FASEB bioAdvances最新文献

{"title":"Pulmonary Endothelial Extracellular Vesicles Preferentially Interact and Are Processed in Pulmonary Endothelial Cells","authors":"Aritra Bhadra,&nbsp;April Scruggs,&nbsp;April Haven,&nbsp;Morgan Malone,&nbsp;Natalie Bauer","doi":"10.1096/fba.2025-00327","DOIUrl":"10.1096/fba.2025-00327","url":null,"abstract":"<p>Extracellular vesicles (EVs) regulate vascular injury and homeostasis; however, the intracellular mechanisms for the EV effects are unknown. While EV components and functions are well studied, their cellular uptake and intracellular processing remain unclear. Following our previous work on EVs, we investigated EV uptake mechanisms and organelle localization. Pulmonary endothelial–derived EVs showed preferential interaction with pulmonary vessels, particularly injured vessels. Co-culture experiments confirmed endothelial cells as exclusive EV targets via energy-dependent, clathrin-mediated endocytosis. Intracellularly, EVs colocalized with lysosomes and trans-Golgi, suggesting degradation and protein recycling pathways. These findings provide insights into temporal EV uptake dynamics and organelle interactions, establishing a foundation for understanding EV processing and content distribution mechanisms.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"8 4","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13052107/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147632980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Simulated Microgravity Causes Faster Replication During Acute Infection of ME49-Toxoplasma Gondii and Alterations in Host Cells","authors":"Musfika Tasnim Shirin,&nbsp;Takafumi Yamada,&nbsp;Iqra Zafar,&nbsp;Daisuke Kondoh,&nbsp;Hiroki Bochimoto,&nbsp;Hironori Bando,&nbsp;Oluyomi Stephen Adeyemi,&nbsp;Yasuhiro Fukuda,&nbsp;Kentaro Kato","doi":"10.1096/fba.2025-00287","DOIUrl":"https://doi.org/10.1096/fba.2025-00287","url":null,"abstract":"<p>Spaceflight is important to explore the universe. However, astronauts face many health challenges in space including the increased risk of infection. During spaceflight, the microgravity weakens immunity, which causes opportunistic infections with pathogens such as herpesvirus. However, we have no information about the effects of microgravity on infections caused by other pathogens with a latent stage in their life cycle. In addition, there are no reports on host cell responses or the mechanisms that modulate changes under microgravity conditions. Due to the high cost and effort required for space study in actual microgravity, simulated microgravity plays an important role in mimicking conditions that allow researchers to study risks during spaceflights. <i>Toxoplasma gondii</i> is one of the top five important economic pathogens; it causes toxoplasmosis, may reactivate from the latent phase in immunocompromised individuals, and there is no active drug or vaccine. In this study, we observed the effect of simulated microgravity on <i>T. gondii</i> and on host cells. Simulated microgravity using a 3D clinostat induced host cell proliferation and caused aggregated cells to form three dimensional multicellular spheroids in Vero cells and HFF. Rapid egress and growth of tachyzoites during the acute phase of type II ME49 infection were observed under simulated microgravity.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"8 4","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://faseb.onlinelibrary.wiley.com/doi/epdf/10.1096/fba.2025-00287","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147715265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Temperature-Gradient Transcriptomic Atlas Reveals the PPAR Signaling Pathway Dysfunction in Heat Stroke Induced Liver Injury","authors":"Ying Zhu,&nbsp;Wanlin Liu,&nbsp;Chunyuan Yang,&nbsp;Teng Ma,&nbsp;Mingfei Han,&nbsp;Jinxu Zhang,&nbsp;Yunping Zhu,&nbsp;Jie Ma","doi":"10.1096/fba.2025-00308","DOIUrl":"https://doi.org/10.1096/fba.2025-00308","url":null,"abstract":"<p>Heat stroke (HS) is the most severe form of hyperthermia, with mortality exceeding 50% in severe cases. The liver is highly vulnerable to HS-induced injury, often triggering multi-organ failure. Although rapid cooling remains the primary treatment, the molecular mechanisms underlying hepatic damage remain elusive, highlighting an urgent need for mechanistic insights, especially given global extreme heat events. We established a HS model by gradually increasing the core temperature of mice from 40°C to 43°C. Mice were sacrificed at each target temperature to collect blood and liver tissues for hematological, biochemical, and histopathological analyses. Transcriptomic profiling was conducted on murine livers, and differentially expressed genes (DEGs) were identified and analyzed. The peroxisome proliferator-activated receptor (PPAR) signaling pathway was identified as a significantly enriched pathway and 12 key DEGs were validated by reverse transcription quantitative PCR (RT-qPCR) to assess temperature-dependent metabolic reprogramming. The expression of CD36, ACOX3, and PPARα was validated by immunohistochemistry at the protein level to investigate their response to heat stress. A graded murine HS model was established and histopathology analysis showed significant liver injury with core temperatures ≥ 42°C, manifesting as weight loss, elevated serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), neutrophilia, thrombocytopenia, hepatocyte necrosis, and sinusoidal congestion. Transcriptomic profiling revealed temperature-dependent DEGs from 41°C onward mainly involved in inflammatory/immune, lipid metabolism, apoptosis, and stress response pathways. DEGs consistently dysregulated across different temperatures were enriched in PPAR, insulin signaling, and endoplasmic reticulum (ER) stress-related pathways. RT-qPCR analysis revealed the altered expression of PPAR-related key genes, indicating functional disruption in lipid metabolism. Immunohistochemistry further confirmed these transcriptomic findings at the protein level, suggesting that heat stress induced reprogramming of the PPAR signaling pathway. Together, these findings suggest that HS-induced liver injury is closely associated with progressive metabolic reprogramming, with dysregulated lipid metabolism playing a central pathogenic role. By combining a murine stepwise HS model and transcriptomic analysis, we identified dysregulated PPAR signaling as a key temperature-dependent feature of liver injury, suggesting its potential role as a temperature-sensing node and therapeutic target. This work provides a framework with precise temporal windows and molecular candidates for the development of mechanism-directed intervention strategies for HS.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"8 3","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://faseb.onlinelibrary.wiley.com/doi/epdf/10.1096/fba.2025-00308","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147568924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Oxygen Equivalent of Lactate Accumulation and Sex: Similar Work–Lactate Slopes in Men and Women Regardless of Body or Fat-Free Mass Scaling","authors":"Benedikt Meixner,&nbsp;Mascha Lenk,&nbsp;Billy Sperlich","doi":"10.1096/fba.2025-00330","DOIUrl":"https://doi.org/10.1096/fba.2025-00330","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>The oxygen equivalent of blood lactate accumulation (ΔLa) is commonly expressed relative to body mass (BM), yet BM includes adipose tissue which does not substantially contribute to glycolytic energy production nor lactate distribution space and may confound sex comparisons. We examined whether replacing BM with fat-free mass (FFM) (i) improves the correspondence between calculated glycolytic work and 15-s sprint work and (ii) attenuates sex differences in the work–lactate relationship. Seventy-one trained cyclists (48 men, 23 women) performed a 15-s all-out seated cycling sprint on a Cyclus2 ergometer. Blood lactate was sampled at rest and repeatedly for 8 min post-sprint; ΔLa was defined as peak minus pre-exercise lactate. Glycolytic work (W_Gly) was calculated using an oxygen-equivalent approach with ΔLa scaled to either BM or FFM. General linear models included glycolytic work, sex, and 15-s work. Men exhibited higher 15-s work and ΔLa than women, but the slope of the relationship between W_Gly and 15-s work did not differ by sex for either BM or FFM. Regression models using FFM explained slightly more variance in 15-s work than BM (<i>R</i>² = 0.79 vs. 0.75). Adding sex improved model fit for both formulations (<i>R</i>² = 0.85 and 0.85, respectively), indicating primarily an intercept effect rather than a slope difference. Replacing BM with FFM provides only a small improvement in explaining 15-s work and does not reveal sex-specific differences in the work–lactate slope. Thus, the lactate oxygen equivalent appears sex-invariant while FFM-based scaling may still be preferred for a more physiologically grounded estimate of W_Gly.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"8 3","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://faseb.onlinelibrary.wiley.com/doi/epdf/10.1096/fba.2025-00330","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147566579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma Proteomic Signatures of Pediatric Sepsis Reveal Persistent Inflammation and Phase-Specific Biomarkers","authors":"Fahd Alhamdan,&nbsp;Yi-Cheng Sin,&nbsp;Erik Malm,&nbsp;Hanna Van Pelt,&nbsp;Samuel Kim,&nbsp;LeeAnn Higgins,&nbsp;Yue Chen,&nbsp;Koichi Yuki","doi":"10.1096/fba.2026-00006","DOIUrl":"10.1096/fba.2026-00006","url":null,"abstract":"<p>Sepsis remains a leading cause of pediatric morbidity and mortality, yet its molecular underpinnings are poorly understood. Here, we performed mass spectrometry–based plasma proteomics and cytokine profiling in pediatric sepsis patients at the acute phase (AP) and recovery phase (RP), alongside preoperative surgical controls. In AP vs. control, we identified 41 differentially abundant (DA) proteins, including acute-phase reactants and complement factors, with persistent but attenuated expression in RP. Pathway analysis revealed sustained enrichment in inflammatory and complement activation processes during both AP and RP, with partial restoration of immune surveillance and vascular homeostasis in recovery. Machine learning highlighted complement components (C9, C1R) and LRG1 as candidate AP biomarkers, and S100A9 as an RP-associated marker. Comparative analysis with adult sepsis proteomes uncovered age-specific complement activation patterns: adults displayed higher classical pathway activity, whereas pediatric patients exhibited enhanced alternative pathway activity. Cytokine profiling confirmed sustained immune activation and endothelial perturbation across sepsis phases. We also compared the sepsis cohort with the sterile inflammation (SI) cohort, which revealed distinct adaptive immune enrichment in sepsis while innate immune predominance in SI, enabling the identification of potential sepsis-specific protein signatures. Together, these findings delineate the dynamic immune and vascular proteomic landscape of pediatric sepsis, reveal biomarkers distinguishing sepsis from sterile inflammation, and highlight age-related complement pathway differences with potential therapeutic implications.</p><p><b>Trial Registration:</b> ClinicalTrials.gov: NCT04103268, NCT04299828</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"8 3","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12972194/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147431672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mapping Intestinal Paracellular Perm Eability in Mice: Regional and Cellular Variability Under Physiological and Stimulated Conditions","authors":"Mathilde Miquel,&nbsp;Kadirey Verwaerde,&nbsp;Anissa Edir-Kibri,&nbsp;Mikael Albin,&nbsp;Florence Blas-Y-Estrada,&nbsp;Audrey Samper,&nbsp;Elodie Rousseau-Bacquie,&nbsp;Hervé Robert,&nbsp;Hélène Eutamène,&nbsp;Vassilia Théodorou,&nbsp;Christine Coméra","doi":"10.1096/fba.2025-00325","DOIUrl":"10.1096/fba.2025-00325","url":null,"abstract":"<p>Intestinal paracellular permeability was analyzed ex vivo by incubation of tissue segments at 0°C with the fluorescent dyes FM1-43FX (FM) or TRITC-dextran 3 kDa lysine-fixable (TD3L) and confocal microscopy in (i) healthy mice and (ii) mice submitted to chronic stress or lipid diets. In the small intestine of healthy mice, FM staining was restricted to the apical surface of enterocytes but fully penetrated around Goblet cells, enteroendocrine cells, tuft cells, and apoptotic cells. The same cell types were similarly labeled in the colon when located on the tissue surface but not within the crypts. TD3L exhibited a comparable labeling pattern but also showed moderate staining of the basolateral surface of enterocytes at the tips of small intestinal villi, and also substantial penetration around colonic epithelial cells at the surface or top of crypts. The study reveals patterns of permeability likely corresponding to the “leak” pathway of paracellular transport through the intestinal epithelium, because transcellular endocytosis is blocked at 0°C. This pathway is found around specific cell populations involved in the luminal detection of food, antigens, microbes, or their secretions. These trigger immune, neural, and tissue responses that maintain intestinal homeostasis. Chronic stress induced by glucocorticoid exposure increased FITC-dextran 4 kDa permeability in vivo. Using FM, increased paracellular permeability was also detected ex vivo and selectively localized in the colon of stressed mice. A single oral administration of a lipid-rich food also increased ex vivo permeability around jejunal enterocytes. Pathophysiological increases in paracellular permeability are therefore detectable using the FM methodology.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"8 3","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12963463/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147376484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Boosting Cuproptosis in Breast Cancer Therapy via Photodynamic Treatment With a New Liposome","authors":"Jie Yu,&nbsp;Ning Sun,&nbsp;Limei You,&nbsp;Jialing Liu,&nbsp;Mengna Niu,&nbsp;Jiacheng Shi,&nbsp;Weixin Chen,&nbsp;Futong Li,&nbsp;Shengbao Wang,&nbsp;Jiaqi Liu","doi":"10.1096/fba.2025-00280","DOIUrl":"10.1096/fba.2025-00280","url":null,"abstract":"<p>Breast cancer (BC) is one of the most common cancers in women around the world, and utilizing a combined approach is a crucial strategy. Induction of cuproptosis in tumor cells is a novel antitumor approach, though its standalone efficacy remains unclear. In this study, we prepared a novel liposome loaded with the photosensitizer indocyanine Green (ICG) and the cuproptosis inducer elesclomol-Cu (ES-Cu) to examine the synergistic effects of photodynamic-cuproptosis treatment on BC. The cuproptosis inducer ES-Cu and the photosensitizer ICG were encapsulated in nanoliposomes with a membrane hydration approach and then validated in vitro and in vivo. JC-1, MDA, GSH, and other cuproptosis-related indicators were used to confirm the ability of PDT to enhance ES-Cu-induced cuproptosis in MCF-7 breast cancer cells. For confirming the cytotoxic impact of PDT in conjunction with the cuproptosis inducer, tests for CCK-8 and cell death staining were performed. The drugs were administered to animals via tail vein injection to observe their tumor inhibition effects in vivo. Their safety was assessed by monitoring changes in body weight. The average particle size of liposomes loaded with ES-Cu and ICG was 208.3 ± 1.07 nm, exhibiting a consistent nanospherical morphology. ICG produced cytotoxic reactive oxygen species (ROS) that enhanced ES-Cu-induced cell cupping under NIR laser irradiation. The therapeutic effect of the synergistic treatment combining PDT and cuproptosis was validated in both in vitro and in vivo experiments. This investigation proved that PDT markedly augments the ES-Cu-induced cuproptosis in breast cancer cells, demonstrating a synergistic therapeutic effect. This synergistic effect presents a novel therapy approach for BC with substantial practical application potential.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"8 2","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12913696/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146225899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to “Interoceptive Information of Physical Vigor Through Circulating Insulin-Like Growth Factor 1”","authors":"","doi":"10.1096/fba.2026-00036","DOIUrl":"10.1096/fba.2026-00036","url":null,"abstract":"<p>J. A. Zegarra-Valdivia, M. Z. Khan, J. Fernandes, et al., “Interoceptive Information of Physical Vigor Through Circulating Insulin-Like Growth Factor 1,” <i>FASEB BioAdvances</i> 8, no. 1 (2026): e70084, https://doi.org/10.1096/fba.2025-00226.</p><p>In the original paper, the name of one of the authors was incorrect. It was incorrectly stated as “M. Zahid Kahn.” The author's correct name is “M. Zahid Khan.”</p><p>Additionally, in the original paper, Supplementary Figures: S1B, S2B, S2D, S3, S4B, S4D, S4E, S5A, S5B, S5C, S5E, and S6D contained blank panels. The correct graphical data that were peer reviewed have been returned to the supplementary figures.</p><p>We apologize for these errors.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"8 2","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12892122/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146178556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circadian Reprogramming of Protein Homeostasis and Glycolipid Metabolism in Diabetic Nephropathy","authors":"Xiao-Qian Li,&nbsp;Lei Cheng,&nbsp;Tian-Fen Chen,&nbsp;Yi-Nuo Ma,&nbsp;Lu-Yao Wang,&nbsp;Xiao-Hui Li,&nbsp;Ting-Yu Fu,&nbsp;Jing Xiao,&nbsp;Zhan-Zheng Zhao","doi":"10.1096/fba.2025-00305","DOIUrl":"10.1096/fba.2025-00305","url":null,"abstract":"<p>Dysfunction of the circadian clock has been implicated in the pathogenesis of various diseases, including metabolic disorders, inflammatory conditions, and cancer. While the significance of circadian rhythm in diabetic nephropathy is gaining attention, the specific alterations in circadian profiles in diabetic nephropathy remain unexplored. In the present study, we performed RNA sequencing on renal cortex samples collected every 4 h across the day from both control and diabetic mice. The rhythmicity of genes was identified using the JTK_CYCLE algorithm for each group. Genes that lost, acquired, or sustained rhythmicity in diabetic mice were denoted the circadian dysregulation gene set. Subsequent bioinformatic analyses focused on this gene set to investigate the circadian reprogramming in diabetic nephropathy. We observed significant circadian disruption in the kidney of diabetic mice, marked by both the gain and loss of rhythmicity, along with alterations in the phase and relative amplitude of genes that retained rhythmic expressions. Circadian disturbances, such as phase shifts and alterations in relative amplitude or mesor, were also noted in core clock genes. Furthermore, genes that lost rhythmicity in diabetic nephropathy were predominantly associated with protein homeostasis and glycolipid metabolism, whereas those that gained rhythmicity were mainly linked to gene regulation, fatty acid metabolism, and protein transport. The genes in the circadian dysregulation gene set that exhibit differential expression at least at one Zeitgeber time were most prominently enriched in the lipid metabolic process. WGCNA and correlation analysis revealed co-expression networks involving core clock genes and PPAR signaling pathway with renal triglyceride levels. Our study reveals substantial circadian disruption in diabetic nephropathy, with significant impacts on protein homeostasis and glycolipid metabolism. Furthermore, our findings highlight the potential influence of circadian system dysregulation on the disorder of fatty acid metabolism in diabetic nephropathy.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"8 2","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12892125/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146178583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Scientific Case for Animal Models: A Perspective From Musculoskeletal Researchers","authors":"Michael Hadjiargyrou,&nbsp;Blake E. Hildreth III,&nbsp;Frank Ko,&nbsp;Uma Sankar,&nbsp;Tao Yang","doi":"10.1096/fba.2025-00313","DOIUrl":"10.1096/fba.2025-00313","url":null,"abstract":"<p>The National Institutes of Health (NIH) has launched a major initiative to expand human-based New Approach Methodologies (NAMs) in biomedical research and reduce reliance on animal models. While NAMs offer powerful complementary tools, animal-based research remains indispensable in musculoskeletal science for understanding complex cellular and systemic processes, disease onset and progression, and developing effective therapies. Foundational knowledge of embryonic development, disease mechanisms, tissue regeneration, gene function, and systemic pharmacology has emerged from animal models and will continue to do so. This review underscores the essential role of animal models in five key areas of musculoskeletal biology: osteoporosis, osteoarthritis, bone fracture repair and regeneration, bone cancer, and Inherited Skeletal Disorders (ISDs). We also examine NAMs including organoids, engineered scaffolds, organ-on-chip platforms, and Artificial Intelligence (AI)/computational modeling, highlighting their strengths in mechanistic and high-throughput studies but also their limitations in replicating in vivo structural, physiological, biomechanical, and systemic complexity. Animal models remain the gold standard for exploring disease mechanisms, testing preclinical therapeutic and diagnostic efficacy and safety, and translating discoveries into clinical practice. Rather than replacing animal research, NAMs should be integrated as complementary approaches to advance understanding and innovation. Curtailing animal research would jeopardize medical progress and hinder life-saving interventions for humans and animals alike. This review aims to inform the public and policymakers on the continued necessity of ethically conducted animal research as a cornerstone of musculoskeletal health.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"8 2","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12885169/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146156336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}