89 x10-4), and cholesterol biosynthesis (p=3.05 x10-3) were altered in the degenerated RCTs.</p><p><strong>Conclusion: </strong>These findings suggest that metabolomic alterations may be associated with the development of RCTs, with changes in tyrosine metabolism, ferroptosis, and lipid metabolism potentially contributing to muscle degeneration and inflammation. Identified disruptions in steroidogenesis provide new insights into the role of hormonal factors in RCT development. Understanding these metabolic pathways is clinically relevant in sports medicine, as it enables targeted therapies and personalized treatment strategies, ultimately enhancing recovery and improving outcomes for athletes.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802671","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":"Analysis of Alternative Splicing Events in Melanoma and their Implications for Prognosis.","authors":"Hongwei Deng, Xiang Huang, Ji Zhang, Xinyu Xu, Jianglin Wang, Li Liu, Yajun Yu, Jianguo Feng, Yijing He","doi":"10.2174/0115665240355992250311071633","DOIUrl":"https://doi.org/10.2174/0115665240355992250311071633","url":null,"abstract":"<p><strong>Introduction: </strong>Alternative splicing (AS) events significantly affect melanoma progression. Therefore, understanding their effect on prognosis is important for developing new treatments.</p><p><strong>Methods: </strong>Univariate Cox regression analysis and LASSO regression were carried out to identify key AS events, build an AS risk model, and classify sample risk levels. Pearson correlation analysis was also performed to analyze the relationship between AS events and RNA-binding protein (RBP) genes or indicators of immune infiltration. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using gene expression data from patients with varying risk levels. Univariate and multivariable Cox regression analyses were also carried out to examine the association between immune cell infiltration and prognosis.</p><p><strong>Results: </strong>A total of 41446 AS events were identified; among them, 446 AS events were identified as significantly associated with melanoma prognosis. An AS risk model for prognosis was established using seven key AS events. A close correlation was found between 137 AS events and 1037 RBP genes, suggesting that these genes may participate in the regulation of AS events. KEGG enrichment analysis revealed that the genes involved in AS were closely associated with immune system functions, which may explain why AS events affect the prognosis of melanoma. Finally, by combining the AS risk score and clinical indicators, we developed a nomogram model that could effectively predict melanoma prognosis.</p><p><strong>Conclusion: </strong>This analysis of AS events and regulation may aid in developing novel prognostic biomarkers and therapeutic targets for melanoma.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802656","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":"Bone Marrow Mesenchymal Stem Cell Senescence in the Development of Osteoporosis: Mechanisms, Interventions, and Future Directions.","authors":"Chengen Li, Bo Li, Jiuchao Zhang, Kun Liu, Gang Du, Cunliang Guo, Zhenguo Yang","doi":"10.2174/0115665240367456250323173450","DOIUrl":"https://doi.org/10.2174/0115665240367456250323173450","url":null,"abstract":"<p><p>Osteoporosis, a significant age-related disease, is marked by diminished bone density and an elevated risk of fractures, representing a considerable global health challenge. Bone marrow mesenchymal stem cells (BMSCs) are essential in maintaining bone integrity through their differentiation into osteoblasts, which are crucial for bone formation. Nevertheless, the aging of BMSCs diminishes their regenerative abilities and intensifies inflammation, thereby playing a critical role in osteoporosis pathogenesis. This review explores the intricate mechanisms of BMSC senescence and its influence on osteoporosis, detailing cellular and molecular markers, such as oxidative stress, the senescence-associated secretory phenotype (SASP), and pivotal signaling pathways, including P53, PI3K/mTOR, and autophagy. We assess current interventions aimed at reducing BMSC senescence, with an emphasis on pharmacological methods like melatonin and antioxidants, alongside nonpharmacological strategies, such as exercise and dietary supplementation with omega-3 fatty acids. Furthermore, the challenges and limitations of translating these strategies into clinical applications are addressed, highlighting the necessity for personalized medicine to accommodate treatment outcome variability. Future research directions should focus on emerging therapeutic targets and novel interventions, such as gene editing technologies and advanced tissue engineering techniques. By integrating these strategies, this review endeavors to enhance the understanding and treatment of osteoporosis, emphasizing the critical need to target BMSC senescence to develop effective therapies.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729156","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}