Connective Tissue Research最新文献

{"title":"Static magnetic fields promote osteogenesis via the lncRNA Gas5/miR-182/PKR molecular axis in rat osteoblasts and femoral defect models.","authors":"Jun Guo, Guangning Long, Fen Liu, Yifan Liu, Yunfei Luo, Pei Wang, Fei Tong","doi":"10.1080/03008207.2026.2667358","DOIUrl":"10.1080/03008207.2026.2667358","url":null,"abstract":"<p><strong>Purpose: </strong>Static magneticfields (SMF) stimulate osteogenesis, but the underlying mechanismremains unclear. This study investigated whether the lncRNAGas5/miR-182/PKR axis mediates SMF-enhanced osteogenic differentiation and bone repair.</p><p><strong>Materials and methods: </strong>Primary rat osteoblasts were induced with dexamethasone, ascorbic acid, and β-glycerolphosphate sodium, then exposed to 200 mT SMF or shamconditions. RT-PCR, Western blotting, ALP staining, alizarin redstaining, and dual-luciferase reporter assays were used to assessgene and protein expression, osteogenic markers, and lncRNAmiRNA binding. A femoral defect rat model was established, andtreated with SMF, lentiviral-mediated lncRNA Gas5 overexpression, or their combination. Bone formation was evaluated by Micro-CT, HE staining, and TRAP staining. Lentiviral vectors were used to over express lncRNA Gas5 in osteoblasts, and miR-182 mimicswere transfected to assess its role in osteogenesis.</p><p><strong>Results: </strong>SMF increased BMP2 expression, ALP activity, and calcification nodulesin osteoblasts, indicating enhanced osteogenic differentiation. SMF upregulated lncRNA Gas5 and PKR, while down regulating miR-182. Dual-luciferase assays confirmed lncRNA Gas5 spongesmiR-182, which directly targets PKR mRNA. LncRNA Gas5 over expression promoted osteogenic markers (BMP-2, Runx2, OSX, OCN) and mineralization, with SMF enhancing this effect synergistically. In femoral defect models, combined SMF and lncRNA Gas5 treatment increased bone formation, as shown by Micro-CT and histological analysis. miR-182 over expression suppressed osteogenic proteins, which was rescued by lncRNAGas5 co-expression, confirming its role as a negative regulatorin the axis.</p><p><strong>Conclusions: </strong>SMF promotes osteogenesis and bone defect repair via the lncRNA Gas5/miR-182/PKR ceRNA pathway, revealing a novel epigenetic mechanism and a promising noninvasive therapy strategy.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":" ","pages":"350-364"},"PeriodicalIF":1.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834720","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":"Targeting extracellular collagen assembly to enhance functional recovery in composite neuromuscular trauma.","authors":"Jolanta Fertala, Andrew Stolfe, Nikolas Guerriero, Andrew Zhou, Peter Beredjiklian, Alec Giakas, Mark L Wang, Michael Rivlin, Pedro K Beredjiklian, Andrzej Fertala","doi":"10.1080/03008207.2026.2693328","DOIUrl":"10.1080/03008207.2026.2693328","url":null,"abstract":"<p><strong>Purpose: </strong>Composite neuromuscular injuries involving damage to peripheral nerves and skeletal muscles result in poor functional recovery due to excessive scarring. Current therapies lack specificity or carry significant side effects. We investigated the efficacy of a recombinant anti-collagen antibody (ACA) designed to inhibit extracellular collagen fibril formation, thereby reducing scar formation without disrupting intracellular reparative pathways.</p><p><strong>Materials and methods: </strong>In a rabbit model of composite injury involving a peroneal nerve crush and volumetric muscle loss of the tibialis anterior muscle, animals received local injections of an ACA-loaded or control thermoresponsive hydrogel. We measured neuromuscular functional recovery after composite injury using biomechanical and electrophysiological assays. Tissue was analyzed using histology, immunohistochemistry, and Fourier transform infrared (FTIR) spectroscopy.</p><p><strong>Results: </strong>While electrophysiological parameters of injured nerves declined in all injured groups, ACA treatment markedly improved biomechanical properties of the injured limbs at 4 weeks post-injury compared to controls. This functional benefit was sexually dimorphic; females, who exhibited a more robust fibrotic response and severe muscle atrophy compared to males, demonstrated the most pronounced therapeutic recovery with ACA treatment. FTIR spectroscopy and polarized light microscopy confirmed that ACA treatment modulated the scar architecture, showing a trend toward reduced collagen content and cross-link maturity. Notably, the uninjured contralateral limbs likely exhibited compensatory hypertrophy and electrophysiological changes, highlighting their active role in systemic adaptation.</p><p><strong>Conclusions: </strong>Together, these findings suggest that targeting extracellular collagen fibrillogenesis may modestly enhance early functional recovery in composite neuromuscular trauma, particularly in biological contexts prone to excessive fibrosis.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":" ","pages":"425-446"},"PeriodicalIF":1.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148338150","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":"EZH2 depletion blocks the proliferation and collagen deposition of keloid fibroblasts via ferroptosis.","authors":"Hao Yang, Lei Zhang, Shuang Du, Jia He, Chuan Yang, Xing Chen","doi":"10.1080/03008207.2026.2665175","DOIUrl":"https://doi.org/10.1080/03008207.2026.2665175","url":null,"abstract":"<p><strong>Purpose: </strong>Benign fibroproliferative disorders known as keloids feature excessive fibroblast proliferation coupled with collagen accumulation, yet effective treatment remains lacking. Enhancer of zeste homolog 2 (EZH2) is involved in various skin diseases involving cell hyperproliferation; however, uncertainty persists regarding EZH2's specific role in driving keloid formation. Focusing on keloid pathogenesis, this research delineates EZH2-mediated proliferative mechanisms in keloid fibroblasts (KFs).</p><p><strong>Materials and methods: </strong>We examined EZH2 expression in KFs compared to normal human skin fibroblasts (HDFs). After knocking down EZH2 in KFs, CCK-8 assay for cell growth, along with EdU staining, and apoptosis was quantified through a combination of flow cytometry and Western blotting, migration was evaluated with a scratch assay, and matrix remodeling was analyzed through Western blot and immunofluorescence detection of collagen I/III, MMP-1/3, and α-SMA. Lipid ROS, thiobarbituric acid reactive substances (TBARS), and alongside quantification of core ferroptosis-associated mediators, with ferrostatin-1 (Fer-1) used for rescue experiments.</p><p><strong>Results: </strong>EZH2 expression was markedly elevated in KFs compared to HDFs. Knocking down EZH2 suppressed KF proliferation, migration, and collagen deposition, while promoting apoptosis and triggering ferroptosis, as indicated by increased lipid ROS and iron levels. Fer-1 treatment partially negated these outcomes, lessening the effects of EZH2 knockdown on fibroblast function and extracellular matrix dynamics.</p><p><strong>Conclusions: </strong>EZH2 is highly expressed in KFs and regulates KFs' hyperproliferation and collagen deposition partially through inhibiting ferroptosis, suggesting EZH2 as a potential therapeutic target for keloids.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":" ","pages":"1-12"},"PeriodicalIF":2.1,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834744","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":"Exosomal circZNF638 promotes postmenopausal osteoporosis progression through MGAT1-mediated SMAD9 glycosylation.","authors":"Yuxiao Luo, Yingjie Qi, Jian Li, Shangben Lin, Xin Fang","doi":"10.1080/03008207.2026.2626749","DOIUrl":"10.1080/03008207.2026.2626749","url":null,"abstract":"<p><strong>Purpose: </strong>This study aims to investigate the potential regulatory mechanism of circular RNA (circRNA) in postmenopausal osteoporosis (POMP). Understanding the molecular mechanism of POMP is crucial for developing effective therapeutic strategies.</p><p><strong>Materials and methods: </strong>A variety of bioinformatics tools were used to identify candidate circRNAs associated with POMP, and circZNF638 was selected as the target for further investigation. The circular structure of circZNF638 was confirmed through PCR-AGE assay and RNase R treatment. Additionally, exosome identification was performed in osteoclasts with and without circZNF638 overexpression to explore its role in intercellular communication. To assess osteoblast differentiation and mineralization under different experimental conditions, ALP activity detection, alizarin red staining, and Western blot were employed. The levels of N-glycosylation were also meticulously measured.</p><p><strong>Results: </strong>Following the confirmation of the circular structure of circZNF638, it was discovered that exosomal circZNF638 derived from osteoclasts significantly inhibited osteoblast differentiation and mineralization. Mechanistically, circZNF638 was found to recruit EWSR1 to upregulate MGAT1, mediating N-glycosylation of SMAD9, thereby inhibiting osteoblast differentiation and mineralization.</p><p><strong>Conclusions: </strong>The findings of this study indicate that exosomal circZNF638 derived from osteoclasts plays a pivotal role in promoting the progression of POMP through the MGAT1-mediated N-glycosylation of SMAD9. These insights provide a deeper understanding of the molecular mechanisms underlying POMP.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":" ","pages":"225-242"},"PeriodicalIF":1.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147303170","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":"Collagen I alleviates UVB-induced oxidative DNA damage and inhibits YAP-p73 apoptotic pathway in human keratinocytes HaCaT.","authors":"Yuying Zhu, Weiwei Liu, Tianyu Ji, Zhao San, Ruiyi Cao, Toshihiko Hayashi, Kazunori Mizuno, Shunji Hattori, Hitomi Fujisaki, Takashi Ikejima","doi":"10.1080/03008207.2026.2630869","DOIUrl":"10.1080/03008207.2026.2630869","url":null,"abstract":"<p><strong>Purpose: </strong>Ultraviolet B (UVB) irradiation is closely associated with human skin damage. Collagen I is found to be protective against UVB-caused apoptosis in human keratinocytes HaCaT, and in this study, we further investigated the potential underlying mechanisms.</p><p><strong>Materials and methods: </strong>Oxidative DNA damage was evaluated by assessing the DNA damage marker γ-H2AX, 8-OHdG, and reactive oxygen species (ROS). Relative cell numbers were determined by MTT assays, while apoptosis was evaluated by Hoechst 33,342 and Annexin V/PI double staining. Western blotting and RT-PCR were used to examine protein and mRNA expressions, respectively. Immunofluorescence confocal microscopy was used to visualize targeted proteins.</p><p><strong>Results: </strong>Collagen I inhibits DNA damage and oxidative stress in HaCaT cells exposed to UVB irradiation. The YAP-p73 complex responds to DNA damages caused by UVB irradiation, and leads to the transcription of pro-apoptotic genes, including <i>p21</i>, <i>PML</i> and <i>PUMA</i>. DNA damage enhances ROS production, which further oxidatively damages DNA, forming a positive feedback loop. The protective effects of collagen I depend on the ROS restriction. Mitophagy, the process specifically eliminates the damaged mitochondria which are the main sources of cellular ROS, is restored by collagen I, and this contributes to the decreased ROS production, and the subsequent attenuation of cell apoptosis after UVB irradiation.</p><p><strong>Conclusions: </strong>Collagen I-coating protects UVB-irradiated cells from YAP-p73 mediated apoptosis through restricting ROS production and thus alleviating DNA damages, owing to the restored mitophagy. Our study supports the clinical application of collagen products as anti-UVB agents.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":" ","pages":"243-257"},"PeriodicalIF":1.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146206789","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":"Elastic fiber-mediated hierarchical bundling of collagen fibers in subcutaneous fascia.","authors":"Kenshi Togashi, Tetsuo Sakamoto, Masaya Ikeda, Natsuki Maeda, Takafumi Watanabe, Naoki Takahashi, Yongchol Shin, Yasutada Imamura","doi":"10.1080/03008207.2026.2661977","DOIUrl":"10.1080/03008207.2026.2661977","url":null,"abstract":"<p><strong>Purpose: </strong>We aimed to clarify the localization and hierarchical structural roles of elastic fibers in subcutaneous fascia and to determine their contribution to the mechanical properties of this tissue.</p><p><strong>Materials and methods: </strong>Enzymatic digestion, calcein labeling, immunostaining of collagen and fibrillin-rich microfibrillar structures, scanning electron microscopy, immunogold SEM, and TOF-SIMS were performed to analyze the hierarchical fiber architecture of loose and dense regions of chicken subcutaneous fascia.</p><p><strong>Results: </strong>Both loose and dense regions exhibited hierarchical collagen fiber bundles associated with elastic fiber. In loose fascia, these structures were predominantly localized along the surface of flattened collagen bundles, whereas in dense fascia they were detected both on the surface and within the bundles, consistent with repeated hierarchical organization. Under the present experimental conditions, elastase treatment reproducibly altered bundle architecture and increased passive expansion behavior.</p><p><strong>Conclusions: </strong>These findings support a hierarchical organization of subcutaneous fascia in which fibrillin-rich microfibrillar structures are repeatedly arranged in association with collagen fiber bundles across multiple scales. Together, our results suggest a spatial model of fascial architecture that provides a structural basis for future functional investigations of fascial mechanics.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":" ","pages":"321-333"},"PeriodicalIF":1.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147764933","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":"Peptide p[63-82] induces transcriptomic alterations associated with processes involved in cartilage repair in osteoarthritic human chondrocytes.","authors":"Jessica S J Steijns, Guus G H van den Akker, Tim J M Welting, Marjolein M J Caron","doi":"10.1080/03008207.2026.2649000","DOIUrl":"10.1080/03008207.2026.2649000","url":null,"abstract":"<p><strong>Purpose: </strong>Osteoarthritis is a degenerative joint disease that can currently only be treated by alleviating pain or, ultimately, by a total joint replacement. The bone morphogenetic protein 7-derived peptide p[63-82] offers a potentially novel molecular treatment option for osteoarthritis. Mapping peptide-induced transcriptomic changes in human articular chondrocytes is expected to help reveal how p[63-82] confers its chondrocyte phenotype modulating bioactivity.</p><p><strong>Materials and methods: </strong>Human articular chondrocytes were isolated from the articular cartilage of patients with late-stage osteoarthritis undergoing total knee arthroplasty. Cells were stimulated with 100 nM p[63-82] peptide for 24 hours (or vehicle), after which RNA was isolated, and RNAseq was performed. Collagen type 6 levels were measured by immunoblotting, and extracellular matrix content was assessed by glycosaminoglycan measurement.</p><p><strong>Results: </strong>We found a total of 1976 differentially expressed genes. Reactome and GSEA pathway analyses highlighted pathways involved in Collagen Chain Trimerization and in the Assembly of Collagen Fibrils and Other Multimeric Structures. Indeed, expression analysis demonstrated the differential upregulation of COL4A2, COL6A2, COL9A3, COL16A1, and COL18A1 in the p[63-82] condition. The p[63-82] induced upregulation of COL6 gene expression was confirmed by immunoblotting. Furthermore, we observed a p[63-82]-induced increase in glycosaminoglycan content.</p><p><strong>Conclusions: </strong>The p[63-82] peptide induces profound transcriptomic changes in primary human articular chondrocytes. One of the dominant transcriptomic alterations was the differential expression of several collagen-related genes. Many of these collagen-related genes have established roles in cartilage homeostasis. The here-acquired transcriptomic insights provide clues into the therapeutic mechanisms of action of the p[63-82] peptide in human articular chondrocytes.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":" ","pages":"273-283"},"PeriodicalIF":1.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147627368","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":"SREBF2 drives osteoporosis by divergently regulating Hippo/YAP-mediated adipogenesis and BMP/Smad-mediated osteogenesis in bone marrow stromal cells.","authors":"Dawei Xiao, Yifei Li, Bo Liu, Dan Li, Hao Wu, Xiaofei Liu, Yunlei Zhai, Haiyang Yu","doi":"10.1080/03008207.2026.2650791","DOIUrl":"10.1080/03008207.2026.2650791","url":null,"abstract":"<p><strong>Purpose: </strong>Osteoporosis results from an imbalance in bone remodeling, often driven by the maldifferentiation of bone marrow stromal cells (BMSCs) toward adipogenesis rather than osteogenesis. Sterol regulatory element-binding transcription factor 2 (SREBF2) is a master regulator of cholesterol metabolism. Given the interplay between lipid metabolism and bone homeostasis, this study aimed to investigate the role of SREBF2 in regulating BMSC fate and to elucidate its underlying mechanisms in osteoporosis pathogenesis.</p><p><strong>Materials and methods: </strong>SREBF2 expression was analyzed via bioinformatics of osteoporosis datasets and validated in clinical samples. Its function was validated in vitro using shRNA knockdown in human BMSCs, assessing osteogenic (ALP, ARS staining) and adipogenic (Oil Red O staining) differentiation. Signaling mechanisms were explored using Western blot and rescue experiments with SIS3 (BMP inhibitor) and YAP overexpression. In vivo efficacy was evaluated in an ovariectomized (OVX) mouse model.</p><p><strong>Results: </strong>SREBF2 was significantly elevated in osteoporotic patients. Knockdown of SREBF2 in BMSCs enhanced osteogenesis and suppressed adipogenesis. Mechanistically, SREBF2 depletion inhibited Hippo signaling and activated BMP/Smad signaling. The pro-osteogenic effect was reversed by SIS3, while the anti-adipogenic effect was rescued by YAP overexpression. In vivo, SREBF2 knockdown ameliorated OVX-induced bone loss, improving microstructural parameters and restoring signaling balance.</p><p><strong>Conclusions: </strong>SREBF2 promotes osteoporosis by activating Hippo/YAP to drive adipogenesis while inhibiting BMP/Smad to suppress osteogenesis in BMSCs. Targeting SREBF2 is a promising therapeutic strategy.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":" ","pages":"284-296"},"PeriodicalIF":1.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147627349","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":"Rheological properties of the human and porcine oral mucosa.","authors":"Camille Déchelette, Guillaume Bouguéon, Adrien Naveau","doi":"10.1080/03008207.2026.2656203","DOIUrl":"10.1080/03008207.2026.2656203","url":null,"abstract":"<p><strong>Purpose: </strong>The objective of this study was to characterize the viscoelastic shear properties of gingival connective tissue under physiological conditions in humans and pigs. Porcine tissue is commonly used as a preclinical model due to its anatomical and mechanical similarity to human gingiva, which supports translational studies for gingival tissue engineering.</p><p><strong>Materials and methods: </strong>Human (<i>n</i> = 17) and porcine (<i>n</i> = 15) hard palate oral mucosa samples were subjected to histological characterization and shear rheological testing. Storage (G') and loss (G″) moduli were measured at 1 Hz for the epithelium, <i>lamina propria</i>, and whole mucosa in both species.</p><p><strong>Results: </strong>At 1 Hz, storage and loss moduli were within the same order of magnitude for human and porcine tissues across all analyzed layers. In human samples, mean storage modulus (G') values were 6.9 ± 2.3 kPa for the epithelium, 2.9 ± 0.5 kPa for the <i>lamina propria</i>, and 11.0 ± 7.1 kPa for the whole mucosa. Corresponding porcine values were 5.0 ± 2.0 kPa, 4.6 ± 3.9 kPa, and 7.6 ± 2.6 kPa, respectively. Overall, the viscoelastic response of palatal oral mucosa was comparable between species.</p><p><strong>Conclusions: </strong>The similar viscoelastic behavior observed in human and porcine gingival tissues supports the relevance of the porcine model for investigating gingival biomechanics. These findings provide quantitative shear modulus benchmarks that may inform the design and mechanical tuning of biomimetic scaffolds for gingival tissue engineering.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":" ","pages":"297-307"},"PeriodicalIF":1.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147627307","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":"5α-dihydrotestosterone upregulates interferon signaling and limits osteoclast differentiation during inflammatory state.","authors":"Kiana Chen, Michael Christof, Gulzada Kulzhanova, Chia-Lung Wu, Homaira Rahimi","doi":"10.1080/03008207.2026.2642775","DOIUrl":"10.1080/03008207.2026.2642775","url":null,"abstract":"<p><strong>Purpose: </strong>Rheumatoid arthritis is characterized by inflammatory erosions and increased prevalence in females. Androgen, the dominant sex hormone in males, is protective against bone loss. Here, we investigated the cellular targets of androgen and hypothesized that androgen negatively regulates TNFα-driven osteoclastogenesis.</p><p><strong>Materials and methods: </strong>Bone marrow-derived cells from a C57BL/6J mouse femur and tibia were plated with 10^-9M of 5α-dihydrotestosterone (DHT) or vehicle then collected for flow cytometry and flow sorting. Osteoclast precursors (OCPs), myeloid-like CD11b+Gr-1- cells, were grown to osteoclasts then fixed and TRAP-stained. Osteoclasts were quantified by cell counting. Single-cell RNA-sequencing was performed on DHT or vehicle-treated TNFα-stimulated cells, and the differences in cell populations, gene expression, gene ontology, and cell trajectory were analyzed via bioinformatic approaches. RT-qPCR validated sequencing results.</p><p><strong>Results: </strong>DHT-treated OCPs were decreased versus vehicle-treated OCPs (Vehicle = 12.43 ± 0.53%, DHT = 9.93 ± 0.85%, <i>p</i> < 0.05), and there was decreased differentiation from OCPs to osteoclasts (Vehicle = 403.3 ± 141.5, DHT = 10.67 ± 14.36, <i>p</i> < 0.01). Analysis identified osteoclastogenesis-related clusters that varied between samples and interferon-related processes upregulated with DHT treatment. Analysis also determined that DHT treatment may be associated with expression of the transcription factor Irf7. Isg15, the most differentially expressed gene in the DHT-treated clusters, may also be involved in osteoclastogenesis.</p><p><strong>Conclusions: </strong>In summary, androgen targets OCPs and limits their differentiation into osteoclasts. In myeloid populations, DHT treatment results in differential expression of interferon-related processes and genes and alters the trajectory of cells, potentially regulating osteoclastogenesis.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":" ","pages":"258-272"},"PeriodicalIF":1.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147467188","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}