首页 > 最新文献

Bone最新文献

英文 中文
Corrigendum to “Familial determinants of bone health parameters – a dual X-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT)-based parent and offspring study in rural Indian children” [Bone (2026), volume 202, article 117685] “骨骼健康参数的家族决定因素-基于印度农村儿童的双x射线吸收仪(DXA)和外围定量计算机断层扫描(pQCT)的父母和后代研究”的勘误表[骨(2026),第202卷,第117685条]。
IF 3.6 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-11-10 DOI: 10.1016/j.bone.2025.117707
Sharvani Patil , Nikhil Shah , Alex Ireland , Vivek Patwardhan , Neha Sanwalka , Neha Kajale , Chidvilas More , Ketan Gondhalekar , Anuradha Khadilkar
{"title":"Corrigendum to “Familial determinants of bone health parameters – a dual X-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT)-based parent and offspring study in rural Indian children” [Bone (2026), volume 202, article 117685]","authors":"Sharvani Patil , Nikhil Shah , Alex Ireland , Vivek Patwardhan , Neha Sanwalka , Neha Kajale , Chidvilas More , Ketan Gondhalekar , Anuradha Khadilkar","doi":"10.1016/j.bone.2025.117707","DOIUrl":"10.1016/j.bone.2025.117707","url":null,"abstract":"","PeriodicalId":9301,"journal":{"name":"Bone","volume":"203 ","pages":"Article 117707"},"PeriodicalIF":3.6,"publicationDate":"2025-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145491022","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}
引用次数: 0
Ethanol consumption has minimal effects on cancellous bone architecture in femur and lumbar vertebra in two species of non-human primates 乙醇消耗对两种非人灵长类动物股骨和腰椎的松质骨结构影响极小。
IF 3.6 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-11-09 DOI: 10.1016/j.bone.2025.117711
Alibek Zhakubayev , Kathleen A. Grant , Lara H. Sattgast , Russell T. Turner , Urszula T. Iwaniec , Mary Lauren Benton
Alcohol abuse is a risk factor for atraumatic fractures. Our previous work using a non-human primate model of voluntary ethanol consumption showed that chronic ethanol intake for 6 months to 2.5 years decreased global bone turnover and tibial cortical porosity but did not result in changes in distal tibia cancellous architecture. However, bone remodeling varies among skeletal sites. Here, we extended this analysis to include 3 additional cancellous bone compartments (distal femur metaphysis, distal femur epiphysis, lumbar vertebra). Specifically, we applied a machine learning framework to data from 155 monkeys (100 ethanol and 55 controls) to identify the bone features associated with chronic ethanol use. In concordance with our prior findings, we did not find that ethanol consumption resulted in population-level changes in cancellous bone architecture. These findings support the concept that ethanol consumption similarly decreases bone formation and bone resorption across sites, resulting in minimal changes in bone remodeling balance.
酗酒是造成非创伤性骨折的一个危险因素。我们之前使用非人类灵长类动物自愿乙醇消耗模型的研究表明,6 个月至2.5 年的慢性乙醇摄入会降低整体骨转换和胫骨皮质孔隙度,但不会导致胫骨远端松质结构的变化。然而,骨重塑在不同的骨骼部位是不同的。在这里,我们扩展了这一分析,包括3个额外的松质骨室(股骨远端干骺端、股骨远端骨骺、腰椎)。具体而言,我们将机器学习框架应用于155只猴子(100只乙醇和55只对照)的数据,以确定与慢性乙醇使用相关的骨骼特征。与我们之前的研究结果一致,我们没有发现乙醇消耗导致松质骨结构在人群水平上的变化。这些发现支持了乙醇消耗同样减少骨形成和骨吸收的概念,导致骨重塑平衡的最小变化。
{"title":"Ethanol consumption has minimal effects on cancellous bone architecture in femur and lumbar vertebra in two species of non-human primates","authors":"Alibek Zhakubayev ,&nbsp;Kathleen A. Grant ,&nbsp;Lara H. Sattgast ,&nbsp;Russell T. Turner ,&nbsp;Urszula T. Iwaniec ,&nbsp;Mary Lauren Benton","doi":"10.1016/j.bone.2025.117711","DOIUrl":"10.1016/j.bone.2025.117711","url":null,"abstract":"<div><div>Alcohol abuse is a risk factor for atraumatic fractures. Our previous work using a non-human primate model of voluntary ethanol consumption showed that chronic ethanol intake for 6 months to 2.5 years decreased global bone turnover and tibial cortical porosity but did not result in changes in distal tibia cancellous architecture. However, bone remodeling varies among skeletal sites. Here, we extended this analysis to include 3 additional cancellous bone compartments (distal femur metaphysis, distal femur epiphysis, lumbar vertebra). Specifically, we applied a machine learning framework to data from 155 monkeys (100 ethanol and 55 controls) to identify the bone features associated with chronic ethanol use. In concordance with our prior findings, we did not find that ethanol consumption resulted in population-level changes in cancellous bone architecture. These findings support the concept that ethanol consumption similarly decreases bone formation and bone resorption across sites, resulting in minimal changes in bone remodeling balance.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"203 ","pages":"Article 117711"},"PeriodicalIF":3.6,"publicationDate":"2025-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145497864","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}
引用次数: 0
Pediatric pQCT-derived tibial bone mineral density estimates: A systematic review and meta-regression 儿童pqct衍生胫骨骨密度估计:系统回顾和meta回归。
IF 3.6 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-11-08 DOI: 10.1016/j.bone.2025.117720
Anna Maria Markarian , Dennis R. Taaffe , Daniel A. Galvão , Jodie Cochrane Wilkie , Carolyn J. Peddle-McIntyre , Mark Markarian , Daniel J. Schiferl , Robert U. Newton

Background

Assessing bone mineral density (BMD) in children and adolescents is essential for detecting skeletal deficits and fracture risk. Peripheral quantitative computed tomography (pQCT) has gained increasing attention as a valuable imaging tool due to its ability to assess bone quality. Unlike dual-energy x-ray absorptiometry, pQCT provides volumetric BMD measurements and distinguishes between cortical and trabecular compartments. Despite these advantages, its clinical adoption remains limited due to the lack of reference data and standardized protocols.

Methods

A systematic search was conducted in CINAHL, Embase, PubMed, SPORTDiscus, and Web of Science from inception to November 2024. Studies reporting pQCT-derived tibial BMD in healthy children and adolescents (<19 years old) were included. Meta-regression models using natural cubic splines were applied to estimate age-specific BMD values for trabecular and cortical bone. Potential moderators, such as sex, race, reference line location, limb, and pQCT device, were evaluated to assess their influence on BMD outcomes.

Results

Eighty-three studies (18,531 participants) were included in this review. The meta-regression models demonstrated a non-linear relationship between BMD and age, best described using natural cubic splines. Moderator analysis indicated that sex, race, and reference line location significantly influenced cortical BMD, while trabecular BMD was affected by reference line location and pQCT device. The choice of limb assessed (dominant vs non-dominant) had minimal impact on BMD outcomes.

Conclusion

We present pQCT-derived BMD estimates from a diverse cohort of healthy children and adolescents and identify key moderators. Our findings provide a foundation for improved understanding and future standardization, laying the groundwork for enhancing the clinical utility of pQCT.
背景:评估儿童和青少年的骨密度(BMD)对于发现骨骼缺陷和骨折风险至关重要。外周定量计算机断层扫描(pQCT)作为一种有价值的成像工具,由于其评估骨质量的能力而受到越来越多的关注。与双能x线吸收仪不同,pQCT提供了体积骨密度测量,并区分了皮质和小梁间室。尽管有这些优势,但由于缺乏参考数据和标准化方案,其临床应用仍然有限。方法:系统检索CINAHL、Embase、PubMed、SPORTDiscus、Web of Science自建站至2024年11月。报告pqct衍生的健康儿童和青少年胫骨骨密度的研究(结果:83项研究(18,531名受试者)纳入本综述。meta回归模型显示BMD与年龄之间存在非线性关系,最好使用自然三次样条来描述。调节分析表明,性别、种族和参考线位置显著影响皮质骨密度,而参考线位置和pQCT设备影响小梁骨密度。评估肢体的选择(优势与非优势)对骨密度结果的影响最小。结论:我们从不同的健康儿童和青少年队列中提出了pqct衍生的BMD估计值,并确定了关键的调节因素。我们的研究结果为进一步了解和规范pQCT奠定了基础,为提高pQCT的临床应用奠定了基础。
{"title":"Pediatric pQCT-derived tibial bone mineral density estimates: A systematic review and meta-regression","authors":"Anna Maria Markarian ,&nbsp;Dennis R. Taaffe ,&nbsp;Daniel A. Galvão ,&nbsp;Jodie Cochrane Wilkie ,&nbsp;Carolyn J. Peddle-McIntyre ,&nbsp;Mark Markarian ,&nbsp;Daniel J. Schiferl ,&nbsp;Robert U. Newton","doi":"10.1016/j.bone.2025.117720","DOIUrl":"10.1016/j.bone.2025.117720","url":null,"abstract":"<div><h3>Background</h3><div>Assessing bone mineral density (BMD) in children and adolescents is essential for detecting skeletal deficits and fracture risk. Peripheral quantitative computed tomography (pQCT) has gained increasing attention as a valuable imaging tool due to its ability to assess bone quality. Unlike dual-energy x-ray absorptiometry, pQCT provides volumetric BMD measurements and distinguishes between cortical and trabecular compartments. Despite these advantages, its clinical adoption remains limited due to the lack of reference data and standardized protocols.</div></div><div><h3>Methods</h3><div>A systematic search was conducted in CINAHL, Embase, PubMed, SPORTDiscus, and Web of Science from inception to November 2024. Studies reporting pQCT-derived tibial BMD in healthy children and adolescents (&lt;19 years old) were included. Meta-regression models using natural cubic splines were applied to estimate age-specific BMD values for trabecular and cortical bone. Potential moderators, such as sex, race, reference line location, limb, and pQCT device, were evaluated to assess their influence on BMD outcomes.</div></div><div><h3>Results</h3><div>Eighty-three studies (18,531 participants) were included in this review. The meta-regression models demonstrated a non-linear relationship between BMD and age, best described using natural cubic splines. Moderator analysis indicated that sex, race, and reference line location significantly influenced cortical BMD, while trabecular BMD was affected by reference line location and pQCT device. The choice of limb assessed (dominant vs non-dominant) had minimal impact on BMD outcomes.</div></div><div><h3>Conclusion</h3><div>We present pQCT-derived BMD estimates from a diverse cohort of healthy children and adolescents and identify key moderators. Our findings provide a foundation for improved understanding and future standardization, laying the groundwork for enhancing the clinical utility of pQCT.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"203 ","pages":"Article 117720"},"PeriodicalIF":3.6,"publicationDate":"2025-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145484267","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}
引用次数: 0
Age-related response to 12-month romosozumab in treatment-naïve Japanese women aged 55–100 years with primary osteoporosis 年龄相关的12个月romosozumab对treatment-naïve日本女性55-100 岁原发性骨质疏松症的疗效
IF 3.6 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-11-06 DOI: 10.1016/j.bone.2025.117708
Takaomi Kobayashi , Tomonori Kobayakawa , Yukio Nakamura
This study aimed to investigate the age-related bone mineral density (BMD) response to romosozumab. A prospective cohort study was conducted on 221 treatment-naïve women aged 55–100 years with primary osteoporosis who initiated a 12-month romosozumab therapy. Percent changes in lumbar spine (LS), total hip (TH), and femoral neck (FN) BMD and bone turnover markers were assessed at 6 and 12 months. Associations between age and treatment efficacy were analyzed using multivariate regression, adjusting for potential confounders. Sensitivity analyses were conducted according to the baseline 25-hydroxyvitamin D (25OHD) status (<20 vs. ≥20 ng/mL). Restricted cubic spline curves were applied to assess the potential non-linear associations between age and the BMD response, adjusting for the same covariates. Multivariate regression showed that younger age is independently associated with higher percent changes in LS BMD at 6 (regression coefficient [β], −0.31; 95 % confidence interval [CI], −0.45 to −0.18) and 12 months (β, −0.19; 95 % CI, −0.36 to −0.02). Sensitivity analyses confirmed the association between age and percent gains in the LS BMD at 6 months but not at 12 months. No evidence of non-linearity was found at 6 (p for non-linearity = 0.874) and 12 months (p for non-linearity = 0.686). No significant associations were observed for TH or FN BMD or the bone turnover markers. An inverse linear relationship was observed between age and percent change of the LS BMD at 6 months; however, the relationship was not robust at 12 months.
本研究旨在探讨年龄相关的骨密度(BMD)对romosozumab的反应。一项前瞻性队列研究对221名年龄在55-100 岁的原发性骨质疏松症女性进行了为期12个月的romosozumab治疗。在6和12 个月时评估腰椎(LS)、全髋关节(TH)和股骨颈(FN)骨密度和骨转换标志物的百分比变化。使用多变量回归分析年龄与治疗效果之间的关系,调整潜在混杂因素。根据基线25-羟基维生素D (25OHD)状态进行敏感性分析(
{"title":"Age-related response to 12-month romosozumab in treatment-naïve Japanese women aged 55–100 years with primary osteoporosis","authors":"Takaomi Kobayashi ,&nbsp;Tomonori Kobayakawa ,&nbsp;Yukio Nakamura","doi":"10.1016/j.bone.2025.117708","DOIUrl":"10.1016/j.bone.2025.117708","url":null,"abstract":"<div><div>This study aimed to investigate the age-related bone mineral density (BMD) response to romosozumab. A prospective cohort study was conducted on 221 treatment-naïve women aged 55–100 years with primary osteoporosis who initiated a 12-month romosozumab therapy. Percent changes in lumbar spine (LS), total hip (TH), and femoral neck (FN) BMD and bone turnover markers were assessed at 6 and 12 months. Associations between age and treatment efficacy were analyzed using multivariate regression, adjusting for potential confounders. Sensitivity analyses were conducted according to the baseline 25-hydroxyvitamin D (25OHD) status (&lt;20 vs. ≥20 ng/mL). Restricted cubic spline curves were applied to assess the potential non-linear associations between age and the BMD response, adjusting for the same covariates. Multivariate regression showed that younger age is independently associated with higher percent changes in LS BMD at 6 (regression coefficient [<em>β</em>], −0.31; 95 % confidence interval [CI], −0.45 to −0.18) and 12 months (<em>β</em>, −0.19; 95 % CI, −0.36 to −0.02). Sensitivity analyses confirmed the association between age and percent gains in the LS BMD at 6 months but not at 12 months. No evidence of non-linearity was found at 6 (<em>p</em> for non-linearity = 0.874) and 12 months (<em>p</em> for non-linearity = 0.686). No significant associations were observed for TH or FN BMD or the bone turnover markers. An inverse linear relationship was observed between age and percent change of the LS BMD at 6 months; however, the relationship was not robust at 12 months.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"203 ","pages":"Article 117708"},"PeriodicalIF":3.6,"publicationDate":"2025-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145477112","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}
引用次数: 0
A comprehensive multi-layered analysis reveals genetic pleiotropy underlying coronary artery calcification and bone mineral density 一项全面的多层分析揭示了冠状动脉钙化和骨密度的遗传多效性。
IF 3.6 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-11-06 DOI: 10.1016/j.bone.2025.117719
Tao Han , Yang Qu , Jiangbo Zhu , Linna Sha , Bowen Lei , Rong Xiang , Xunying Zhao , Jiaojiao Hou , Qin Deng , Sirui Zheng , Jinyu Zhou , Ting Yu , Xin Song , Bin Yang , Yangdan Zhong , Maoyao Xia , Douglas P. Kiel , Xia Jiang

Objectives

Subclinical atherosclerosis and osteoporosis are often present together in the same individual, but their common mechanisms remain unclear. This study aims to investigate the pleiotropic relationship underlying coronary artery calcification (CAC) and estimated calcaneal bone mineral density (eBMD), providing molecular insights into their observed phenotypic associations.

Methods

Genetic correlation between CAC and eBMD was estimated based on genome-wide summary statistics. Shared loci were examined at the levels of single-nucleotide polymorphism (SNP), multi-SNP, and gene expressions to provide insights into genetic pleiotropy. Sensitivity analyses using data of DXA-derived BMD at femoral neck and lumbar spine were performed to validate key findings. Pathway enrichment analyses were conducted on significant shared loci to explore potential biological mechanisms.

Results

Despite an absence of a global genetic correlation, partitioning the genome into independent regions revealed five significant signals. Through subsequent multi-layered analysis, we identified 211 non-overlapping significant shared genes, including 190 from single-SNP-level, 27 from multi-SNP-level, and 3 from gene expression level, underscoring the widespread pleiotropy across CAC and eBMD. Notably, the shared signals were predominantly concentrated on chromosome 17, with SMG6 and PAFAH1B1 highlighted as crucial pleiotropic genes, and both were further confirmed by sensitivity analyses. Pathway enrichment analyses revealed oxidative stress regulation and the ubiquitin-proteasome system as critical biological mechanisms potentially linking the two traits.

Conclusion

Our study demonstrates that the observed association between CAC and eBMD is mainly driven by pleiotropic associations.
目的:亚临床动脉粥样硬化和骨质疏松常伴有,但其共同机制尚不清楚。本研究旨在探讨冠状动脉钙化(CAC)和跟骨骨密度(eBMD)之间的多效性关系,为观察到的表型关联提供分子见解。方法:基于全基因组汇总统计估计CAC与eBMD的遗传相关性。在单核苷酸多态性(SNP),多SNP和基因表达水平上检查共享位点,以提供遗传多效性的见解。利用dxa衍生的股骨颈和腰椎骨密度数据进行敏感性分析,以验证关键发现。对重要的共享位点进行通路富集分析,探索潜在的生物学机制。结果:尽管缺乏全局遗传相关性,但将基因组划分为独立区域揭示了五个重要信号。通过随后的多层分析,我们确定了211个非重叠的重要共享基因,其中190个来自单snp水平,27个来自多snp水平,3个来自基因表达水平,强调了CAC和eBMD中广泛存在的多效性。值得注意的是,共享信号主要集中在17号染色体上,SMG6和PAFAH1B1被强调为关键的多效性基因,这两个基因都被敏感性分析进一步证实。途径富集分析显示,氧化应激调节和泛素-蛋白酶体系统可能是连接这两个性状的关键生物学机制。结论:我们的研究表明,CAC与eBMD之间的关联主要是由多效性关联驱动的。
{"title":"A comprehensive multi-layered analysis reveals genetic pleiotropy underlying coronary artery calcification and bone mineral density","authors":"Tao Han ,&nbsp;Yang Qu ,&nbsp;Jiangbo Zhu ,&nbsp;Linna Sha ,&nbsp;Bowen Lei ,&nbsp;Rong Xiang ,&nbsp;Xunying Zhao ,&nbsp;Jiaojiao Hou ,&nbsp;Qin Deng ,&nbsp;Sirui Zheng ,&nbsp;Jinyu Zhou ,&nbsp;Ting Yu ,&nbsp;Xin Song ,&nbsp;Bin Yang ,&nbsp;Yangdan Zhong ,&nbsp;Maoyao Xia ,&nbsp;Douglas P. Kiel ,&nbsp;Xia Jiang","doi":"10.1016/j.bone.2025.117719","DOIUrl":"10.1016/j.bone.2025.117719","url":null,"abstract":"<div><h3>Objectives</h3><div>Subclinical atherosclerosis and osteoporosis are often present together in the same individual, but their common mechanisms remain unclear. This study aims to investigate the pleiotropic relationship underlying coronary artery calcification (CAC) and estimated calcaneal bone mineral density (eBMD), providing molecular insights into their observed phenotypic associations.</div></div><div><h3>Methods</h3><div>Genetic correlation between CAC and eBMD was estimated based on genome-wide summary statistics. Shared loci were examined at the levels of single-nucleotide polymorphism (SNP), multi-SNP, and gene expressions to provide insights into genetic pleiotropy. Sensitivity analyses using data of DXA-derived BMD at femoral neck and lumbar spine were performed to validate key findings. Pathway enrichment analyses were conducted on significant shared loci to explore potential biological mechanisms.</div></div><div><h3>Results</h3><div>Despite an absence of a global genetic correlation, partitioning the genome into independent regions revealed five significant signals. Through subsequent multi-layered analysis, we identified 211 non-overlapping significant shared genes, including 190 from single-SNP-level, 27 from multi-SNP-level, and 3 from gene expression level, underscoring the widespread pleiotropy across CAC and eBMD. Notably, the shared signals were predominantly concentrated on chromosome 17, with <em>SMG6</em> and <em>PAFAH1B1</em> highlighted as crucial pleiotropic genes, and both were further confirmed by sensitivity analyses. Pathway enrichment analyses revealed oxidative stress regulation and the ubiquitin-proteasome system as critical biological mechanisms potentially linking the two traits.</div></div><div><h3>Conclusion</h3><div>Our study demonstrates that the observed association between CAC and eBMD is mainly driven by pleiotropic associations.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"203 ","pages":"Article 117719"},"PeriodicalIF":3.6,"publicationDate":"2025-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145476841","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}
引用次数: 0
Angiotensin receptor blockers (ARBs) but not angiotensin converting enzyme inhibitors (ACE-Is) are associated with lower osteoclast activity and higher bone mineral density: Results from the TUDA study 来自TUDA研究的结果显示,血管紧张素受体阻滞剂(ARBs)而非血管紧张素转换酶抑制剂(ACE-Is)与破骨细胞活性降低和骨密度升高相关
IF 3.6 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-11-05 DOI: 10.1016/j.bone.2025.117710
Donal Fitzpatrick , Eamon Laird , Mary Ward , Leane Hoey , Catherine F. Hughes , Liadhan McAnena , J.J. Strain , Conal Cunningham , Anne M. Molloy , Helene McNulty , Rosaleen Lannon , Kevin McCarroll

Introduction

The renin-angiotensin system (RAS) is implicated in osteoclast activation and bone loss. We investigated the relationship of angiotensin receptor blockers (ARBs) or angiotensin-converting enzyme inhibitors (ACE-Is) usage with bone turnover markers (BTM) and bone mineral density (BMD).

Methods

Participants were from the TUDA cohort of Irish adults aged ≥60 years not receiving osteoporosis treatment. BMD at the total hip, femoral neck and lumbar spine, and BTMs were compared between users of ARBs or ACE-Is and non-users of either medication, adjusting for age, sex, BMI, Timed-Up-and-Go, vitamin D status, eGFR, parathyroid hormone, lifestyle factors, socioeconomic status, comorbidities and other medications.

Results

In the ARB analysis (n = 1516; mean age 70.2 years; 64 % female; 33 % users), ARB use vs non-use was associated with higher adjusted BMD at the femoral neck 0.856 g/cm2 (95 % CI 0.830–0.882) vs 0.837 (0.812–0.863), p = 0.005; total hip 0.937 g/cm2 (0.909–0.965) vs 0.913 (0.886–0.941), p = 0.002; and lumbar spine 1.122 g/cm2 (1.082–1.162) vs 1.087 (1.047–1.126), p < 0.001. In the ACE-I analysis (n = 1692; mean age 70.1 years; 59 % female; 40 % users), ACE-I usage was not associated with BMD. In a subsample with available BTM (n = 1613), ARB users versus non-users had lower serum adjusted tartrate-resistant acid phosphatase 3.14 units/l (2.87–3.41) vs 3.28 (3.01–3.55), p = 0.040. No association was found between ACE-I usage and TRACP5b.

Discussion

ARB use was associated with higher BMD and lower TRACP5b, a marker of osteoclast activity, with no corresponding associations for ACE-Is. This pattern suggests a possible differential effect between ARBs and ACE-Is on bone that merits evaluation in prospective cohorts and randomised trials.
肾素-血管紧张素系统(RAS)与破骨细胞活化和骨质流失有关。我们研究了血管紧张素受体阻滞剂(ARBs)或血管紧张素转换酶抑制剂(ACE-Is)的使用与骨转换标志物(BTM)和骨矿物质密度(BMD)的关系。方法参与者来自TUDA队列,年龄≥60岁,未接受骨质疏松治疗的爱尔兰成年人。在调整年龄、性别、BMI、time - upand - go、维生素D状态、eGFR、甲状旁腺激素、生活方式因素、社会经济状况、合并症和其他药物后,比较arb或ACE-Is使用者与非arb或ACE-Is使用者的全髋关节、股骨颈和腰椎的骨密度以及btm。结果在ARB分析中(n = 1516例,平均年龄70.2岁,女性占64%,使用ARB者占33%),使用ARB者与不使用ARB者股骨颈校正骨密度较高(0.856 g/cm2)相关(95% CI 0.830-0.882) vs 0.837 (0.812-0.863), p = 0.005;总臀围0.937 g/cm2 (0.909-0.965) vs 0.913 (0.886-0.941), p = 0.002;腰椎1.122 g/cm2 (1.082-1.162) vs 1.087 (1.047-1.126), p < 0.001。在ACE-I分析中(n = 1692,平均年龄70.1岁,59%为女性,40%为使用者),ACE-I的使用与BMD无关。在具有可用BTM的子样本中(n = 1613), ARB使用者与非使用者的血清调整酒石酸耐受性酸性磷酸酶较低,分别为3.14单位/升(2.87-3.41)和3.28单位/升(3.01-3.55),p = 0.040。ACE-I的使用与TRACP5b之间没有关联。arb的使用与较高的骨密度和较低的TRACP5b(一种破骨细胞活性的标志物)相关,而与ACE-Is没有相应的关联。这种模式表明arb和ACE-Is对骨骼可能有不同的影响,值得在前瞻性队列和随机试验中进行评估。
{"title":"Angiotensin receptor blockers (ARBs) but not angiotensin converting enzyme inhibitors (ACE-Is) are associated with lower osteoclast activity and higher bone mineral density: Results from the TUDA study","authors":"Donal Fitzpatrick ,&nbsp;Eamon Laird ,&nbsp;Mary Ward ,&nbsp;Leane Hoey ,&nbsp;Catherine F. Hughes ,&nbsp;Liadhan McAnena ,&nbsp;J.J. Strain ,&nbsp;Conal Cunningham ,&nbsp;Anne M. Molloy ,&nbsp;Helene McNulty ,&nbsp;Rosaleen Lannon ,&nbsp;Kevin McCarroll","doi":"10.1016/j.bone.2025.117710","DOIUrl":"10.1016/j.bone.2025.117710","url":null,"abstract":"<div><h3>Introduction</h3><div>The renin-angiotensin system (RAS) is implicated in osteoclast activation and bone loss. We investigated the relationship of angiotensin receptor blockers (ARBs) or angiotensin-converting enzyme inhibitors (ACE-Is) usage with bone turnover markers (BTM) and bone mineral density (BMD).</div></div><div><h3>Methods</h3><div>Participants were from the TUDA cohort of Irish adults aged ≥60 years not receiving osteoporosis treatment. BMD at the total hip, femoral neck and lumbar spine, and BTMs were compared between users of ARBs or ACE-Is and non-users of either medication, adjusting for age, sex, BMI, Timed-Up-and-Go, vitamin D status, eGFR, parathyroid hormone, lifestyle factors, socioeconomic status, comorbidities and other medications.</div></div><div><h3>Results</h3><div>In the ARB analysis (<em>n</em> = 1516; mean age 70.2 years; 64 % female; 33 % users), ARB use vs non-use was associated with higher adjusted BMD at the femoral neck 0.856 g/cm<sup>2</sup> (95 % CI 0.830–0.882) vs 0.837 (0.812–0.863), <em>p</em> = 0.005; total hip 0.937 g/cm<sup>2</sup> (0.909–0.965) vs 0.913 (0.886–0.941), <em>p</em> = 0.002; and lumbar spine 1.122 g/cm<sup>2</sup> (1.082–1.162) vs 1.087 (1.047–1.126), <em>p</em> &lt; 0.001. In the ACE-I analysis (<em>n</em> = 1692; mean age 70.1 years; 59 % female; 40 % users), ACE-I usage was not associated with BMD. In a subsample with available BTM (<em>n</em> = 1613), ARB users versus non-users had lower serum adjusted tartrate-resistant acid phosphatase 3.14 units/l (2.87–3.41) vs 3.28 (3.01–3.55), <em>p</em> = 0.040. No association was found between ACE-I usage and TRACP5b.</div></div><div><h3>Discussion</h3><div>ARB use was associated with higher BMD and lower TRACP5b, a marker of osteoclast activity, with no corresponding associations for ACE-Is. This pattern suggests a possible differential effect between ARBs and ACE-Is on bone that merits evaluation in prospective cohorts and randomised trials.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"203 ","pages":"Article 117710"},"PeriodicalIF":3.6,"publicationDate":"2025-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145464740","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}
引用次数: 0
Corrigendum to “Comparing bone and muscle parameters in community-dwelling older adults with obesity, with or without type 2 diabetes mellitus” [Bone 202 (2026) 117680] “比较有或没有2型糖尿病的老年肥胖社区居民的骨骼和肌肉参数”的勘误表[骨202(2026)117680]。
IF 3.6 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-11-05 DOI: 10.1016/j.bone.2025.117706
Costas Glavas , Jakub Mesinovic , Peter R. Ebeling , Surbhi Sood , Elena S. George , Melkamu Tamir Hunegnaw , Ayse Zengin , Robin M. Daly , Paul Jansons , David Scott
{"title":"Corrigendum to “Comparing bone and muscle parameters in community-dwelling older adults with obesity, with or without type 2 diabetes mellitus” [Bone 202 (2026) 117680]","authors":"Costas Glavas ,&nbsp;Jakub Mesinovic ,&nbsp;Peter R. Ebeling ,&nbsp;Surbhi Sood ,&nbsp;Elena S. George ,&nbsp;Melkamu Tamir Hunegnaw ,&nbsp;Ayse Zengin ,&nbsp;Robin M. Daly ,&nbsp;Paul Jansons ,&nbsp;David Scott","doi":"10.1016/j.bone.2025.117706","DOIUrl":"10.1016/j.bone.2025.117706","url":null,"abstract":"","PeriodicalId":9301,"journal":{"name":"Bone","volume":"202 ","pages":"Article 117706"},"PeriodicalIF":3.6,"publicationDate":"2025-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145454190","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}
引用次数: 0
Bone size and sex are key determinants of the longitudinal bone phenotype trajectory in aging males and females 骨大小和性别是衰老男性和女性纵向骨表型轨迹的关键决定因素。
IF 3.6 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-11-04 DOI: 10.1016/j.bone.2025.117709
Annabel R. Bugbird , Lauren A. Burt , Danielle E. Whittier , Steven K. Boyd
<div><h3>Introduction:</h3><div>A previously developed <em>phenotyping</em> model groups common combinations of bone characteristics into three primary phenotypes: <em>healthy</em>, <em>low volume</em>, and <em>low density</em> from high resolution peripheral quantitative computed tomography (HR-pQCT). While these phenotypes have been characterized in cross-sectional cohorts, their longitudinal progression and transitions with aging remains unknown. Therefore, the aim of this study was to investigate how bone microarchitecture phenotypes evolves over time, identify common transitional patterns, and examine their association with fracture risk.</div></div><div><h3>Methods:</h3><div>Our cohort included 606 adult male and female participants from a longitudinal population study. HR-pQCT scans of the distal radius and tibia were acquired at two visits. Bone phenotypes, defined as <em>healthy</em>, <em>low volume</em>, and <em>low density</em>, were determined at baseline and follow-up. Transitional patterns in phenotypes were examined by age group and sex, and further analyzed in relation to average bone size based on cross-sectional area. The relative contributions of sex and bone size to phenotype transitions were evaluated using nested linear regression models.</div></div><div><h3>Results:</h3><div>The average age of participants was 60.4 ± 16.2 years, with a mean follow-up duration of 6.76 ± 1.78 years. Phenotype membership remained relatively stable over the follow-up time but exhibited an average transitional pattern from the <em>healthy</em> phenotype in younger adults (18–40 years), to <em>low volume</em> (40–60 years), and eventually to <em>low density</em> (60+ years), particularly among females. When stratified by bone size, individuals with larger bones tended to follow an average trajectory from <em>healthy</em> to <em>low density</em>, whereas those with smaller bones typically transitioned from <em>healthy</em> to <em>low volume</em> to <em>low density</em>. Although sex and bone size were strongly correlated (R<span><math><mrow><msup><mrow></mrow><mrow><mn>2</mn></mrow></msup><mo>=</mo></mrow></math></span> 0.43), and showed similar transitional patterns, sex remained a significant predictor of phenotype membership even after adjusting for bone size (p <span><math><mo><</mo></math></span> 0.001).</div></div><div><h3>Conclusion:</h3><div>These findings demonstrate that the bone phenotype model provides a dynamic, interpretable framework for monitoring skeletal health over time, capturing age-, sex-, and size-related trajectories, and offering potential for individualized bone health assessment.</div></div><div><h3>Lay Summary:</h3><div>We investigated the longitudinal progression of bone phenotypes, categorized as <em>healthy</em>, <em>low volume</em>, and <em>low density</em>, in adult males and females. Phenotype transitions were analyzed by age, sex, and average bone size. Most individuals followed an average trajectory from <em>
先前开发的表型模型将骨骼特征的常见组合分为三种主要表型:高分辨率外周定量计算机断层扫描(HR-pQCT)的健康,低体积和低密度。虽然这些表型已经在横断面队列中被表征,但它们的纵向进展和随年龄的转变仍然未知。因此,本研究的目的是研究骨微结构表型如何随时间演变,确定常见的过渡模式,并检查它们与骨折风险的关系。方法:我们的队列包括来自纵向人口研究的606名成年男性和女性参与者。在两次访问中获得了远端桡骨和胫骨的HR-pQCT扫描。在基线和随访时确定骨表型,定义为健康,低体积和低密度。表型的过渡模式按年龄组和性别进行检查,并进一步分析与基于横截面积的平均骨大小的关系。使用嵌套线性回归模型评估性别和骨大小对表型转变的相对贡献。结果:参与者平均年龄为60.4±16.2岁,平均随访时间为6.76±1.78年。在随访期间,表型成员保持相对稳定,但表现出从年轻成人(18-40岁)的健康表型到低体积(40-60岁),最终到低密度(60岁以上)的平均过渡模式,特别是在女性中。当按骨骼大小分层时,骨骼较大的个体往往遵循从健康到低密度的平均轨迹,而骨骼较小的个体通常从健康到低体积再到低密度。尽管性别和骨大小密切相关(R2=0.43),并且表现出相似的过渡模式,性别仍然是表型成员的重要预测因子,即使在调整骨大小后(p < 0.001)。结论:这些发现表明,骨表型模型提供了一个动态的、可解释的框架,用于监测骨骼健康随时间的变化,捕捉年龄、性别和尺寸相关的轨迹,并提供个性化骨骼健康评估的潜力。概要:我们研究了成年男性和女性骨骼表型的纵向进展,分类为健康、低体积和低密度。表型转变按年龄、性别和平均骨大小进行分析。大多数个体遵循从健康到低体积再到低密度的平均轨迹,骨折风险从低体积到低密度显著增加。较大的骨骼往往会跳过低体积阶段,直接过渡到低密度阶段。研究结果表明,骨表型在个体化骨健康评估中的潜力。
{"title":"Bone size and sex are key determinants of the longitudinal bone phenotype trajectory in aging males and females","authors":"Annabel R. Bugbird ,&nbsp;Lauren A. Burt ,&nbsp;Danielle E. Whittier ,&nbsp;Steven K. Boyd","doi":"10.1016/j.bone.2025.117709","DOIUrl":"10.1016/j.bone.2025.117709","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Introduction:&lt;/h3&gt;&lt;div&gt;A previously developed &lt;em&gt;phenotyping&lt;/em&gt; model groups common combinations of bone characteristics into three primary phenotypes: &lt;em&gt;healthy&lt;/em&gt;, &lt;em&gt;low volume&lt;/em&gt;, and &lt;em&gt;low density&lt;/em&gt; from high resolution peripheral quantitative computed tomography (HR-pQCT). While these phenotypes have been characterized in cross-sectional cohorts, their longitudinal progression and transitions with aging remains unknown. Therefore, the aim of this study was to investigate how bone microarchitecture phenotypes evolves over time, identify common transitional patterns, and examine their association with fracture risk.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods:&lt;/h3&gt;&lt;div&gt;Our cohort included 606 adult male and female participants from a longitudinal population study. HR-pQCT scans of the distal radius and tibia were acquired at two visits. Bone phenotypes, defined as &lt;em&gt;healthy&lt;/em&gt;, &lt;em&gt;low volume&lt;/em&gt;, and &lt;em&gt;low density&lt;/em&gt;, were determined at baseline and follow-up. Transitional patterns in phenotypes were examined by age group and sex, and further analyzed in relation to average bone size based on cross-sectional area. The relative contributions of sex and bone size to phenotype transitions were evaluated using nested linear regression models.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results:&lt;/h3&gt;&lt;div&gt;The average age of participants was 60.4 ± 16.2 years, with a mean follow-up duration of 6.76 ± 1.78 years. Phenotype membership remained relatively stable over the follow-up time but exhibited an average transitional pattern from the &lt;em&gt;healthy&lt;/em&gt; phenotype in younger adults (18–40 years), to &lt;em&gt;low volume&lt;/em&gt; (40–60 years), and eventually to &lt;em&gt;low density&lt;/em&gt; (60+ years), particularly among females. When stratified by bone size, individuals with larger bones tended to follow an average trajectory from &lt;em&gt;healthy&lt;/em&gt; to &lt;em&gt;low density&lt;/em&gt;, whereas those with smaller bones typically transitioned from &lt;em&gt;healthy&lt;/em&gt; to &lt;em&gt;low volume&lt;/em&gt; to &lt;em&gt;low density&lt;/em&gt;. Although sex and bone size were strongly correlated (R&lt;span&gt;&lt;math&gt;&lt;mrow&gt;&lt;msup&gt;&lt;mrow&gt;&lt;/mrow&gt;&lt;mrow&gt;&lt;mn&gt;2&lt;/mn&gt;&lt;/mrow&gt;&lt;/msup&gt;&lt;mo&gt;=&lt;/mo&gt;&lt;/mrow&gt;&lt;/math&gt;&lt;/span&gt; 0.43), and showed similar transitional patterns, sex remained a significant predictor of phenotype membership even after adjusting for bone size (p &lt;span&gt;&lt;math&gt;&lt;mo&gt;&lt;&lt;/mo&gt;&lt;/math&gt;&lt;/span&gt; 0.001).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion:&lt;/h3&gt;&lt;div&gt;These findings demonstrate that the bone phenotype model provides a dynamic, interpretable framework for monitoring skeletal health over time, capturing age-, sex-, and size-related trajectories, and offering potential for individualized bone health assessment.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Lay Summary:&lt;/h3&gt;&lt;div&gt;We investigated the longitudinal progression of bone phenotypes, categorized as &lt;em&gt;healthy&lt;/em&gt;, &lt;em&gt;low volume&lt;/em&gt;, and &lt;em&gt;low density&lt;/em&gt;, in adult males and females. Phenotype transitions were analyzed by age, sex, and average bone size. Most individuals followed an average trajectory from &lt;em&gt;","PeriodicalId":9301,"journal":{"name":"Bone","volume":"203 ","pages":"Article 117709"},"PeriodicalIF":3.6,"publicationDate":"2025-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145460844","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}
引用次数: 0
Response to ‘reconsidering bone-muscle interactions in obese older adults with type 2 diabetes: Methodological limitations and future directions’ 对“重新考虑肥胖老年2型糖尿病患者骨骼肌相互作用:方法学局限性和未来方向”的回应。
IF 3.6 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-11-04 DOI: 10.1016/j.bone.2025.117700
Costas Glavas , Jakub Mesinovic , Peter R. Ebeling , Surbhi Sood , Elena S. George , Melkamu Tamir Hunegnaw , Ayse Zengin , Robin M. Daly , Paul Jansons , David Scott
{"title":"Response to ‘reconsidering bone-muscle interactions in obese older adults with type 2 diabetes: Methodological limitations and future directions’","authors":"Costas Glavas ,&nbsp;Jakub Mesinovic ,&nbsp;Peter R. Ebeling ,&nbsp;Surbhi Sood ,&nbsp;Elena S. George ,&nbsp;Melkamu Tamir Hunegnaw ,&nbsp;Ayse Zengin ,&nbsp;Robin M. Daly ,&nbsp;Paul Jansons ,&nbsp;David Scott","doi":"10.1016/j.bone.2025.117700","DOIUrl":"10.1016/j.bone.2025.117700","url":null,"abstract":"","PeriodicalId":9301,"journal":{"name":"Bone","volume":"203 ","pages":"Article 117700"},"PeriodicalIF":3.6,"publicationDate":"2025-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145460842","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}
引用次数: 0
Melatonin promotes osteogenic differentiation of BMSCs by regulating circZFAND1/miR-433-3p/DKK1 pathway through melatonin receptor-dependent m6A modification of circZFAND1 褪黑激素通过褪黑激素受体依赖的m6A修饰circZFAND1,调节circZFAND1/miR-433-3p/DKK1通路,促进BMSCs成骨分化。
IF 3.6 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-11-03 DOI: 10.1016/j.bone.2025.117691
Yubo Shi , Jianzhou Yu , Yanqing Wu , Hao Fang , Bo Yang
An effective approach for treating osteoporosis (OP) is to focus on restoring the osteogenic ability of bone marrow-derived mesenchymal stem cells (BMSCs). Melatonin (MEL) has been found to possess the capability to enhance osteogenesis. Nevertheless, the precise mechanisms through which MEL regulates the differentiation of BMSCs and the development of OP are still not well understood. In the present study, circZFAND1 characterization was validated using Sanger sequencing, RNase R treatment, and RNA fluorescence in situ hybridization assay. To investigate the relationship between circZFAND1, DKK1 and miR-433-3p, we performed a series of experiments including the luciferase reporter assay, RNA immunoprecipitation assay, and rescue experiments. In addition, the MEL-mediated m6A modification of circZFAND1 was evaluated using dot-blot assay and Methylated RNA immunoprecipitation (Me-RIP) assay. Finally, the osteogenic differentiation of BMSCs was detected through function assays, including immunofluorescence staining, 5-ethynyl-20-deoxyuridine (EdU) assay, western blotting, and staining with alkaline phosphatase and alizarin red. The results showed that MEL promoted osteogenic differentiation of BMSCs by regulating circZFAND1/miR-433-3p/DKK1 pathway through melatonin receptor 2 (MT2) -dependent m6A modification of circZFAND1. These findings offer novel biomarkers for managing OP and may lay the theoretical foundation for applying MEL for OP management in the clinical setting.
修复骨髓间充质干细胞(BMSCs)的成骨能力是治疗骨质疏松症(OP)的有效途径。褪黑素(MEL)已被发现具有促进成骨的能力。然而,MEL调控骨髓间充质干细胞分化和OP形成的确切机制尚不清楚。在本研究中,通过Sanger测序、RNase R处理和RNA荧光原位杂交试验验证了circZFAND1的特性。为了研究circZFAND1、DKK1与miR-433-3p之间的关系,我们进行了一系列实验,包括荧光素酶报告基因实验、RNA免疫沉淀实验和拯救实验。此外,使用点印迹法和甲基化RNA免疫沉淀(Me-RIP)法评估mel介导的circZFAND1的m6A修饰。最后,通过免疫荧光染色、5-乙基-20-脱氧尿苷(EdU)法、western blot、碱性磷酸酶和茜素红染色等功能检测骨髓间充质干细胞的成骨分化。结果表明,MEL通过褪黑激素受体2 (MT2)依赖性m6A修饰circZFAND1,调控circZFAND1/miR-433-3p/DKK1通路,促进BMSCs成骨分化。这些发现为治疗OP提供了新的生物标志物,并可能为MEL在临床应用于OP管理奠定理论基础。
{"title":"Melatonin promotes osteogenic differentiation of BMSCs by regulating circZFAND1/miR-433-3p/DKK1 pathway through melatonin receptor-dependent m6A modification of circZFAND1","authors":"Yubo Shi ,&nbsp;Jianzhou Yu ,&nbsp;Yanqing Wu ,&nbsp;Hao Fang ,&nbsp;Bo Yang","doi":"10.1016/j.bone.2025.117691","DOIUrl":"10.1016/j.bone.2025.117691","url":null,"abstract":"<div><div>An effective approach for treating osteoporosis (OP) is to focus on restoring the osteogenic ability of bone marrow-derived mesenchymal stem cells (BMSCs). Melatonin (MEL) has been found to possess the capability to enhance osteogenesis. Nevertheless, the precise mechanisms through which MEL regulates the differentiation of BMSCs and the development of OP are still not well understood. In the present study, circZFAND1 characterization was validated using Sanger sequencing, RNase R treatment, and RNA fluorescence in situ hybridization assay. To investigate the relationship between circZFAND1, DKK1 and miR-433-3p, we performed a series of experiments including the luciferase reporter assay, RNA immunoprecipitation assay, and rescue experiments. In addition, the MEL-mediated m6A modification of circZFAND1 was evaluated using dot-blot assay and Methylated RNA immunoprecipitation (Me-RIP) assay. Finally, the osteogenic differentiation of BMSCs was detected through function assays, including immunofluorescence staining, 5-ethynyl-20-deoxyuridine (EdU) assay, western blotting, and staining with alkaline phosphatase and alizarin red. The results showed that MEL promoted osteogenic differentiation of BMSCs by regulating circZFAND1/miR-433-3p/DKK1 pathway through melatonin receptor 2 (MT2) -dependent m6A modification of circZFAND1. These findings offer novel biomarkers for managing OP and may lay the theoretical foundation for applying MEL for OP management in the clinical setting.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"202 ","pages":"Article 117691"},"PeriodicalIF":3.6,"publicationDate":"2025-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145454174","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}
引用次数: 0
期刊
Bone
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1