Bone最新文献

{"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":"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}

{"title":"Effect of type 1 and type 2 diabetes on human femoral trabecular bone composition, microarchitecture, and mechanical behavior","authors":"Shannon R. Emerzian ,&nbsp;Jackson Hanlon ,&nbsp;Ramina Behzad ,&nbsp;Mustafa Unal ,&nbsp;Daniel J. Brooks ,&nbsp;I-Hsien Wu ,&nbsp;John Gauthier ,&nbsp;Surya Jangolla ,&nbsp;Marc Gregory Yu ,&nbsp;Hetal S. Shah ,&nbsp;George L. King ,&nbsp;Fjola Johannesdottir ,&nbsp;Lamya Karim ,&nbsp;Elaine W. Yu ,&nbsp;Mary L. Bouxsein","doi":"10.1016/j.bone.2025.117588","DOIUrl":"10.1016/j.bone.2025.117588","url":null,"abstract":"<div><div>Both type 1 diabetes (T1D) and type 2 diabetes (T2D) increase hip fracture risk beyond what bone mineral density (BMD) explains, potentially due to changes in bone material from advanced glycation end-products (AGEs) and altered matrix composition. However, there are limited data regarding the impact of diabetes on human trabecular bone composition and mechanical behavior.</div><div>We assessed trabecular bone material behavior using cadaveric femoral specimens from older adults with long-duration T1D (≥50 years; <em>n</em> = 24), T2D (<em>n</em> = 21), and non-diabetic controls (<em>n</em> = 21). Femoral head trabecular bone was evaluated via micro-computed tomography, mechanical testing (uniaxial compression), total fluorescent AGEs quantification, and Raman spectroscopy (matrix composition).</div><div>BMD and microarchitecture measures did not differ between groups (<em>p</em> &gt; 0.535). Compared to controls, T1D trabecular bone had higher AGE content (+42 %, <em>p</em> = 0.016), lower mineral-to-matrix ratio (−12 %, <em>p</em> = 0.048), trend toward lower crystallinity (−4 %, <em>p</em> = 0.054), and greater proline hydroxylation (+5 %, <em>p</em> = 0.007), but showed no differences in mechanical behavior (<em>p</em> ≥ 0.415). T2D trabecular bone also had elevated AGE (+60 %, <em>p</em> &lt; 0.001) and altered matrix composition. Unlike T1D, T2D bone demonstrated improved ductility and post-yield energy dissipation versus control, with greater ultimate strain (+36 %, <em>p</em> = 0.008), post-yield strain (+62 %, <em>p</em> = 0.075), and toughness to ultimate force (+38 %, <em>p</em> = 0.044).</div><div>This study reveals distinct effects of T1D and T2D on trabecular bone matrix composition, although these effects did not coincide with reduced mechanical properties under uniaxial compression loading.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"200 ","pages":"Article 117588"},"PeriodicalIF":3.5,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144632589","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":"Effect of load orientation on finite element strain predictions in a rabbit tibial loading model","authors":"Jonah M. Dimnik ,&nbsp;Andrew Sawatsky ,&nbsp;Roman J. Krawetz ,&nbsp;W. Brent Edwards","doi":"10.1016/j.bone.2025.117575","DOIUrl":"10.1016/j.bone.2025.117575","url":null,"abstract":"<div><div>Mechanical loading plays an important role in the maintenance of bone quantity and quality. Rodents are the most frequently used <em>in vivo</em> loading model for examining the relationship between applied mechanical loads and the bone adaptation response, but they do not naturally exhibit human-like intracortical remodeling. Instead, our group has developed a non-invasive <em>in vivo</em> rabbit tibial loading model. This study aimed to develop and validate statically equivalent computed tomography (CT)-based finite element (FE) models of the rabbit tibia to capture the micro-mechanical environment produced by our <em>in vivo</em> mechanical loading device. We further sought to investigate the strain prediction sensitivity to changes in the assumed force vector orientation. Twenty hindlimbs from New Zealand White Rabbits were cyclically loaded in uniaxial compression with strain gauge rosettes affixed to the tibia. The hindlimbs were then disarticulated at the hip, imaged with CT in replica experimental fixtures, and processed into specimen-specific FE models. A mathematical optimization routine was used to determine the individual force vector orientations that minimized the error between FE predicted and experimentally measured bone strains, which yielded highly accurate strain predictions (<span><math><mrow><msup><mrow><mi>R</mi></mrow><mrow><mn>2</mn></mrow></msup><mo>=</mo><mn>0</mn><mo>.</mo><mn>96</mn></mrow></math></span>) that exhibited a <span><math><mi>Y= X</mi></math></span> type of relationship after bias adjustment. This approach resulted in substantially lower strain prediction errors when compared to models using various single assumed orientation techniques. We also found that even slight deviations in the assumed hindlimb orientation substantially affect strain predictions. These findings suggest that experimentally informed approaches may be useful for hindlimb-specific loading orientations. This work serves to enable future studies examining the mechanobiology of bone adaptation using the rabbit animal model.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"200 ","pages":"Article 117575"},"PeriodicalIF":3.5,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144613872","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":"Efficacy of stem cell therapy for avascular necrosis of the femoral head: A systematic review and Meta-analysis","authors":"Saroj Kundan Bharti ,&nbsp;Mohammed Safeer V.S. ,&nbsp;Mannuru Venkateswarlu ,&nbsp;Mamidi Niveditha ,&nbsp;Sidharth Sharma ,&nbsp;Dipika Bansal","doi":"10.1016/j.bone.2025.117590","DOIUrl":"10.1016/j.bone.2025.117590","url":null,"abstract":"<div><h3>Background</h3><div>Osteonecrosis of the femoral head (ONFH) is a debilitating orthopaedic condition primarily affecting younger adults, often progressing to femoral head collapse and total hip replacement (THR). Stem cell therapy (SCT) has emerged as a regenerative option to delay disease progression and preserve joint function. This study aimed to evaluate efficacy of SCT, alone or in combination with mechanical support or bone grafting, in improving clinical outcomes in ONFH.</div></div><div><h3>Methods</h3><div>A comprehensive search was conducted up to November-2024. Randomized controlled trials (RCTs) comparing SCT with standard care in ONFH patients were included. Primary outcomes were THR incidence and disease progression; secondary outcomes included Harris Hip Score (HHS), Visual Analog Scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Data were pooled using random-effects models, and evidence certainty was assessed using the GRADE approach.</div></div><div><h3>Results</h3><div>Ten RCTs involving 545 hips were included, with overall mean follow-up duration across studies was 36 months. SCT, when used in combination with mechanical support or bone grafts, showed a trend towards reduced THR risk (RR: 0.74; 95 % CI: 0.46–1.20) and significantly improved functional outcomes (e.g., WOMAC MD: –10.7; 95 % CI: −17.2 to −4.3). Pure SCT alone did not yield statistically significant benefits across most outcomes. Subgroup analyses revealed that mechanical support notably enhanced the effect of SCT on HHS and THR prevention. The risk of bias was low in six studies and high in four. GRADE assessment rated the evidence as moderate for THR and low for other outcomes due to methodological limitations.</div></div><div><h3>Conclusion</h3><div>While pure SCT appears deceptive in ONFH treatment, its combined use with mechanical support or bone grafts might be promising.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"200 ","pages":"Article 117590"},"PeriodicalIF":3.5,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144621571","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":"Gastrointestinal complaints in patients with osteogenesis imperfecta: The bright side of a rare genetic disorder","authors":"Disha Sharma ,&nbsp;Gracia M. Viana Rodriguez ,&nbsp;Chunwei Walter Lai ,&nbsp;Bilal Asif ,&nbsp;Sara Talvacchio ,&nbsp;Alexander H. Yang ,&nbsp;Anusha Vittal ,&nbsp;Alberta Derkyi ,&nbsp;Christopher Koh ,&nbsp;Elizabeth C. Wright ,&nbsp;Joan C. Marini ,&nbsp;Theo Heller","doi":"10.1016/j.bone.2025.117589","DOIUrl":"10.1016/j.bone.2025.117589","url":null,"abstract":"<div><h3>Background</h3><div>Osteogenesis imperfecta (OI) is a rare hereditary disorder of connective tissue. A Danish national registry study surprisingly identified digestive causes as one of the leading causes of OI mortality. However, there is a dearth of prospective data describing gastrointestinal symptoms in OI. Our aim was to assess common gastrointestinal symptoms in an OI patient population and compare it to the general U.S. population.</div></div><div><h3>Methods</h3><div>OI patients enrolled in a natural history protocol (<span><span>NCT03575221</span><svg><path></path></svg></span>) were prospectively evaluated for gastrointestinal symptoms and provided with PROMIS questionnaires for six gastrointestinal symptoms. The HMSS application was used to obtain T scores, score of 50 (and standard deviation of 10) representing the average of the general U.S. population.</div></div><div><h3>Results</h3><div>41 OI patients were included. Median age 28 years (IQR 18–26), median BMI 28 kg/m² (IQR 21–34), and 54 % female. OI type IV 61 %, OI type III 20 %, and remaining patients had OI type VI, VII, XIV. The mean T score for the six gastrointestinal symptoms ranged from 46 to 49, within 1 SD from the general U.S. population. Subgroup analyses showed no differences based on age, mobility, BMI, type of OI and genetic mutations (<em>COL1A1</em> vs <em>COL1A2</em>), except increased abdominal pain with age. Patients with severe scoliosis (&gt;50°) reported increased nausea and vomiting, and diarrhea compared to patients with mild to moderate scoliosis.</div></div><div><h3>Discussion</h3><div>We report the largest cohort of OI patients evaluated prospectively and directly for gastrointestinal complaints. Study patients, which excluded type I OI, did not report gastrointestinal symptoms higher than the general population except for abdominal pain in older patients. OI patients should be carefully evaluated in the same way as any other patient presenting with gastrointestinal complaints.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"200 ","pages":"Article 117589"},"PeriodicalIF":3.5,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144621572","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":"Smpd3 regulates odontoblast differentiation through the Shh-Gli1 pathway","authors":"Catherine H. Chu ,&nbsp;Jiaohong Wang ,&nbsp;Chi Zhang ,&nbsp;Guoqing Li ,&nbsp;Lin Wang","doi":"10.1016/j.bone.2025.117587","DOIUrl":"10.1016/j.bone.2025.117587","url":null,"abstract":"<div><div>Teeth, like other ectodermal organs such as hair, skin, and sweat glands, are complex structures. Specifically, teeth are composed of four principal tissues: enamel, dentin, cementum, and pulp. Among these, dentin is a critical component, synthesized by odontoblasts—specialized cells derived from ectomesenchymal precursors originating in the neural crest. Odontoblasts are uniquely responsible for dentinogenesis, a process essential for tooth development and function. However, the molecular mechanisms regulating odontoblast differentiation remain poorly understood.</div><div>In this study, we first analyzed a public single-cell RNA sequencing data set of postnatal (PN1) mouse molars and found <em>Smpd3</em> as a potential gene of odontoblast differentiation. Then, we investigated the functional role of <em>Smpd3</em> in odontoblast differentiation using a combination of histological, molecular, and bioinformatics approaches. Knockdown of <em>Smpd3</em> expression <em>via</em> small interfering RNA (siRNA) significantly impaired odontoblast differentiation of mouse dental papilla cells (mDPCs), as evidenced by reductions in odontoblast-specific markers and mineralization. In contrast, overexpression of <em>Smpd3</em> enhanced odontogenic differentiation and increased mineralized nodule formation of mDPCs. To elucidate the underlying molecular mechanisms, bulk RNA sequencing was conducted, revealing that <em>Smpd3</em> is intricately linked to the Sonic Hedgehog (Shh) signaling pathway. <em>In vitro</em> studies and tooth germ culture were applied to validate the mechanism of <em>Smpd3</em> on odontoblast differentiation through the Shh-Gli1 pathway.</div><div>Mechanistically, we show that <em>Smpd3</em> upregulates dentinogenic markers (Dspp, Dmp1) in a Shh-dependent manner. <em>Smpd3</em> overexpression increased Shh pathway activity and promoted dentin formation <em>ex vivo</em>. This study highlights the critical role of <em>Smpd3</em> in tooth development and provides novel insights into the molecular regulation of dentinogenesis, offering potential therapeutic targets for methods that promote dentin regeneration when natural repairs are compromised.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"200 ","pages":"Article 117587"},"PeriodicalIF":3.5,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144610604","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":"Schip1 promotes osteoclast differentiation via Taok1-mediated activation of the p38 MAPK signaling pathway in mouse models of osteoporosis","authors":"Furui Liu ,&nbsp;Muhang Tian ,&nbsp;Sen Wang ,&nbsp;Lei Guo ,&nbsp;Fangjing Chen","doi":"10.1016/j.bone.2025.117579","DOIUrl":"10.1016/j.bone.2025.117579","url":null,"abstract":"<div><div>Schip1 serves as a pivotal regulatory factor in both the Hippo pathway and the PDGFB signaling pathway, which are significant in the pathogenesis of osteoporosis. However, the role of Schip1 in osteoporosis remains to be elucidated. In this study, we demonstrated for the first time that Schip1 acted as a positive regulator in osteoclastogenesis. We observed a significant upregulation of Schip1 expression during Rankl-induced osteoclast differentiation, and the suppression of Schip1 expression notably reduced Rankl-induced osteoclast formation. Functionally, Schip1 interacted with Taok1 to activate the p38 MAPK signaling pathway, which promoted osteoclast differentiation. Genetic ablation of Schip1 in mice resulted in pronounced osteosclerosis compared to wild-type controls. Furthermore, mice with deletion of Schip1 exhibited significantly mitigated osteoporosis following ovariectomy. Collectively, our findings establish Schip1 as a regulator of osteoclast differentiation and suggest its potential as a therapeutic target for osteoporosis.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"200 ","pages":"Article 117579"},"PeriodicalIF":3.5,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144581064","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}