Gene最新文献

{"title":"Exploring the relationship and diagnostic targets of seborrheic dermatitis and scalp psoriasis based on multi-omics integration analysis","authors":"Li Yang ,&nbsp;Yunying Wang ,&nbsp;Yiya Zhang ,&nbsp;Yisheng Cai ,&nbsp;Zhihua Fan ,&nbsp;Fangfen Liu","doi":"10.1016/j.gene.2025.149441","DOIUrl":"10.1016/j.gene.2025.149441","url":null,"abstract":"<div><div>Scalp seborrheic dermatitis (SD) and psoriasis (PSO) are prevalent chronic skin conditions with overlapping clinical manifestations, especially when confined to the scalp, which complicates differential diagnosis. This study integrates transcriptomic profiling and genetic association analyses to investigate potential causal links between SD and scalp PSO. Through RNA sequencing on lesional and non-lesional scalp samples from patients with SD and scalp PSO, as well as healthy controls, we found that seborrheic dermatitis may represent a risk factor for the progression to scalp PSO. Furthermore, TGM1 and IL36RN were identified as key potential molecular targets that could differentiate seborrheic dermatitis from scalp PSO.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"957 ","pages":"Article 149441"},"PeriodicalIF":2.6,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143787795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Major allelic variants in IRF6 and the association with Non-Syndromic orofacial Clefts: Insights from a Kerala-Based Case-Control study","authors":"Reema Rose Alappat ,&nbsp;Sunish Kadayil Sachith ,&nbsp;Puthucode V Narayanan ,&nbsp;Alex George","doi":"10.1016/j.gene.2025.149450","DOIUrl":"10.1016/j.gene.2025.149450","url":null,"abstract":"<div><div>Orofacial clefts, are among the most common congenital defects. Previous research has consistently shown that particular <em>IRF6</em> gene polymorphisms are related to nonsyndromic cleft lip with or without cleft palate (NSCL/P), which has been verified across many populations. This study aimed to investigate the role of specific <em>IRF6</em> polymorphisms in nonsyndromic orofacial clefts (NSOFC) within the Kerala population. A total of 100 NSOFC cases and matched controls were genotyped for five <em>IRF6</em> single nucleotide polymorphisms (SNPs): rs2235371, rs7552506, rs2235373, rs2235375, and rs2013162 using Next-Generation Sequencing. Statistical analyses (VassarStats, SNPstat, and MedCalc) and haplotype construction (Haploview) were performed to assess allelic, genotypic, and haplotype associations. Results showed that the major alleles (primarily “G” in four SNPs and “C” in rs2013162) were significantly more frequent in healthy controls, suggesting a protective effect. Conversely, minor alleles were overrepresented in NSOFC cases, indicating an elevated risk. Four SNPs (rs2235371, rs7552506, rs2235373, rs2235375) demonstrated robust protective effects under multiple inheritance models, while rs2013162 exhibited a less pronounced influence, displaying a notable protective effect only in the nonsyndromic cleft lip with palate (NSCLP) subgroup. Haplotype analysis identified G-C-G as consistently protective, whereas C-A-C and C-A-G conferred a higher risk for NSOFC. Overall, these findings underscore the importance of <em>IRF6</em> variants in NSOFC etiology and suggest that considering both individual SNPs and haplotypes can enhance understanding of orofacial cleft susceptibility. Further large-scale studies are recommended to validate these associations.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"955 ","pages":"Article 149450"},"PeriodicalIF":2.6,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143783773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"METTL3/IGF2BP3 mediates ORC6 via N6-methyladenosine modification to promote the progression of pancreatic ductal adenocarcinoma","authors":"Yang Shi ,&nbsp;Junwei Liu ,&nbsp;Qian Cheng ,&nbsp;Shuaihui Wu ,&nbsp;Wenjing Song ,&nbsp;Kunlei Wang ,&nbsp;Zhinan Chen ,&nbsp;Xinyin Li ,&nbsp;Qifeng Wei ,&nbsp;Dilinigeer Tayier ,&nbsp;Bo Liao ,&nbsp;Zhiyong Yang","doi":"10.1016/j.gene.2025.149468","DOIUrl":"10.1016/j.gene.2025.149468","url":null,"abstract":"<div><h3>Background</h3><div>Pancreatic ductal adenocarcinoma (PDAC) is recognized globally as one of the most lethal tumours, and effective biomarkers to diagnose PDAC early are needed. ORC6, a subunit of the origin recognition complex (ORC), initiates DNA replication and ensures genomic stability. Previous studies have indicated that ORC6 is procarcinogenic in various cancers, yet its role in PDAC remains uninvestigated.</div></div><div><h3>Methods</h3><div>We evaluated the relationships between ORC6 expression and the clinical features of patients with PDAC with the TCGA, GTEx, and GEO databases. The role of ORC6 in PDAC cells was explored by RNA interference <em>in vitro</em> and <em>in vivo</em>. Next, we verified the effect of the METTL3/IGF2BP3/ORC6 axis on PDAC progression by western blotting, RT-qPCR, RNA immunoprecipitation, and methylated RNA immunoprecipitation. Finally, transcriptome analysis was performed to explore the influence of ORC6 on p53 in PDAC cells.</div></div><div><h3>Results</h3><div>Elevated ORC6 levels were observed in PDAC cells, which correlated with poorer clinical outcomes. Both <em>in vivo</em> and <em>in vitro</em> experiments demonstrated that ORC6 knockdown suppressed proliferation and promoted apoptosis. Additionally, we demonstrated that METTL3/IGF2BP3 interacted with ORC6 mRNA via N6-methyladenosine modification to improve ORC6 mRNA stability. Transcriptomic analysis and experiments indicated that ORC6 promoted PDAC progression by inhibiting serine-15 phosphorylation in p53.</div></div><div><h3>Conclusion</h3><div>Our findings validate the role of ORC6 in PDAC and support the hypothesis that the METTL3/IGF2BP3/ORC6/p53 axis may be a novel therapeutic target for PDAC, and inhibiting this axis may be an advantageous therapeutic strategy for curing PDAC.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"955 ","pages":"Article 149468"},"PeriodicalIF":2.6,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143783772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficient transgenic system for the firebrat Thermobia domestica utilizing hyPBase and G0 founder prescreening","authors":"Kei Inada,&nbsp;Takahiro Ohde,&nbsp;Takaaki Daimon","doi":"10.1016/j.gene.2025.149449","DOIUrl":"10.1016/j.gene.2025.149449","url":null,"abstract":"<div><div>The firebrat, <em>Thermobia domestica</em>, is an apterygote model insect with favorable traits, including rapid generation turnover, high fecundity, and ease of laboratory rearing. We previously developed a method for embryo injection and CRISPR/Cas9-based genome editing in <em>Thermobia</em>. In the present study, we established a highly efficient transgenesis system using the hyperactive <em>piggyBac</em> transposase (hyPBase) to expand genetic manipulation techniques in <em>Thermobia</em>. By injecting embryos with a mixture of <em>hyPBase</em> mRNA and a donor plasmid expressing <em>GFP</em> under the control of an eye enhancer, we achieved the first successful transgenesis in <em>Thermobia</em>. Eye-specific GFP expression was observed in 5.7 % of G₀ individuals hatched from injected eggs. Notably, these GFP-positive G₀ founders exhibited significantly elevated germline transmission rates (53.3 %) compared with GFP-negative G₀ founders (19.0 %). Additionally, a significant difference in the proportion of G₁ transgenic progeny emerged between the GFP-positive and GFP-negative G₀ groups (20.0 % vs. 2.7 %), highlighting the utility of GFP expression as a predictor of transgenic G₁ offspring from injected G₀ founders. Furthermore, multiple transgene insertions mediated by hyPBase contributed to the increased transformation efficiency observed in G₀ founders with high transmission rates. Our findings offer valuable genetic toolkits for <em>Thermobia</em> that will facilitate advanced research on fundamental biological processes, such as the evolution of wings and metamorphosis.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"955 ","pages":"Article 149449"},"PeriodicalIF":2.6,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143760044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical and molecular assessment of a spastic ataxia 4 (SPAX4) patient with a novel variant in the MTPAP gene, and a systematic review","authors":"Moez Ravanbod ,&nbsp;Mahsa Mohammadi ,&nbsp;Parsa Soleimani ,&nbsp;Fariba Zemorshidi ,&nbsp;Shahriar Nafissi ,&nbsp;Afagh Alavi","doi":"10.1016/j.gene.2025.149463","DOIUrl":"10.1016/j.gene.2025.149463","url":null,"abstract":"<div><div>Spastic ataxia (SPAX) is a heterogeneous neurodegenerative disorder characterized by the simultaneous occurrence of spastic paraplegia and cerebellar ataxia, making the diagnosis and classification challenging. Genetically, SPAX is categorized into subtypes SPAX1-10. Mutations in the <em>MTPAP</em> gene lead to SPAX4 and some other neurological diseases. This gene encodes an enzyme with a key role in polyadenylation of mitochondrial mRNAs. Here, during whole-exome sequencing of an Iranian HSP cohort, we identified the first Iranian SPAX4 case, and fifth globally with a novel <em>MTPAP</em> variant. We also performed a systematic review based on the PRISMA 2020 guidelines to catalog all known <em>MTPAP</em> variants and assess the clinical and genetic profiles of all identified cases. A novel variant, c.1072C &gt; T in the <em>MTPAP</em> gene was identified and confirmed within the family using Sanger sequencing. The systematic review in four major databases for articles on <em>MTPAP</em> variants identified 12 <em>MTPAP</em> variants linked to various phenotypes. By comparing the obtained results, clinical and genetic heterogeneity was evident in the <em>MTPAP</em>-related disorders. Our findings significantly broaden the clinical and molecular landscape of <em>MTPAP</em>-related variants, extending beyond the confines of SPAX4.<!--> <!-->Due to the rarity of these diseases, considerable knowledge gaps persist regarding their underlying mechanisms and the implicated gene. Consequently, our research endeavors may facilitate the elucidation of pertinent biological pathways and the development of potential therapies.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"956 ","pages":"Article 149463"},"PeriodicalIF":2.6,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the clinical application and biological function of novel tsRNA tsRNA-Asp-5–0002 in hepatocellular carcinoma","authors":"Xinyue Ma ,&nbsp;Bairong Chen ,&nbsp;Yelan Tang ,&nbsp;Shaoqing Ju ,&nbsp;Rongrong Jing ,&nbsp;Wei Feng ,&nbsp;Wei Zong","doi":"10.1016/j.gene.2025.149459","DOIUrl":"10.1016/j.gene.2025.149459","url":null,"abstract":"<div><h3>Background</h3><div>Hepatocellular Carcinoma (HCC) is a highly fatal cancer, which is the most common malignant tumor globally. Recently, tRNA-derived small RNA (tsRNA) is a type of non-coding RNA that is closely related to various diseases. However, their precise existence and function in HCC remain unclear. We investigated the role of a novel tsRNA tsRNA-Asp-5–0002 in HCC.</div></div><div><h3>Methods</h3><div>We screened novel tsRNAs in the TCGA database. There are significant differences in tsRNA-Asp-5–0002 expression in HCC compared with other digestive system tumors. qRT-PCR was applied to confirm the level of tsRNA-Asp-5–0002 in 150 HCC patients, 50 patients with benign liver lesions, and 120 healthy controls. tsRNA-Asp-5–0002 mimics was constructed to transfect HCC cells and explore the effect of tsRNA-Asp-5–0002 on malignant phenotype of HCC. Bioinformatics analysis was used to predict the potential regulatory pathways of tsRNA-Asp-5–0002 in HCC.</div></div><div><h3>Results</h3><div>(1) tsRNA-Asp-5–0002 is down-regulated in HCC. (2) qRT-PCR detection tsRNA-Asp-5–0002 had high sensitivity and specificity. (3) Low-expressed tsRNA-Asp-5–0002 was related to TNM stage, differentiation, and LNM, and the ROC curve indicated that tsRNA-Asp-5–0002 had a better diagnostic performance for HCC. (4) tsRNA-Asp-5–0002 inhibits the proliferation and migration of HCC through the PLCB1/Wnt axis.</div></div><div><h3>Conclusions</h3><div>tsRNA-Asp-5–0002 can work as an auxiliary biomarker for HCC diagnosis. Over-expression of tsRNA-Asp-5–0002 restrains the malignant process of HCC, which may offer fresh tactics for the adjuvant treatment of HCC.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"956 ","pages":"Article 149459"},"PeriodicalIF":2.6,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Notch signaling and cancer: Insights into chemoresistance, immune evasion, and immunotherapy","authors":"Mohamed J. Saadh ,&nbsp;Thabit Moath Omar ,&nbsp;Suhas Ballal ,&nbsp;Morug Salih Mahdi ,&nbsp;Mamata Chahar ,&nbsp;Rajni Verma ,&nbsp;Rouaida Kadhim A_al-hussein ,&nbsp;Mohaned Adil ,&nbsp;Mahmood Jasem Jawad ,&nbsp;Ali M.A. AL-Nuaimi","doi":"10.1016/j.gene.2025.149461","DOIUrl":"10.1016/j.gene.2025.149461","url":null,"abstract":"<div><div>The Notch signaling pathway is a fundamental and highly conserved cell-to-cell communication system vital for embryonic development and tissue maintenance. However, its dysregulation has been associated with the initiation, progression, and chemoresistance of various cancers. In this comprehensive review, we will take an in-depth look at the multiple roles of the Notch family in cancer pathogenesis, immune response, and resistance to chemotherapy. We delve into the complicated mechanisms by which Notch signaling promotes tumor growth and development, including its influence on TME remodeling and immune evasion strategies. We will also be discussing recent studies that shed light on the connection between cancer stemness and chemoresistance mediated through the activation of Notch signaling pathways. Elucidation of the interplay between the Notch pathway and major constituents of the TME, including immune cells and cancer-associated fibroblasts, is necessary for the development of targeted therapies against Notch-driven tumors. We further discuss the potential of targeting Notch signaling alone or in combination with standard chemotherapy and immunotherapy as a potent strategy to overcome chemoresistance and improve patient outcomes. We conclude by discussing the challenges and future prospects of using Notch signaling as a therapeutic target in cancer treatment, focusing on how precision medicine and combination approaches are important.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"955 ","pages":"Article 149461"},"PeriodicalIF":2.6,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vitro investigation of epigenetic regulators related to chemo-resistance and stemness of CD133+VE cells sorted from U87MG cell line","authors":"Elham Abusharieh ,&nbsp;Nazneen Aslam ,&nbsp;Malek A. Zihlif ,&nbsp;Yasser Bustanji ,&nbsp;Suha Wehaibi ,&nbsp;Duaa Abuarqoub ,&nbsp;Diana Shahin ,&nbsp;Heba Saadeh ,&nbsp;Raghad Barham ,&nbsp;Abdalla S. Awidi","doi":"10.1016/j.gene.2025.149432","DOIUrl":"10.1016/j.gene.2025.149432","url":null,"abstract":"<div><div>Glioblastoma (GBM) is the most common and malignant adult primary brain tumor with frequent relapse and resistance to therapies. Glioma stem cells, a rare population, is thought to be the reason behind the treatment’s failure. It is imperative to investigate the disease mechanisms and identify the biomarkers by which glioma stem cells would contribute to treatment relapse and resistance to already available chemotherapeutic agents.</div><div>The <strong>CD133^+VE</strong> cells were isolated from U87MG cell line and characterized by morphological features, cell viability, self-renewal efficiency, migration potential and karyotyping. Doxorubicin Cisplatin, Irinotecan, Etoposide and Temozolomide were used to determine the anti-proliferative effect on <strong>CD133^+VE</strong> cells. Confocal microcopy was used to localize the chemotherapeutic agents in the <strong>CD133^+VE</strong> cells. In quest of epigenetic biomarkers, RNA sequencing was performed to find the role of lncRNAs in stemness and resistance to therapies. U87cell line and <strong>CD133^-VE</strong> cells were kept as controls for all the experiments.</div><div>It was found that <strong>CD133^+VE</strong>cells were highly proliferative with increased migration potential, elevated IC50 values against chemotherapeutic agents and showed distinct karyotyping related to pluripotency. Chemotherapeutic agent such as Doxorubicin was localized outside the nucleus revealing the drug resistance as evident by confocal microscopy. RNA sequencing revealed 126 differentially expressed lncRNAs (DELs) in <strong>CD133^+VE</strong>cells among which lncRNA LOXL1-AS1 was highly upregulated and lncRNA PAX8-AS1 was significantly downregulated. These lncRNAs has been reported to be related to drug resistance, migration and epithelial- to- mesenchymal transmission (EMT), self-renewal and stemness properties contributing to poor prognosis and disease relapse.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"956 ","pages":"Article 149432"},"PeriodicalIF":2.6,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The widespread misuse of StringTie’s gene identifier tags as de facto gene symbols does not allow consistent gene identification in published research","authors":"Liana Alves de Oliveira ,&nbsp;Gabriela Canalli Kretzschmar ,&nbsp;Sara Cristina Lobo-Alves ,&nbsp;Giovanna Nazaré De Barros Prezia ,&nbsp;Saloe Bispo ,&nbsp;Roberto Rosati","doi":"10.1016/j.gene.2025.149440","DOIUrl":"10.1016/j.gene.2025.149440","url":null,"abstract":"<div><div>Current RNA sequencing techniques allow the characterization of novel genes and transcript isoforms, with StringTie being an effective and widely used tool for transcript assembly. In merge mode, StringTie assigns identifiers to putative genes, prefixed with “MSTRG” by default. These tags are sometimes used by authors as the designated name for genes or transcripts of high relevance in their work, even though they are unique and unambiguous only within the context of one analysis. In addition, when such identifiers are used, detailed genomic information is essential to identify the genes of interest clearly. In this report, we examined 161 studies that referred to a gene or transcript by its StringTie identifier in their title or abstract. Of these, only 41% provided sufficient information to clearly identify the gene(s) of interest and allow the reproducibility of the results and their comparison to further independent research. In light of this, we offer recommendations to address this issue and improve reporting standards.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"954 ","pages":"Article 149440"},"PeriodicalIF":2.6,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143735239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TSH inhibits osteoclast differentiation through AMPK signaling pathway","authors":"Wenwen Zhang ,&nbsp;Yu Chen ,&nbsp;Yan Wang ,&nbsp;Yanman Zhou ,&nbsp;Honglin Guo ,&nbsp;Jin Xu","doi":"10.1016/j.gene.2025.149442","DOIUrl":"10.1016/j.gene.2025.149442","url":null,"abstract":"<div><h3>Purpose</h3><div>It is believed that osteoporosis (OP) is associated with hyperthyroidism as a result of the elevation in thyroxine levels. However, patients with subclinical hyperthyroidism, which is characterized by decreased levels of thyroid-stimulating hormone (TSH) alone, are at equal risk of osteoporosis. Research has shown that TSH receptor (TSHR) is expressed on osteoclasts, but whether TSH directly regulates osteoclasts and the underlying mechanisms remain unclear.</div></div><div><h3>Methods</h3><div>In this study, we used osteoclast precursor cell conditional TSHR-knockout (TSHR CKO) mouse to study the effects of TSHR knockout on bone metabolism in mice and the changes in osteoclast differentiation in vitro. Transcriptomics was used to identify differentially expressed genes and signaling pathways.</div></div><div><h3>Results</h3><div>In vitro, experiments confirmed that TSH inhibited osteoclast differentiation in mouse RAW264.7 monocyte/macrophage cell line and targeted the key signaling pathway AMPK by RNA-seq sequencing. We found TSHR CKO mice exhibited decreased femoral biomechanics and damaged bone microstructure. The serum levels of bone resorption marker were increased, accompanied by an increase in the number of osteoclasts.</div></div><div><h3>Conclusion</h3><div>TSH inhibits osteoclast differentiation by activating the AMPK signaling pathway, and exerts an osteoprotective effect. This study will provide guidance for the diagnosis and treatment of osteoporosis. TSH structural analogs or AMPK activators are expected to provide new ideas for the development of drugs to prevent and treat osteoporosis.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"955 ","pages":"Article 149442"},"PeriodicalIF":2.6,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143737987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}