Connective Tissue Research最新文献

{"title":"Transcriptomic comparison of the infrapatellar fat pad between young patients with traumatic knee injury and older patients with knee osteoarthritis.","authors":"Tao Li, Pan Wang, Chun Li, Yifan Chen","doi":"10.1080/03008207.2026.2712531","DOIUrl":"10.1080/03008207.2026.2712531","url":null,"abstract":"<p><strong>Purpose: </strong>The infrapatellar fat pad (IFP) is increasingly recognized as an active contributor to knee osteoarthritis (KOA) pathogenesis. However, age-related transcriptional changes in the IFP remain poorly understood, and whether observed differences are purely age-dependent or confounded by disease status is unclear. This study aimed to compare transcriptomic profiles of the IFP between young patients with traumatic knee injury and older patients with KOA.</p><p><strong>Methods: </strong>IFP samples were obtained from three young trauma patients (21-28 years, KL grade 0) and three older patients with KOA (64-72 years, KL grade III-IV). Bulk RNA sequencing was performed to compare transcriptomes between groups. Differential expression was analyzed with DESeq2 (|log2FC| ≥1, unadjusted <i>p</i> < 0.05), followed by GO and KEGG pathway enrichment. Real-time PCR confirmed key expression changes.</p><p><strong>Results: </strong>Compared with the young trauma group, the old KOA group exhibited 247 upregulated (<i>CSN1S1</i>, <i>SCN9A</i>, <i>P2RY14</i>, <i>EIF3C</i>, etc) and 334 downregulated genes (<i>PI15</i>, <i>WISP3</i>, <i>DMKN</i>, <i>NUTM2G</i>, etc). The old KOA group exhibited significantly reduced expression of extracellular matrix (ECM) genes, including <i>COL1A1</i>, <i>COL2A1</i>, and <i>FN1</i>. Additionally, core genes of the PI3K-Akt signaling pathway, such as <i>AKT1</i>, <i>ITGA2B</i>, and <i>MYB</i>, were also downregulated in the old KOA group.</p><p><strong>Conclusions: </strong>The IFP in old KOA exhibits a transcriptomic profile characterized by dampened ECM structural gene expression and suppressed PI3K-Akt signaling compared with young trauma patients. While confounded by injury status, these findings suggest that age-related loss of ECM integrity may contribute to IFP dysfunction in established KOA and warrant validation in healthy aging cohorts.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":" ","pages":"568-582"},"PeriodicalIF":1.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148676878","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":"Combination ex vivo regional gene therapy with sonic hedgehog and bone morphogenetic protein-2 does not enhance bone healing in critical size defects.","authors":"Cory K Mayfield, Julian Wier, Jacob R Ball, Matthew C Gallo, Fergui Hernandez, Tara Shelby, Elizabeth Lechtholz-Zey, Sarah Bergren, Hannah Shelby, Amy Tang, Osamu Sugiyama, Jay R Lieberman","doi":"10.1080/03008207.2026.2697221","DOIUrl":"10.1080/03008207.2026.2697221","url":null,"abstract":"<p><strong>Purpose: </strong>Large bone defects pose significant challenges for orthopedic surgeons. Regional gene therapy using adipose-derived stem cells (ADSCs) transduced with a lentiviral vector to express bone morphogenetic protein 2 (LV-BMP-2) has shown promise in preclinical models. Recent studies suggest sonic hedgehog (SHH)-mediated signaling may act synergistically with BMP-2 to enhance osteogenesis. This study evaluated whether combination gene therapy with rat ADSCs transduced with LV-BMP-2 and LV-SHH could heal rat critical size femoral defects.</p><p><strong>Methods: </strong>Seventy-one rats were randomly assigned to seven groups including four experimental groups, one positive control, and two negative controls. A two-step transcription amplification (TSTA) lentiviral vector was used to transduce BMP-2 and/or SHH into ADSCs. A 6 mm critical-sized femoral defect was created in Lewis rats and experimental groups received transduced cells. Biomechanical, imaging, and histomorphometric analysis was conducted to evaluate bone healing outcomes.</p><p><strong>Results: </strong>No significant difference in mean stiffness, total energy to failure, or maximum torque was observed between rats receiving 3 M LV-BMP-2 versus those receiving combination therapy of 3 M or 5 M LV-BMP-2 + LV-SHH therapy, however all had superior healing compared to negative controls. Similar results were observed for imaging and histomorphometric outcomes.</p><p><strong>Conclusions: </strong>These results demonstrate that combination gene therapy with LV-BMP-2+LV-SHH results in equivalent healing when compared to BMP-2 therapy at the same cell dose, demonstrating that SHH does not enhance osteoinductive signaling <i>in vivo</i> when using this therapeutic strategy. These findings suggest that the regenerative capacity of regional LV-BMP-2 gene therapy may exceed the window in which SHH can provide incremental biological benefit.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":" ","pages":"467-479"},"PeriodicalIF":1.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148429953","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":"Mechanotransduction in musculoskeletal mesenchymal tissues: implications for bone, tendon, and cartilage regenerative engineering-a narrative review.","authors":"Nahum Rosenberg","doi":"10.1080/03008207.2026.2729285","DOIUrl":"10.1080/03008207.2026.2729285","url":null,"abstract":"<p><strong>Purpose: </strong>To integrate evidence on how mechanical signals regulate musculoskeletal connective-tissue biology and how cellular context and loading history shape mechanotransduction and mechanical memory.</p><p><strong>Methods: </strong>This narrative review synthesized PubMed-indexed evidence on extracellular matrix mechanics, adhesion complexes, the cytoskeleton, nucleus, primary cilia, mechanosensitive ion channels, cell state, and loading history in bone, tendon, ligament, and cartilage.</p><p><strong>Results: </strong>Mechanotransduction is best understood as a coupled extracellular matrix-integrin-cytoskeleton-nucleus continuum rather than as independent cytoskeletal or nuclear drivers. Responses are conditioned by lineage stage, anatomic niche, inflammation, cellular subpopulation, and prior mechanical exposure. Mechanical memory may be encoded through persistent YAP/TAZ activity, microRNA programs, DNA methylation, histone modifications, chromatin architecture, and metabolic remodeling. Evidence is strongest for bone, including Piezo-dependent osteogenesis, TRPV4-mediated shear sensing, viscoelastic compression, osteocyte-stromal extracellular-vesicle signaling, and osteogenesis-angiogenesis coupling. Tendon and ligament require anisotropic architecture and strain-window control, whereas cartilage shows a narrow distinction between physiologic TRPV4-associated anabolism and high-strain or inflammation-sensitized Piezo/YAP-mediated maladaptation.</p><p><strong>Conclusions: </strong>Translational implications include mechanically defined cell expansion, biomaterial preconditioning, stage-specific rehabilitation, and potency assays incorporating loading history. Direct clinical validation of stable perioperative cellular mechanical memory remains limited. Future studies should combine controlled mechanical perturbation with bulk and single-cell RNA sequencing, chromatin-accessibility profiling, spatial methods, and perturbational genomics.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":" ","pages":"628-641"},"PeriodicalIF":1.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148910952","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":"Kaempferol binds with NSUN2 to mediate RNA 5-methylcytosine modification of BMP2 in osteogenic differentiation.","authors":"Nan Yu, Guanyi He, Rui Huang, Yingzhe Jin, Ming Yao, Huibin Zhang, Rui Zhu","doi":"10.1080/03008207.2026.2669838","DOIUrl":"10.1080/03008207.2026.2669838","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to investigate the effects and underlying mechanism of kaempferol (Kae) on osteogenic differentiation through 5-methylcytosine (m5C) modification in bone metabolism.</p><p><strong>Materials and methods: </strong>Dexamethasone (DEX, 1 μM) was used to inhibit the differentiation of MC3T3-E1 cells to mimic osteoporosis <i>in vitro</i>. The effects of Kae (5, 10, and 20 μM) on osteogenic differentiation were evaluated. m5C levels in MC3T3-E1 cells were measured by m5C dot blot assay, and the expression of several m5C-related genes was detected. The binding between Kae and an m5C-related gene was examined, and the interaction between NSUN2 andBMP2 was assessed. To investigate the regulatory role of Kae in osteoporosis, an ovariectomy (OVX)-induced osteoporotic mouse model was established.</p><p><strong>Results: </strong>Kae at 5-20 μM promoted osteogenic differentiation of MC3T3-E1 cells. Kae treatment increased m5C levels and NSUN2 expression in MC3T3-E1 cells. Kae bound to NSUN2, and inhibition of NSUN2 partially attenuated the pro-osteogenic effects of Kae. Furthermore, NSUN2 inhibition promoted BMP2 mRNA degradation. Inhibition of BMP2 significantly reversed the effect of NSUN2 overexpression on osteogenic differentiation. <i>In vivo</i>, Kae alleviated OVX-induced osteoporosis by reducing bone loss.</p><p><strong>Conclusions: </strong>Kae promotes osteogenic differentiation of osteoblasts <i>in vitro</i> and ameliorates bone loss in OVX-induced osteoporotic mice. Kae binds to NSUN2 to mediate RNA m5C modification of BMP2 during osteogenic differentiation. Kae may be a promising therapeutic agent for osteoporosis.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":" ","pages":"377-392"},"PeriodicalIF":1.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147866703","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":"Investigating the genetic basis of fibrotic pathway dysregulation in Dupuytren's contracture.","authors":"Alvita Vilkeviciute-Petraite, Dovile Basalykiene, Migdolija Baltakyte, Edita Kunceviciene, Enrika Pileckaite, Gediminas Samulenas, Alina Smalinskiene","doi":"10.1080/03008207.2026.2680153","DOIUrl":"10.1080/03008207.2026.2680153","url":null,"abstract":"<p><strong>Purpose: </strong>Dupuytren's contracture (DC) is a common fibroproliferative disorder with strong genetic predisposition. This study aimed to investigate the association between genetic variants in key fibrotic pathways and DC susceptibility in a Lithuanian population.</p><p><strong>Materials and methods: </strong>We conducted a case-control study including 116 patients with DC and 103 healthy controls. Genotyping of four single nucleotide polymorphisms (SNPs) involved in fibrotic pathway regulation was performed: <i>COL1A1</i> rs1800012, <i>TAB2</i> rs2179367, <i>SFRP4</i> rs1668357, and <i>SFRP4</i> rs1668347.</p><p><strong>Results: </strong>The <i>COL1A1</i> rs1800012 A allele demonstrated a significant protective effect against DC (OR = 0.584; 95% CI: 0.350-0.973; <i>p</i> = 0.039), with the strongest association observed in the dominant model (CA + AA <i>vs</i>. CC: OR = 0.521; 95% CI: 0.286-0.951; <i>p</i> = 0.034). Conversely, the <i>SFRP4</i> rs1668347 C allele was associated with increased DC risk (OR = 1.831; 95% CI: 1.126-2.976; <i>p</i> = 0.015), with significant associations in codominant (AC <i>vs</i>. AA: OR = 2.203; <i>p</i> = 0.007), dominant (AC + CC <i>vs</i>. AA: OR = 2.162; <i>p</i> = 0.007), and overdominant (AC <i>vs</i>. AA + CC: OR = 2.105; <i>p</i> = 0.010) models. No significant associations were found for the other investigated SNPs.</p><p><strong>Conclusions: </strong>Our findings support the involvement of collagen metabolism and Wnt signaling in DC pathogenesis. The protective effect of <i>COL1A1</i> rs1800012 and the risk-enhancing effect of <i>SFRP4</i> rs1668347 provide additional insights into the genetic basis of DC and may contribute to the development of predictive tools and targeted therapies for this debilitating condition.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":" ","pages":"393-402"},"PeriodicalIF":1.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148136782","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":"Ozonated water attenuates nucleus pulposus cell apoptosis and matrix degradation by suppressing NF-κB signaling in a rat model of <i>Staphylococcus aureus</i>-induced discitis.","authors":"Yang Luo, Pengfei Li, Guangshen Li, Yang Li, Siqi Ma, Chunmao Chen, You Li, Haijun Li","doi":"10.1080/03008207.2026.2688122","DOIUrl":"10.1080/03008207.2026.2688122","url":null,"abstract":"<p><strong>Purpose: </strong>Discitis is a severe suppurative infection of the intervertebral disc (IVD) posing significant clinical challenges. This study evaluated the therapeutic efficacy of ozonated water (OW) in a rat model of <i>Staphylococcus aureus</i>-induced discitis and elucidated its underlying mechanisms, focusing on NF-κB signaling, extracellular matrix homeostasis, and nucleus pulposus (NP) cell apoptosis.</p><p><strong>Methods: </strong>A rat tail coccygeal IVD discitis model was established by injecting <i>S. aureus</i> (10² cfu) into the disc space. From day 3 post-infection, animals received transdiscal lavage with normal saline, levofloxacin (5 mg/mL), or OW (30 μg/mL) three times daily until day 9. In vitro, NP cells were stimulated with S. aureus Protein A (SpA, 1 μg/mL). Antibacterial activity, extracellular matrix metabolism, inflammatory cytokine expression, NF-κB p65 signaling, and apoptosis were evaluated by bacterial culture, Western blotting, immunohistochemistry, TUNEL assay, and flow cytometry.</p><p><strong>Results: </strong>OW significantly alleviated tail swelling and IVD structural damage. OW demonstrated potent antibacterial activity against <i>S. aureus</i>, disrupting bacterial membrane integrity. OW attenuated extracellular matrix degradation by upregulating collagen II and aggrecan while downregulating MMP3 and MMP9, and suppressed inflammatory responses (IL-1β, IL-6, TNF-α, Cox2) by inhibiting NF-κB p65 phosphorylation and nuclear translocation. OW also reduced NP cell apoptosis, evidenced by decreased TUNEL-positive rate, elevated Bcl-2/Bax ratio, and reduced Cleaved caspase-3.</p><p><strong>Conclusions: </strong>OW attenuates <i>S. aureus</i>-induced discitis through direct antibacterial action, suppression of NF-κB-mediated inflammation, protection against NP cell apoptosis, and preservation of extracellular matrix integrity, highlighting its promise as a novel lavage strategy for discitis management.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":" ","pages":"403-424"},"PeriodicalIF":1.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148263417","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":"Tissue zone dependence and asymmetric distribution of membrane ruffles of <i>in-situ</i> bovine chondrocytes.","authors":"Ali Ahmadi, Yazan Zeidat, Walter Herzog, Eng Kuan Moo","doi":"10.1080/03008207.2026.2695398","DOIUrl":"10.1080/03008207.2026.2695398","url":null,"abstract":"<p><strong>Purpose: </strong>The surface of chondrocytes is covered with membrane ruffles. Chondrocytes sense mechanical signals through cell membrane stretching and unfolding, a process mediated by the pericellular matrix (PCM). PCM is known to be thicker on the bone-facing (bf) inferior side than the surface-facing (sf) superior side, a feature thought to minimize membrane strain. Previously, we studied chondrocyte membrane morphology and noticed that membrane ruffles of some cells are concentrated at specific surface regions. We hypothesized that PCM asymmetry drives this non-uniform ruffle distribution.</p><p><strong>Methods: </strong>Fresh cartilage samples (<i>n</i> = 10) were harvested and histologically processed for electron microscopy. Cell membrane outline was tracked from micrographs. Cells were divided into bf inferior and sf superior halves and ruffle density was quantified as waviness and fractal dimension. The density and distribution of membrane ruffles were measured for chondrocytes in the superficial, middle, and deep zones of cartilage.</p><p><strong>Results: </strong>We found that membrane ruffles almost double the surface area of chondrocytes. Ruffle density is tissue zone-dependent; deep zone cells have ~20% less ruffles than superficial and middle zone cells. Asymmetric membrane ruffles were observed for cells in the top 100 µm of the tissue; the extent of asymmetry decreased with tissue depth.</p><p><strong>Conclusions: </strong>Chondrocyte membrane morphology is likely adapted to their mechanical and osmotic surroundings. Asymmetric membrane ruffles may be a multi-purpose strategy to increase membrane reservoir size and to deposit thick PCM layers for strain attenuation. This study highlights the importance of studying cells in their native environment to provide insights into <i>in-situ</i> cell mechanobiology.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":" ","pages":"457-465"},"PeriodicalIF":1.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148367208","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":"Autologous platelet-rich gel promotes diabetic foot ulcer wound healing by activating the Wnt/β-catenin signaling pathway.","authors":"Liangliang Du, Yuwei Dai, Jiayu Sui, Yuwen Liao, Yonghe Liu, Liusi Du, Douyun Zeng","doi":"10.1080/03008207.2026.2694527","DOIUrl":"10.1080/03008207.2026.2694527","url":null,"abstract":"<p><strong>Purpose: </strong>Diabetic foot ulcers (DFUs), a major cause of disability in diabetic patients, pose a significant clinical challenge. Autologous platelet-rich gel (APG), an advanced biotherapeutic approach, has demonstrated considerable potential in promoting DFU wound healing. This study aimed to investigate the therapeutic mechanisms of APG in DFU.</p><p><strong>Methods: </strong>A DFU model was established in streptozotocin-induced Sprague-Dawley rats. Wound closure rates were measured on days 7 and 14 post-injury. Histological evaluation was conducted using hematoxylin and eosin (H&E) staining. The expression of collagen I and III was assessed by immunohistochemistry (IHC). Activation of the Wnt/β-catenin pathway and related signaling molecules (NF-κB, STAT3) was determined by western blot analysis.</p><p><strong>Results: </strong>APG treatment significantly reduced wound area, enhanced granulation tissue formation and epithelial regeneration, and promoted the expression of collagen I and III. Mechanistically, APG specifically activated the Wnt/β-catenin pathway, as indicated by increased β-catenin protein levels. Importantly, the beneficial effects of APG on wound healing, tissue repair, and collagen deposition were effectively abolished by co-treatment with XAV-939.</p><p><strong>Conclusions: </strong>These findings reveal a novel mechanism underlying APG-mediated DFU healing and provide a theoretical foundation for the beneficial role of Wnt/β-catenin signaling in wound repair. This study offers new perspectives and directions for ulcer treatment strategies.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":" ","pages":"447-456"},"PeriodicalIF":1.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148403959","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":"Overexpression of NSUN3 suppresses ferroptosis in osteoarthritis chondrocytes by reducing m5C modification and expression of PCBP1 mRNA.","authors":"Wuluhan Mahan, Yelinaer Ayiheng, Zengru Xie","doi":"10.1080/03008207.2026.2668589","DOIUrl":"10.1080/03008207.2026.2668589","url":null,"abstract":"<p><strong>Purpose: </strong>Osteoarthritis (OA) is a degenerative joint disease, with chondrocyte ferroptosis a key pathogenic mechanism in its progression. The role of RNA 5-methylcytosine (m5C) modification in OA chondrocyte ferroptosis remains unclear. This study investigates the involvement and mechanisms of m5C-related regulatory factors in OA chondrocyte ferroptosis.</p><p><strong>Materials and methods: </strong>Differentially expressed genes (DEGs) between healthy and damaged knee cartilages were analyzed using GSE129147. Mouse chondrocytes were treated with Interleukin-1β (IL-1β) to induce in vitro OA model. Ferroptosis was evaluated by measuring malondialdehyde (MDA), Fe2+, glutathione peroxidase 4 (GPX4), superoxide dismutase (SOD), glutathione (GSH) levels, and ACSL4, SLC7A11, GPX4 protein levels. The mechanism was investigated via methylated RNA immunoprecipitation (MeRIP), RIP, and dual luciferase activity.</p><p><strong>Results: </strong>NSUN3 was downregulated in damaged human knee cartilage and IL-1β-induced mouse chondrocytes. IL-1β promoted chondrocyte death and ferroptosis, which was reversed by NSUN3 overexpression. NSUN3 expression positively correlated with PCBP1. NSUN3 increased PCBP1 expression and RNA stability via m5C modification. PCBP1 knockdown abolished the enhancing effects of NSUN3 on ferroptosis and cell death under IL-1β stimulation.</p><p><strong>Conclusions: </strong>NSUN3 overexpression inhibited ferroptosis in IL-1β-induced mouse chondrocytes by promoting PCBP1 expression via increased m5C modification on PCBP1. These in vitro findings offer preliminary insights into potential epigenetic regulatory mechanisms underlying chondrocyte ferroptosis in OA, although further in vivo validation is required.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":" ","pages":"365-376"},"PeriodicalIF":1.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834747","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":"Rotenone impairs osteoclastogenesis by inhibiting cell migration: insights from machine learning.","authors":"Chongjie Zhu, Chi Zhang, Mingjuan Li, Feng Li, Liu Liu, Chenxinzi Lin, Zubing Li, Zhi Li, Qilong Wan","doi":"10.1080/03008207.2026.2665186","DOIUrl":"10.1080/03008207.2026.2665186","url":null,"abstract":"<p><strong>Purpose: </strong>The migration and fusion of osteoclast precursors (OCPs) are critical steps in osteoclastogenesis and require substantial energy. Although oxidative phosphorylation (OXPHOS) is generally considered the major pathway supplying energy for these processes, it remains unclear how inhibiting OXPHOS affects the migration of OCPs.</p><p><strong>Materials and methods: </strong>To investigate the metabolic regulation of osteoclast migration, we used a recognized OXPHOS inhibitor rotenone to suppress the key energy-producing pathway in OCPs. We combined this intervention with bioinformatics approaches and machine learning algorithms to screen and identify genes associated with osteoclast dysfunction in patients with osteoporosis. The migratory capacity of OCPs was precisely quantified using optical tweezers.</p><p><strong>Results: </strong>We found that rotenone inhibited osteoclastogenesis and markedly impaired the migratory capacity of OCPs. Although the level of OXPHOS in OCPs decreased, intracellular ATP content paradoxically increased, suggesting that the impairment of migratory capacity is unlikely to be driven by an overall energy shortage. Through machine learning algorithms, we identified genes associated with abnormal osteoclast function in patients with osteoporosis and discovered their critical regulatory roles in processes such as cell migration, adhesion, and OXPHOS. Rotenone significantly suppressed the expression of these genes in OCPs, suggesting a direct mechanism for the impaired migration.</p><p><strong>Conclusions: </strong>In summary, our study reveals a novel mechanism for rotenone-induced inhibition of osteoclastogenesis, which is achieved by impairing the migration of OCPs in a manner uncoupled from overall energy status.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":" ","pages":"335-349"},"PeriodicalIF":1.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147764945","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}