Bone最新文献

{"title":"Bone metabolism in heterotopic ossification is primarily influenced by the time after trauma or surgery, independent of anatomic location","authors":"Simon von Kroge ,&nbsp;Gesine Eis-Janzyk ,&nbsp;Anke Baranowsky ,&nbsp;Assil-Ramin Alimy ,&nbsp;Mustafa Citak ,&nbsp;Frank Timo Beil ,&nbsp;Karl-Heinz Frosch ,&nbsp;Konrad Mader ,&nbsp;Johannes Keller ,&nbsp;Tim Rolvien","doi":"10.1016/j.bone.2025.117604","DOIUrl":"10.1016/j.bone.2025.117604","url":null,"abstract":"<div><div>Although several risk factors and prophylactic measures for heterotopic ossification (HO) have been identified in the past, knowledge about its growth and metabolic activity over time remains limited. This study aimed to identify specific characteristics of HO metabolism and time-dependent activity shared at two of the most prevalent sites of HO, namely HO after elbow trauma and total hip arthroplasty. Thirty-six HO specimens (elbow/hip: 11/25) were analyzed using histological analysis of central and peripheral regions, and quantitative backscattered electron imaging. All data were compared with iliac crest samples of healthy donors (<em>n</em> = 11) and analyzed based on the time after initial trauma or surgery. Both elbow and hip HO were characterized by signs of endochondral ossification and exhibited high proportions of woven bone and low matrix mineralization. Ongoing ossification was observed frequently along the HO rim, and high bone remodeling was evident, particularly in elbow HO. While elbow HO specimens were obtained at earlier stages, most characteristics were comparable to hip HO when matching for the time after trauma or surgery. Ongoing ossification did not change significantly with time after trauma, but the woven bone proportion and osteocyte density decreased, particularly in the first three years, while the calcium content increased inversely. Taken together, both elbow and hip HO are characterized by immature, woven bone that is metabolically highly active, especially within the first three years after trauma. Reduced metabolic activity and signs of bone maturation suggest that the risk of recurrence may be reduced if resection is performed at a later time point after trauma or surgery.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"200 ","pages":"Article 117604"},"PeriodicalIF":3.6,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144748656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"How vascularization is reciprocally coupled to chondrogenesis and osteogenesis in bone healing: lessons from the growth plate","authors":"Julia Mehl ,&nbsp;Katharina Schmidt-Bleek ,&nbsp;Agnes Ellinghaus ,&nbsp;Stefan Mundlos ,&nbsp;Holger Gerhardt ,&nbsp;Georg N. Duda ,&nbsp;Viola Vogel","doi":"10.1016/j.bone.2025.117595","DOIUrl":"10.1016/j.bone.2025.117595","url":null,"abstract":"<div><div>Despite considerable progress, the underlying mechanisms that enable scar-free regeneration in bone after injury are still not well understood. Here, we compared the spatiotemporal distribution of SOX9-positive chondrocytes, SPARC-positive hypertrophic chondrocytes and osteoblasts, versus Osterix-positive osteoblasts, i.e. key cell types in cartilage and bone formation, in the fracture gap of a mouse osteotomy model with the orderly sequence of events observed in the growth plate. We show that external mechanical stability determines the spatial distribution of osteoblastic and chondrogenic cell populations at day 7, thus defining the site of chondrogenesis initiation. At day 14, only rigid, but not semi-rigid fixation promoted the formation of avascular regions within previously vascularized areas. We thus propose a model how mechanical stabilization promotes bone healing: Blood vessel growth into the hematoma is followed by localized vascular degradation as chondrogenesis progresses, ultimately leading to vascular regrowth via endochondral ossification initiated at the tips of the distal bones. Deepening our understanding of these processes and how they ultimately relate to scar-free bone regeneration is of significant medical relevance as they can provide instructions how to promote fracture healing.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"200 ","pages":"Article 117595"},"PeriodicalIF":3.6,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144762675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treating osteoporosis with denosumab or bisphosphonates in the long term: facts, uncertainties and assumptions. A narrative review by the clinical action group of the European Calcified Tissue Society (ECTS)","authors":"Anda Mihaela Naciu ,&nbsp;Gaia Tabacco ,&nbsp;Andrea Palermo ,&nbsp;Maria P. Yavropoulou ,&nbsp;Tim Rolvien ,&nbsp;Stella D'Oronzo ,&nbsp;John J. Carey ,&nbsp;Julien Paccou ,&nbsp;Willem Lems ,&nbsp;Athanasios D. Anastasilakis","doi":"10.1016/j.bone.2025.117600","DOIUrl":"10.1016/j.bone.2025.117600","url":null,"abstract":"<div><div>Osteoporosis is a chronic disease that requires long-term management, particularly in high-risk patients who have a substantial increase in fracture risk. Antiresorptive medications remain the most widely used treatment for osteoporosis. This review aims to evaluate the available evidence on the long-term effects of bisphosphonates and denosumab, in order to help physicians determine the most suitable long-term management regimen for their patients, while balancing efficacy, safety, and fracture risk. Both bisphosphonates and denosumab have demonstrated efficacy in reducing fracture risk and increasing bone mineral density for up to 10 years. However, evidence to support their safety and efficacy beyond this period remains scarce. Given the increasing number of patients being treated with bisphosphonates or denosumab in the long term, we strongly advocate conducting observational follow-up studies in these patients. Currently, treatment decisions are based on personal experience and expert opinions, as well as discussions with the patient within a shared decision-making framework. We hope that this manuscript will give important background information for these discussions and facilitate final decisions.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"200 ","pages":"Article 117600"},"PeriodicalIF":3.5,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144713971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “The high-bone-mass phenotype of novel transgenic mice with LRP5 A241T mutation” [Bone 187 (2024) 117172]","authors":"Xueting Wang ,&nbsp;Hui Zhang ,&nbsp;Ling Hu ,&nbsp;Jin He ,&nbsp;Qifeng Jiang ,&nbsp;Lingfei Ren ,&nbsp;Ke Yu ,&nbsp;Mengdie Fu ,&nbsp;Zhikun Li ,&nbsp;Zhixu He ,&nbsp;Junhao Zhu ,&nbsp;Ying Wang ,&nbsp;Zhiwei Jiang ,&nbsp;Guoli Yang","doi":"10.1016/j.bone.2025.117596","DOIUrl":"10.1016/j.bone.2025.117596","url":null,"abstract":"","PeriodicalId":9301,"journal":{"name":"Bone","volume":"200 ","pages":"Article 117596"},"PeriodicalIF":3.6,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144710285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating the usage of human placental tissue-derived xenograft in a surgically induced murine fracture model","authors":"Upasana Ganguly ,&nbsp;Tyler J. Margetts ,&nbsp;Will Varner Anou ,&nbsp;Murad K. Nazzal ,&nbsp;Reginald S. Parker ,&nbsp;Hanyu Xia ,&nbsp;Ashlyn J. Morris ,&nbsp;Abdullahi Warsame ,&nbsp;Sarah L. Mostardo ,&nbsp;Kuldeep Yadav ,&nbsp;Rachel J. Blosser ,&nbsp;Istvan Gergely ,&nbsp;Aamir Tucker ,&nbsp;Sonali J. Karnik ,&nbsp;Jiliang Li ,&nbsp;David L. Waning ,&nbsp;Amy Creecy ,&nbsp;Jill C. Fehrenbacher ,&nbsp;Melissa A. Kacena","doi":"10.1016/j.bone.2025.117599","DOIUrl":"10.1016/j.bone.2025.117599","url":null,"abstract":"<div><div>Impaired bone fracture healing can lead to chronic pain, loss of function, or life-long complications which can lead to limb-amputation. This study evaluated the effectiveness of human placental tissue-derived xenograft preparations (Connective Tissue Matrix, [CTM Biomedical®]) in promoting bone healing and reducing post-fracture pain behaviors using a preclinical, surgically induced, murine fracture model. CTM is thought to contain structural proteins and growth factors important for fracture healing. An intramedullary nail was used to stabilize the femur, and a mid-shaft femoral fracture was induced in 12-week-old male C57BL/6 J mice. Mice were divided into four groups (Saline Control, CTM Membrane, CTM Paste, and CTM Membrane + Paste). Complete blood count (CBC) and pain behavioral assessments were performed weekly. Modified radiographic union for tibial fracture (mRUST) scoring was used to assess healing from bi-weekly X-rays. Mice were euthanized 23 days post-fracture (dpf), and femurs were collected for μCT analysis and biomechanical or histomorphometric analyses. No significant changes in CBC were observed in any group. Compared to Saline Control, CTM Membrane (<em>p</em> = 0.002) and CTM Membrane + Paste (<em>p</em> = 0.04) treated groups exhibited a reduced pain score 4 dpf (grimace scores). μCT and histomorphometry showed that CTM Membrane + Paste group had significantly higher callus area (<em>p</em> = 0.01) and % bone (<em>p</em> = 0.001) compared to Saline Controls. mRUST scores, endomucin staining, and biomechanical outcomes between groups were not different. Preclinical findings suggest that CTM Membrane + Paste exhibits potential in enhancing bone healing. CTM products also do not increase pain behaviors in the surgical fracture model.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"200 ","pages":"Article 117599"},"PeriodicalIF":3.6,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144719259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exposure to maternal smoking during pregnancy and lifelong smoking: Association with vertebral dimensions in middle age","authors":"Milla Suominen ,&nbsp;Petteri Oura ,&nbsp;Jaakko Niinimäki ,&nbsp;Jaro Karppinen ,&nbsp;Eveliina Heikkala","doi":"10.1016/j.bone.2025.117597","DOIUrl":"10.1016/j.bone.2025.117597","url":null,"abstract":"<div><div>Exposure to maternal smoking during pregnancy is negatively associated with bone development, however, some studies have reported null findings. Offsprings' smoking behavior may also relate to bone structure. However, it is unclear whether smoking relates to vertebral size. We investigated whether maternal smoking during pregnancy or offsprings' lifelong smoking from ages five years to 46 years is associated with vertebral dimensions in middle age.</div><div>A total of 566 offspring from the Northern Finland Birth Cohort 1966 underwent lumbar magnetic resonance imaging at age 46 years. Complete data were available. We utilized previously identified maternal smoking trajectories and offsprings' lifelong smoking trajectories as exposures, used cross-sectional area (CSA) and volume of the fourth lumbar vertebra as study outcomes, and considered sex, parental socioeconomic status, lifelong body mass index, lifelong physical activity, and education as potential confounders in general linear models.</div><div>The “late adult quitters” were associated with larger CSA (Beta [B] coefficient 0.9, 95 % confidence interval 0.4–1.5) and volume (2.2, 0.4–4.0) than the “non-smokers.” After adjustments, the B coefficient of CSA attenuated but remained statistically significant (0.5, 0.1–0.9), while the B coefficient of the volume attenuated to non-significant (0.7, −0.6 to 2.0). Other lifelong smoking trajectories or maternal smoking trajectories during pregnancy were unrelated to the study's outcomes. There was no negative association between vertebral size and lifelong smoking or maternal smoking during pregnancy. However, more research with larger samples and objective exposure data is warranted to confirm these findings.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"200 ","pages":"Article 117597"},"PeriodicalIF":3.5,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144683813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Growth failure in aggrecan deficiency is due to decreased extracellular matrix and impaired growth plate chondrocyte hypertrophy","authors":"Ameya Bendre ,&nbsp;Lars Ottosson ,&nbsp;Marta Baroncelli ,&nbsp;Zelong Dou ,&nbsp;Ola Nilsson","doi":"10.1016/j.bone.2025.117594","DOIUrl":"10.1016/j.bone.2025.117594","url":null,"abstract":"<div><div>Heterozygous loss-of-function mutations in the aggrecan (<em>ACAN</em>) gene cause autosomal dominant short stature often associated with advanced bone age, early-onset osteoarthritis and intervertebral disc disease (SSOAOD). These mutations are relatively common in patients with idiopathic short stature. However, the pathogenic mechanism of growth failure in this condition is not fully understood. Here, we studied the heterozygous cartilage matrix deficiency mouse (<em>Acan</em>^{<em>+/−</em>}), which harbors a 7 bp microdeletion in aggrecan and develops postnatal growth cessation despite being born of normal size. Using detailed histomorphometric analysis, we found that the growth failure was primarily due to decreased extracellular matrix and impaired chondrocyte hypertrophy, whereas proliferation was largely unaffected. Furthermore, single-cell transcriptomic profiling revealed decreased total <em>Acan</em> mRNA expression in the <em>Acan</em>^{<em>+/−</em>} chondrocytes. Notably, Akt signalling, which is important for hypertrophic differentiation was suppressed in <em>Acan</em>^{<em>+/−</em>} pre-hypertrophic and hypertrophic chondrocytes. The decreased Akt signalling was associated with increased expression of calcium-calmodulin dependent protein kinase 1D (<em>Camk1D</em>), which negatively regulates Akt signalling, thereby providing a potential mechanism for the impaired hypertrophic differentiation. These findings reveal key cellular and molecular causes of growth failure in aggrecan deficiency and suggest that boosting proteoglycan expression and Akt signalling may help restore growth.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"200 ","pages":"Article 117594"},"PeriodicalIF":3.5,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144676844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Machine learning-driven clinical decision support for low bone mineral density: A web-based prediction model with explainable AI integration","authors":"Xing Yang ,&nbsp;Jianyuan Liu ,&nbsp;Xiaozhi Huang ,&nbsp;Hao Liang ,&nbsp;Ping Cui ,&nbsp;Shiran He ,&nbsp;Heng Zhang ,&nbsp;Wenping Liao ,&nbsp;Guangkun Zhang ,&nbsp;Qianqian Huang ,&nbsp;Huan Ning ,&nbsp;Tingyan Luo ,&nbsp;Yinghua Luo ,&nbsp;Wei Li ,&nbsp;Jiegang Huang","doi":"10.1016/j.bone.2025.117592","DOIUrl":"10.1016/j.bone.2025.117592","url":null,"abstract":"<div><h3>Background</h3><div>Low bone mineral density (LBMD), which includes osteopenia and osteoporosis, is associated with substantial health care costs. However, current diagnostic methods for LBMD are limited in terms of accuracy and accessibility. This study aims to develop an interpretable machine learning model for LBMD risk assessment and implement it as a web-based clinical decision support tool.</div></div><div><h3>Methods</h3><div>Data from subjects who underwent dual-energy X-ray absorptiometry (DXA) at the People's Hospital of Guangxi Zhuang Autonomous Region were collected and randomly divided into a training set (70 %) and an internal validation set (30 %). An external validation set was sourced from the National Health and Nutrition Examination Survey (NHANES) database. Least absolute shrinkage and selection operator (LASSO) regression and multiple logistic regression were used for feature selection. Ten common machine learning models were conducted based on the selected features. Model performance was assessed using the area under the receiver operating characteristic curve (AUC), Matthews correlation coefficient (MCC), Brier score, and decision curve analysis (DCA). The decision mechanisms of the best-performing model were explained using SHapley Additive exPlanations (SHAP) and Local Interpretable Model-agnostic Explanations (LIME). The optimal model was deployed as a web application using Streamlit.</div></div><div><h3>Results</h3><div>A total of 16,274 participants were included in this study. Age, body mass index (BMI), alkaline phosphatase, and total cholesterol were identified as key predictors of LBMD. The logistic regression (LR) model demonstrated superior prediction performance (internal validation set [AUC = 0.902, MCC = 0.684, Brier score = 0.123], external validation set [0.812, 0.358, 0.265]). DCA confirmed its clinical utility. Both SHAP and LIME showed consistent results in identifying predictive factors. The LR model was deployed as a web application to predict LBMD.</div></div><div><h3>Conclusion</h3><div>Our interpretable machine learning model and web-based implementation provide a free and reliable tool for predicting LBMD, which represents a significant advancement in making LBMD screening more accessible and cost-effective.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"200 ","pages":"Article 117592"},"PeriodicalIF":3.5,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144651513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrin-linked kinase-mediated promotion of osteogenic differentiation in bone marrow mesenchymal stem cells: A driver of heterotopic ossification in ankylosing spondylitis","authors":"Zhixiang Huang ,&nbsp;Yinyu Li ,&nbsp;Guozhen Hu ,&nbsp;Jiali Ding ,&nbsp;Meng Liu ,&nbsp;Yukai Huang ,&nbsp;Xuechan Huang ,&nbsp;Tianwang Li","doi":"10.1016/j.bone.2025.117591","DOIUrl":"10.1016/j.bone.2025.117591","url":null,"abstract":"<div><div>Excessive osteogenesis in bone marrow mesenchymal stem cells (BMSCs) contributes to the ectopic ossification associated with ankylosing spondylitis (AS), yet the underlying mechanisms are not fully understood. Integrin-linked kinase (ILK) plays an important role in the inflammatory process of AS, but its expression and effects on osteophytogenesis require further evaluation. Hence, we aimed to explore the role and mechanisms of ILK in the syndesmophyte formation of AS. After establishing the BMSC lines, the mineralization potential of BMSCs from AS patients (AS-BMSCs) was found to be greater than BMSCs of healthy volunteers (HV-BMSCs). The expression of ILK was consistent with the osteogenic hyperactivity of AS-BMSCs. Additionally, knockdown of ILK using small interfering ribonucleic acid suppressed osteogenic differentiation in BMSCs. Conversely, ILK upregulation via lentiviral transfection promoted their osteogenesis. The activity of protein kinase B (Akt)/ glycogen synthase kinase-3β (GSK-3β)/ β-catenin pathway in AS-BMSCs was higher than HV-BMSCs after osteogenic induction, while ILK overexpression further activated this axis. Besides, the osteogenic medium enhanced the nuclear translocation of β-catenin only in AS-BMSCs. Animal experiments revealed that the size and number of osteophytes progressively increased in a time-dependent manner in ankylosing enthesitis mice. Moreover, the expression of ILK in entheseal BMSCs was higher at week 24 and week 32 than at week 8, and this elevated expression positively correlated with osteophyte development. These findings indicate that increased ILK leads to excessive mineralization in AS-BMSCs via the activation of the Akt/GSK-3β/β-catenin pathway, resulting in ectopic ossification in AS patients.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"200 ","pages":"Article 117591"},"PeriodicalIF":3.5,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144651511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Large-scale proteomics analysis identifies plasma protein biomarkers and potential therapeutic targets for rheumatoid arthritis: A prospective study in UK Biobank","authors":"Xiaolei Ruan ,&nbsp;Lihe Zheng ,&nbsp;Yueming Dai ,&nbsp;Yingyi Li ,&nbsp;Ruowen Wang ,&nbsp;Guanhui Cai ,&nbsp;Wen Sun ,&nbsp;Yongyue Wei ,&nbsp;Yihong Zhang ,&nbsp;Hua Wang","doi":"10.1016/j.bone.2025.117593","DOIUrl":"10.1016/j.bone.2025.117593","url":null,"abstract":"<div><div>Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by symmetric joint swelling, pain, and progressive bone destruction. Although the advent of biologic therapies has significantly improved treatment outcomes, challenges remain in early detection and timely intervention. This study utilizes a nested case-cohort design from the UK Biobank (UKB), integrating proteomics, genome-wide association studies (GWAS), and single-cell RNA sequencing data from the GEO database to systematically evaluate proteins associated with RA risk and identify novel therapeutic targets. Through Cox analysis of proteomic data from 706 RA patients and 1410 controls, we identified 440 plasma proteins. Mendelian randomization analysis further narrowed down 35 plasma proteins, and colocalization analysis ultimately confirmed strong associations and colocalization for ICAM3, CTSV, and RNASET2 in the UKB-PPP dataset. Additionally, we developed an RA risk prediction model based on plasma proteins using the XGBoost algorithm, which demonstrated moderate performance (AUC = 0.74) with a prediction window of up to 5 years in advance. Furthermore, through functional enrichment analysis, protein-protein interaction (PPI) networks, and single-cell RNA sequencing, we elucidated the biological roles and mechanisms of these proteins in RA pathogenesis, providing new strategies for identifying biomarkers and developing targeted therapies for rheumatoid arthritis.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"200 ","pages":"Article 117593"},"PeriodicalIF":3.5,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144651512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}