Bone & Joint Research最新文献

{"title":"Oxygen tension alters cartilage redox balance in response to traumatic impact.","authors":"Jingyi Wang, Greta E Scheidt, Corinne R Henak","doi":"10.1302/2046-3758.156.BJR-2025-0436.R1","DOIUrl":"10.1302/2046-3758.156.BJR-2025-0436.R1","url":null,"abstract":"<p><strong>Aims: </strong>Redox balance plays a key role in cellular homeostasis. Disruption of redox balance contributes to initiation and progression of multiple diseases including osteoarthritis, a common joint disease that is characterized by progressive cartilage damage. Therefore, monitoring cartilage redox balance can be used to evaluate cartilage health and disease status. Previous studies have investigated the effect of oxygen tension and traumatic impact on cartilage redox balance separately, but their interplay is not well known. The aim of this study is to quantify time- and position-dependent peracute responses of cartilage redox balance to impact injury at controlled oxygen tension.</p><p><strong>Methods: </strong>Optical redox imaging (ORI) was used to evaluate redox balance in porcine cartilage explants. ORI measures the autofluorescence from cofactors in cellular redox reactions to provide a real-time evaluation of redox balance. Porcine cartilage explants underwent traumatic impact at normal (room) or low oxygen tension, with imaging before and after loading. Samples were snap frozen shortly after imaging for gene expression analysis. Achieved loading parameters were calculated based on high-speed camera images.</p><p><strong>Results: </strong>At normal oxygen tension, fluorescent intensity increased after impact loading in both channel 1 (corresponding to reduced nicotinamide adenine dinucleotide (NADH) and its phosphate (NADPH)) and channel 2 (corresponding to flavin adenine dinucleotide (FAD)), but this effect was not observed at low oxygen tension. In addition, a significant temporal effect was only observed for optical redox ratio (reflecting the relative accumulation of the cofactors), which was elevated after 28 minutes post-impact. Despite the measured changes in redox, gene expression did not change significantly.</p><p><strong>Conclusion: </strong>Low oxygen tension was protective against impact injury-induced autofluorescence changes. In addition, the response of cartilage redox balance to impact was progressive.</p>","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"15 6","pages":"601-609"},"PeriodicalIF":5.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13222727/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148136620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The design process for orthopaedic implants : an introduction.","authors":"Radovan Zdero, Pawel Brzozowski, Emil H Schemitsch, Irene Yang","doi":"10.1302/2046-3758.155.BJR-2025-0267.R3","DOIUrl":"10.1302/2046-3758.155.BJR-2025-0267.R3","url":null,"abstract":"<p><p>Orthopaedic implants consist of engineered devices for various surgical uses, such as plates or nails used to fix fractures; plates, rods, or cages used for spinal fusion, total hip or knee arthroplasties, and osteoconductive bone scaffolds. The implant design process typically involves the complicated interaction of interdisciplinary teams, client consultation, concept generation, concept ranking, prototype fabrication, engineering analysis, etc. However, the process can also be described as having four major aspects, each of which has a feedback loop if modifications are needed. The first is the design and fabrication, which can include factors such as geometry, surface finish, special features, material selection, and methods of fabrication. The second involves mechanical/engineering analysis, which could involve factors such as stress risers, stress shielding, elastic stiffness, failure strength, and fatigue life. The third is biological/clinical analysis, which may involve factors such as biocompatibility, bioresorbability, bone remodelling, surgical simplicity, and clinical outcomes. The fourth is marketplace evaluation, which might involve factors such as cost-effectiveness, patent acquisition, regulatory approval, demographic suitability, and ecological sustainability. These aspects, or the specific factors within each aspect, can occur sequentially step by step, simultaneously side by side, in different orders, or by some combination of all of these options. This article is a brief practical introduction to the design process for orthopaedic implants.</p>","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"15 5","pages":"577-582"},"PeriodicalIF":5.5,"publicationDate":"2026-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13213497/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148026919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum.","authors":"Xiao-Chen Fan, Jue Wang","doi":"10.1302/2046-3758.155.BJR-2026-00004","DOIUrl":"10.1302/2046-3758.155.BJR-2026-00004","url":null,"abstract":"","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"15 5","pages":"583"},"PeriodicalIF":5.1,"publicationDate":"2026-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13213495/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148026932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Does tibial sclerosis severity influence bone resorption risk following total knee arthroplasty? : finite element analysis considering implant design and surgical technique.","authors":"Jun Young Park, Kwan Kyu Park, Ji-Hoon Nam, Min-Cheol Hwang, Kyoung-Tak Kang, Byung Woo Cho","doi":"10.1302/2046-3758.155.BJR-2025-0473.R2","DOIUrl":"10.1302/2046-3758.155.BJR-2025-0473.R2","url":null,"abstract":"<p><strong>Aims: </strong>Stress shielding, particularly affecting the proximal medial tibial bone, is a significant concern following total knee arthroplasty (TKA). This study investigates how tibial sclerosis severity, implant configurations, and rotational alignment techniques influence bone resorption patterns in the medial proximal tibia.</p><p><strong>Methods: </strong>Finite element analysis (FEA) was performed using tibial models with four sclerosis levels (0 to 3) representing progressive sclerosis penetration. Four implant configurations combining baseplate shapes (symmetrical vs anatomical) and keel designs (longer (40 mm) vs shorter (30 mm)) were evaluated with two rotational alignment protocols, generating 32 models (4 × 4 × 2). Bone resorption rates in four medial cortical regions were quantified using strain energy density (SED) criteria.</p><p><strong>Results: </strong>A dose-dependent relationship was demonstrated between sclerosis severity and bone resorption rates. In the total medial cortical region, a substantial increase occurred at Level 3 over Level 0 (67.8% vs. 64.8%, respectively, p < 0.001). Keel design emerged as the dominant factor, with shorter keels demonstrating significantly lower absolute resorption rates than longer keels across all sclerosis levels (59.9% to 64.0% vs. 69.8% to 71.7%, p = 0.029). However, when changes were analyzed relative to baseline sclerosis severity, shorter keels exhibited significantly greater increases in bone resorption rates than longer keels (4.1% vs 1.9% at Level 3, p = 0.029), indicating greater sensitivity to sclerosis progression. Contrary to implant configurations, no significant differences were observed between the maximum-coverage method and Insall's method across all sclerosis severity levels (p = 0.486).</p><p><strong>Conclusion: </strong>Proximal medial tibial sclerosis severity demonstrates a clear dose-dependent relationship with bone resorption risk following TKA. Although shorter keel configurations provide lower absolute bone resorption rates, they exhibit greater sensitivity to sclerosis progression than longer keels. Rotational alignment techniques showed no significant effects on bone resorption patterns in sclerotic bone conditions. These findings support preoperative sclerosis assessment for surgical planning and highlight the complex interaction between implant design and bone quality.</p>","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"15 5","pages":"566-576"},"PeriodicalIF":5.5,"publicationDate":"2026-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13202488/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148026973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Naringin targets TGF-β1-mediated angiogenesis to enhance the osteogenic effect of induced membrane.","authors":"Shuyuan Li, Qunbin Cai, Songyang Wang, Zhanpeng Zeng, Dawen Yang, Qishi Zhou","doi":"10.1302/2046-3758.155.BJR-2025-0412.R1","DOIUrl":"10.1302/2046-3758.155.BJR-2025-0412.R1","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Aims: &lt;/strong&gt;Induced membrane technique (IMT) is a novel two-stage reconstruction technology for large bone defects. As is widely known, promoting the vascularization of induced membrane tissue is of great importance in accelerating the mineralization process of bone graft. Naringin is a flavonoid compound with anti-inflammatory, anti-osteoporotic, and potential pro-angiogenic effects. The aim of this study is to explore the effect and mechanism of naringin on angiogenesis of induced membrane.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A total of 48 SD rats were randomly divided into a control group, low-dose group (L-Naringin), medium-dose group (M-Naringin), and high-dose group (H-Naringin). All rats underwent the establishment of an IMT model in the right femur. Four weeks after the first-stage surgery, which coincided with the completion of four weeks of treatment with different doses of naringin, the results of angiogenesis and cell proliferation within the induced membrane were evaluated. Eight weeks after the second-stage surgery, imaging and histological methods were employed to assess the healing of femoral bone defects and analyze the impact of induced membranes with varying vascular densities on the mineralization of bone grafts. The naringin-containing serum was collected from rats to cultivate endothelial progenitor cells (EPCs) derived from rat bone marrow in vitro. The effects of naringin on the proliferation, migration, angiogenesis, and transforming growth factor β (TGF-β)/SMAD signalling pathway of EPCs were assessed at corresponding stages. Meanwhile, the conditioned medium (CM) from EPCs was collected to treat osteoblasts, analyzing the effect of EPCs-derived angiogenic-osteogenic factors on osteoblast mineralization. Finally, naringin binding to TGF-β1 protein was studied by molecular docking, molecular dynamics simulation (MDS), and cellular thermal shift assay (CETSA).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Compared with control and L-Naringin groups, the vascular number, cell proliferation rate, and TGF-β/SMAD pathway-related factors (TGF-β1, phosphorylated-SMAD (p-SMAD)2, and p-SMAD3) of the induced membrane were higher in the M-Naringin and H-Naringin groups. Meanwhile, the richer the blood vessels within the induced membrane, the stronger the mineralization capacity of the bone graft, and the faster the healing rate of the bone defect. In vitro, naringin-containing serum intervention notably increased cell viability, migration, tubular formation, secretion of angiogenic-osteogenic factors, and phosphorylation level of TGF-β/SMAD signalling pathway-related proteins in EPCs (p &lt; 0.05 in the naringin group, vs the control group). Meanwhile, naringin-containing serum reversed the inhibitory effect of small interfering-TGF-β1 (si-TGF-β1) on the function of EPCs (p &lt; 0.05 in the si-TGF-β1+ naringin group, vs the si-TGF-β1 group). The CM experiment demonstrated that angiogenic-osteogenic factors derived from EPCs could promote the ","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"15 5","pages":"549-565"},"PeriodicalIF":5.5,"publicationDate":"2026-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13196827/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147986554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ultrasound-triggered microbubble delivery of voriconazole for enhanced reduction of Candida albicans biofilms in vitro.","authors":"Rui Liu, Liqin Yao, Qiangde Hu, Chen Zou, Boyong Xu, Li Cao, Wenbo Mu","doi":"10.1302/2046-3758.155.BJR-2025-0459.R2","DOIUrl":"10.1302/2046-3758.155.BJR-2025-0459.R2","url":null,"abstract":"<p><strong>Aims: </strong>This study aimed to develop voriconazole-loaded microbubbles (MBs@VRC) combined with ultrasound-targeted microbubble destruction (UTMD) as a novel strategy to disrupt <i>Candida albicans</i> biofilms and enhance antifungal efficacy, addressing the critical challenge of biofilm-associated resistance in fungal periprosthetic joint infections (PJIs).</p><p><strong>Methods: </strong>MBs@VRC were produced using a thin-film hydration method, and their physicochemical properties were evaluated, including size, zeta potential, and drug loading efficiency. The penetration of DiI-labelled MBs@VRC into <i>C. albicans</i> biofilms was visualized via confocal laser scanning microscopy (CLSM). The antibiofilm activity of the UTMD + MBs@VRC treatment was comprehensively assessed on polystyrene, glass, and titanium surfaces using crystal violet staining (biomass quantification), live/dead staining (viability and thickness analysis), scanning electron microscopy (SEM, morphological evaluation), and colony-forming unit (CFU) counting. Furthermore, the cytocompatibility of MBs@VRC was evaluated in RAW 264.7 macrophages.</p><p><strong>Results: </strong>The synthesized MBs@VRC exhibited a uniform spherical morphology with a mean diameter of 500.87 nm (SD 6.94) and an encapsulation efficiency of 35.33% (SD 2.52%). While <i>C. albicans</i> biofilms showed a notable increase in tolerance, with a minimum biofilm eradication concentration (MBEC₅₀) (1,966.08 μg/ml) approximately 66,000-fold higher than the planktonic minimum inhibitory concentration (MIC) (0.03 μg/ml), MBs@VRC successfully penetrated deep into the 3D biofilm architecture. Compared to monotherapies, the UTMD + MBs@VRC markedly reduced biofilm biomass (by approximately 63% on glass and 73% on titanium), reduced biofilm thickness (as quantified on glass, by approximately 68%), and reduced the viability of <i>C. albicans</i> (by approximately 66% on glass; by approximately 84% on titanium). SEM imaging confirmed extensive hyphal rupture and structural collapse in the combination group. No significant cytotoxicity was observed, with cell viability remaining above 90%.</p><p><strong>Conclusion: </strong>MBs@VRC combined with UTMD effectively disrupts <i>C. albicans</i> biofilms, enhances targeted drug delivery and release, and significantly improves antifungal activity without detectable cytotoxicity. This approach represents a promising adjunctive therapy for combating recalcitrant fungal biofilm infections.</p>","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"15 5","pages":"537-548"},"PeriodicalIF":5.5,"publicationDate":"2026-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13187755/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147970098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MRI-based radiomics explainable model for predicting recurrence of limb chronic osteomyelitis in limb bones treated by Masquelet technique.","authors":"Yi Cao, Xuesen Zhao, Ruofei Wang, Fu Hao, Zekun Zhang, Tao Zhang, Liqiang Li, Dong Ma","doi":"10.1302/2046-3758.155.BJR-2025-0385.R1","DOIUrl":"10.1302/2046-3758.155.BJR-2025-0385.R1","url":null,"abstract":"<p><strong>Aims: </strong>This study aimed to develop a machine learning model for predicting chronic osteomyelitis recurrence (COR) following the Masquelet technique (MT). The model integrated MRI-based radiomics with clinical characteristics to guide the definitive treatment of bone defects in limb chronic osteomyelitis (LCO).</p><p><strong>Methods: </strong>We retrospectively analyzed data from patients with chronic osteomyelitis who underwent debridement and the Masquelet technique (MT) as definitive treatment at two medical centres between 2015 and 2023. The dataset included demographics, MRI scans, clinical characteristics, and infection recurrence, with a two-year follow-up period. Radiomics features were extracted from MRI-images using PyRadiomics. Clinical features were identified by logistic regression analyses. A COR predictive model was developed using machine learning algorithms and SHapley Additive exPlanations (SHAP). Additionally, a web-based application was also constructed to support the model.</p><p><strong>Results: </strong>Among 279 patients (mean age, 43.19 years (SD 11.87); 195 men and 84 women), 59 (21.15%) patients had COR, involving the hip, lower limb, foot, and upper limb. The radiomic feature \"Radscore\" was constructed by eight image features. Four significant clinical features (age, surgery times, duration of infection, ESR) were selected, and combined with radiomics feature to construct a predictive model using machine learning algorithms. This integrated model exhibited a superior performance (area under the curve (AUC) = 0.901, 0.952, and 0.910 in training, validation, and external validation cohort, respectively) than only clinical (AUC = 0.862) or radiomics (AUC = 0.684) model. Lastly, a web-based application was developed and validated to predict COR risk in patients with MT treatment.</p><p><strong>Conclusion: </strong>A web-based application integrating radiomics and clinical factors was developed to predict risk of COR in patients after MT treatment, allowing for the implementation of preventive interventions and targeted management.</p>","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"15 5","pages":"508-518"},"PeriodicalIF":5.5,"publicationDate":"2026-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13169451/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147926268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex-specific hormonal rescue of bone growth in PAPPA2-deficient mice : a role for cannabinoid receptors and STAT3.","authors":"María Del Mar Fernández-Arjona, Antonio J López-Gambero, Leticia Rubio, Miguel Rodríguez-Pozo, Patricia Rivera, Marialuisa de Ceglia, Antonio Vargas, Fernando Rodríguez de Fonseca, Julie A Chowen, Jesús Argente, Juan Suárez","doi":"10.1302/2046-3758.155.BJR-2025-0563.R1","DOIUrl":"10.1302/2046-3758.155.BJR-2025-0563.R1","url":null,"abstract":"<p><strong>Aims: </strong>Recombinant human (rh) insulin-like growth factor-1 (IGF1) treatment has been shown to restore growth velocity and height in children harbouring pregnancy-associated plasma protein-A2 (<i>PAPP-A2</i>) mutations. The present study aimed to evaluate whether pharmacological modulation of the growth hormone (GH)/IGF1 system elicits sex-specific improvements in bone growth in a <i>pappalysin 2 (Pappa2)-</i>deficient mouse model of growth impairment, and to identify the associated signalling pathways.</p><p><strong>Methods: </strong><i>Pappa2</i> knockout (<i>Pappa2^ko/ko</i>) mice of both sexes received daily treatment with rhGH, rhIGF1, or rhPAPP-A2 from postnatal day (PND) 5 to PND 35. The IGF1 system, bone remodelling factors, cannabinoid receptors, and intracellular signalling were analyzed in bone.</p><p><strong>Results: </strong>At the onset of puberty, hormone-treated knockout <i>Pappa2</i> (<i>Pappa2^ko/ko</i>) mice exhibited increased body length and weight, along with a higher femur weight-to-length ratio following rhGH or rhPAPP-A2 administration. In <i>Pappa2^ko/ko</i> females, hormone treatments reduced the bone resorption marker osteopontin, particularly following rhPAPP-A2, which also led to decreased expression of cannabinoid receptors (<i>CNR1</i>, <i>CNR2</i>, and <i>GPR55</i>). Compared to rhGH, both rhPAPP-A2 and rhIGF1 specifically decreased the IGF binding protein <i>Igfbp5</i> and increased expression of the bone formation markers osteocalcin and collagen I in females. These effects were accompanied by elevated levels of phosphorylated signal transducer and activator of transcription 3 (STAT3). <i>Pappa2</i> deficiency and hormone therapy were associated with numerous sex-specific differences in bone IGF1 binding, bone remodelling, cannabinoid receptors, and signal transducer and activator of transcription 3 (STAT3) signalling.</p><p><strong>Conclusion: </strong>These findings support rhPAPP-A2 as a promising therapeutic candidate for mitigating postnatal bone growth retardation by increasing bone formation and reducing resorption through cannabinoid receptor modulation in a female-specific manner.</p>","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"15 5","pages":"519-536"},"PeriodicalIF":5.5,"publicationDate":"2026-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13169458/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147926262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune profiling in orthopaedic diseases using mass cytometry : a narrative review of applications and future directions.","authors":"Yosuke Susuki, Monica Thukkaram, Issei Shinohara, Masatoshi Murayama, Mayu Morita, Takahiro Igei, Chao Ma, Alexa K Pius, Qi Gao, Simon Kwoon-Ho Chow, Stuart B Goodman","doi":"10.1302/2046-3758.155.BJR-2025-0548.R1","DOIUrl":"10.1302/2046-3758.155.BJR-2025-0548.R1","url":null,"abstract":"<p><strong>Aims: </strong>Musculoskeletal (MSK) diseases involve complex immune mechanisms. Conventional flow cytometry is restricted by spectral overlap, limiting multidimensional immune characterization. Mass cytometry by time-of-flight (CyTOF) can measure over 40 proteins per cell using metal-tagged antibodies and time-of-flight detection, providing deep immune phenotyping. The aim of this narrative review was to summarize the applications of CyTOF in the study of human orthopaedic and rheumatic diseases, highlight key immune findings including shared markers, and identify gaps to guide future research and panel standardization.</p><p><strong>Methods: </strong>A literature search of peer-reviewed studies published from 1 January 2014 to 31 December 2024 was conducted using PubMed, Scopus, and Web of Science. Search terms included \"CyTOF\" and \"mass cytometry\". Studies were included if CyTOF was applied to human MSK disorders with immune or inflammatory components and if the full text was available in English. Data extracted included disease type, sample source, computational pipeline, immune cell types analyzed, and main findings.</p><p><strong>Results: </strong>A total of 22 studies were included. Since some studies reported results for more than one disease, the total number of disease-specific entries was 26: rheumatoid arthritis (n = 13), osteoarthritis (n = 4), psoriatic arthritis (n = 3), juvenile idiopathic arthritis (n = 2), ankylosing spondylitis (n = 1), idiopathic inflammatory myopathies (n = 1), and post-surgical immune monitoring (n = 2). Human models were represented. CyTOF identified disease-specific immune cell subsets, cytokine profiles, and treatment-response signatures. No eligible studies addressed osteoporosis or osteonecrosis likely reflecting that these conditions would yield low immune-cell density and/or technical challenges in acquiring bone tissue. Eight recurrent markers emerged across diseases: program cell death protein 1 (PD-1), inducible T-cell costimulator (ICOS), CXC motif chemokine receptor (CXCR)5, CXCR4, phosphorylated signal transducer and activator of transcription 4 protein (pSTAT3), tumour necrosis factor receptor II (TNFRII), p16 inhibitor of cyclin-dependent kinase 4a (p16INK4a), and cluster of differentiation (CD)180, which reflect shared pathways of inflammation, senescence, and tissue damage.</p><p><strong>Conclusion: </strong>CyTOF enables high-dimensional immune profiling in MSK diseases, offering insights into pathogenesis, treatment response, and patient stratification. Broader application of this technology to underexplored conditions is warranted. A minimal eight-marker backbone may enhance panel harmonization and support future multicentre translational studies in orthopaedic immunology.</p>","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"15 5","pages":"497-507"},"PeriodicalIF":5.5,"publicationDate":"2026-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13169456/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147926254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Kaempferol suppresses fibroblast-like synoviocyte proliferation in rheumatoid arthritis by targeting glutamate-cysteine ligase modifier subunit to inhibit ferroptosis resistance.","authors":"Yi Ling, Zehong Luo, Nina Ren, Xuemei Yuan, Feng Luo, Hui Xu, Changming Chen, Daomin Lu, Qiuyi Wang, Xueming Yao, Wukai Ma","doi":"10.1302/2046-3758.155.BJR-2025-0419.R2","DOIUrl":"10.1302/2046-3758.155.BJR-2025-0419.R2","url":null,"abstract":"<p><strong>Aims: </strong>Kaempferol has demonstrated promising therapeutic potential in the treatment of rheumatoid arthritis (RA), yet its underlying mechanisms remain to be fully elucidated. This study aimed to investigate the role of kaempferol in modulating ferroptosis resistance in tumour necrosis factor-alpha (TNF-α)-induced fibroblast-like synoviocytes (RA-FLS), and to explore its molecular targets and signalling pathways involved in RA progression.</p><p><strong>Methods: </strong>Proteomic and transcriptomic analyses were employed to identify the key pathways regulated by kaempferol in TNF-α-induced RA-FLS. The effects of kaempferol on oxidative stress, ferroptosis, and cellular proliferation in RA-FLS were evaluated using flow cytometry, measurements of malondialdehyde (MDA) and superoxide dismutase (SOD) activity, FerroOrange staining, transmission electron microscopy (TEM), cell counting kit (CCK-8) assay, and 5-ethynyl-2-deoxyuridine (EdU) assay. Protein and messenger RNA (mRNA) expression levels were validated using Western blotting and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Additionally, a TNF-α-induced collagen-induced arthritis (CIA) rat model was established to examine the anti-inflammatory and antiproliferative effects of kaempferol in vivo. The functional role of the glutamate-cysteine ligase modifier (GCLM) subunit was further investigated using GCLM-overexpressing RA-FLS models.</p><p><strong>Results: </strong>Kaempferol significantly modulated oxidative phosphorylation and glutathione metabolism pathways, reducing reactive oxygen species (ROS) and lipid peroxidation levels in RA-FLS. It suppressed TNF-α-induced RA-FLS proliferation by promoting ROS accumulation and inducing ferroptosis. In the CIA model, kaempferol effectively alleviated joint swelling and reduced inflammatory cytokine levels. Mechanistically, kaempferol downregulated GCLM expression in RA-FLS, resulting in decreased p65 nuclear translocation and inhibition of nuclear factor kappa B (NF-κB) activation. This regulatory effect restored intracellular ROS, thereby overcoming ferroptosis resistance and inhibiting synoviocyte hyperproliferation.</p><p><strong>Conclusion: </strong>Kaempferol exerts anti-inflammatory and antiproliferative effects in RA by targeting the GCLM/NF-κB signalling axis. By restoring ROS and iron homeostasis and overcoming ferroptosis resistance, kaempferol inhibits RA-FLS proliferation and mitigates synovial inflammation, suggesting its potential as a novel therapeutic agent for RA treatment.</p>","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"15 5","pages":"482-496"},"PeriodicalIF":5.5,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13152675/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}