Bone最新文献

{"title":"Association of body fat distribution with bone mineral density: evidence from observational and mendelian randomization analyses","authors":"Qichao Sun ,&nbsp;Lijia Cui ,&nbsp;Yuxi Liu ,&nbsp;Qianqian Pang ,&nbsp;Yue Chi ,&nbsp;Ruizhi Jiajue ,&nbsp;Wei Liu ,&nbsp;Yan Jiang ,&nbsp;Ou Wang ,&nbsp;Mei Li ,&nbsp;Xiaoping Xing ,&nbsp;Weibo Xia","doi":"10.1016/j.bone.2025.117742","DOIUrl":"10.1016/j.bone.2025.117742","url":null,"abstract":"<div><h3>Background</h3><div>Although higher body weight is generally considered protective against low bone mineral density (BMD), the influence of body fat distribution on BMD remains unclear. We aimed to investigate whether specific adipose tissue depots have differential associations with BMD and to assess causality using Mendelian randomization (MR).</div></div><div><h3>Methods</h3><div>We conducted a cross-sectional analysis using National Health and Nutrition Examination Survey (NHANES) data to evaluate associations between regional fat depots (gynoid, android, visceral, abdominal subcutaneous fat, and total fat percentage) and BMD at total body, femoral neck, and lumbar spine. Multivariable linear regression was used to evaluate these relationships. To assess potential causal effects, we performed two-sample MR using genome-wide association study summary statistics for fat distribution traits and BMD.</div></div><div><h3>Results</h3><div>Gynoid fat was positively associated with BMD at the total body, femoral neck, and lumbar spine, while visceral and total body fat showed consistent inverse associations across these regions. Two-sample MR analysis supported a causal effect of gynoid fat on BMD but found no evidence of causality for visceral or total body fat.</div></div><div><h3>Conclusions</h3><div>Gynoid fat shows a beneficial and causal effect on BMD, whereas the inverse associations observed for visceral and total body fat appear to be non-causal. These findings underscore the importance of considering fat distribution, not merely total body fat or weight, when evaluating bone health.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"204 ","pages":"Article 117742"},"PeriodicalIF":3.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145746148","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 “LIPUS promotes osteogenesis via the mcirc_9393-miR-217/326-SIRT1 axis in porous Ti6Al4V scaffolds” [Bone 201 (2025) 117647]","authors":"Hongjuan Cao ,&nbsp;Yue Yu ,&nbsp;Lin Wu ,&nbsp;Fengyu Hao","doi":"10.1016/j.bone.2025.117766","DOIUrl":"10.1016/j.bone.2025.117766","url":null,"abstract":"","PeriodicalId":9301,"journal":{"name":"Bone","volume":"204 ","pages":"Article 117766"},"PeriodicalIF":3.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145822360","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 bisphosphonate treatment on the oim mouse middle ear ossicles' structure, composition and hearing","authors":"Maialen Ugarteburu ,&nbsp;Michael Doube ,&nbsp;Christoph Rau ,&nbsp;Olga Antipova ,&nbsp;Lu Xi Li ,&nbsp;Stuart R. Stock ,&nbsp;Xiaodong Tan ,&nbsp;Luis Cardoso ,&nbsp;Claus-Peter Richter ,&nbsp;Alessandra Carriero","doi":"10.1016/j.bone.2025.117764","DOIUrl":"10.1016/j.bone.2025.117764","url":null,"abstract":"<div><div>Hearing loss is common in people with osteogenesis imperfecta (OI or <em>brittle bone disease</em>). Bisphosphonates are widely used to treat long bone fragility in children with OI. However, its impact on the bone quality of the middle ear ossicles and hearing remains unknown. This study determines whether bisphosphonates treatment itself may contribute to hearing loss in OI by evaluating its effects in the <em>oim/oim</em> mouse model of severe OI having normal auditory function. Specifically, this study reports the effects of alendronate (ALN), a nitrogen-containing bisphosphonate, on ossicle morphology, porosity, and elemental composition in 14-week-old <em>oim/oim</em> mice treated weekly, starting at 2 weeks of age. The ossicles were examined using synchrotron microtomography and X-ray fluorescence microscopy (XFM). Hearing was assessed longitudinally until 26 weeks of age by determining auditory brainstem response (ABR) thresholds in another group of mice also treated weekly starting at 2 weeks of age. ALN treatment further reduces in size the already small <em>oim/oim</em> ossicles, specifically in female mice. Porosity, bone composition, and hearing function, however, were generally not affected by the ALN treatment. Furthermore, ALN does not prevent joint fusions, excessive bone formations, or enlarged joint spaces in WT or <em>oim/oim</em> experimental groups. One ALN-treated <em>oim/oim</em> mouse with a bone formation in the interior of the footplate, and one ALN-treated WT mouse with a fixed footplate had frequency-specific hearing loss. Since footplate abnormalities are not observed in PBS-treated mice in this study, it remains unclear whether ALN fails to prevent these changes or contributes to their development. Future studies should investigate the mechanisms of ossicular abnormalities and bisphosphonates modulatory role in the ossicles.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"204 ","pages":"Article 117764"},"PeriodicalIF":3.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145795469","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":"Region-specific variation in trapeziometacarpal joint bone microarchitecture in females with osteoarthritis assessed using HR-pQCT","authors":"Michael T. Kuczynski ,&nbsp;Charley Hasselaar ,&nbsp;Gurpreet Dhaliwal ,&nbsp;Christina Hiscox ,&nbsp;Neil J. White ,&nbsp;Danielle E. Whittier ,&nbsp;Sarah L. Manske","doi":"10.1016/j.bone.2025.117759","DOIUrl":"10.1016/j.bone.2025.117759","url":null,"abstract":"<div><div>The trapeziometacarpal (TMC) joint is commonly affected by osteoarthritis (OA), and its unique morphology creates localized loading patterns that cause regional bone adaption. Radiographic OA is more prevalent than symptomatic OA, highlighting the disconnect between structural features and clinical disease. <em>Ex vivo</em> studies have demonstrated regional changes in trapezial bone microarchitecture but are limited to cadaveric specimen with advanced disease. <em>In vivo</em> studies are needed to characterize regional bone microarchitecture in symptomatic TMC OA. We investigated regional bone microarchitecture in females with TMC OA using high-resolution peripheral quantitative computed tomography (HR-pQCT), and whether these changes differed from those associated with ageing. HR-pQCT scans of the TMC joint were acquired from 13 females with TMC OA, 12 controls matched groupwise by age and sex, and 15 sex-matched young controls. Total bone mineral density, bone volume fraction (Tt.BV/TV), thickness, and separation were quantified by quadrant in the first metacarpal and trapezium. A mixed ANOVA assessed group, quadrant, and group-by-quadrant effects. Significant interaction effects were observed for all parameters in the trapezium and separation in the first metacarpal (<em>p</em> &lt; 0.001). In OA, trapezial separation was higher, and Tt.BV/TV was lower in the ulnar-volar quadrant, while separation was lower in the radial-volar quadrant compared to young controls (<em>p</em> &lt; 0.05). In the first metacarpal, radial-volar separation was lower in OA than young controls (p &lt; 0.05). These results suggest that OA may disrupt the normal variation in first metacarpal and trapezial bone microarchitecture, highlighting the utility of HR-pQCT in early detection of structural bone changes in hand OA.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"204 ","pages":"Article 117759"},"PeriodicalIF":3.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145734244","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":"Pro-osteogenic effects of green Rooibos (Aspalathus linearis) against different dietary backgrounds in male Wistar rats","authors":"J. Khan ,&nbsp;H. Sadie-Van Gijsen ,&nbsp;L.M. Kotzé-Hörstmann ,&nbsp;S.H. Kotze ,&nbsp;S.L. Windvogel ,&nbsp;T.N. Brink ,&nbsp;J.I. Layman-Lemphane","doi":"10.1016/j.bone.2025.117743","DOIUrl":"10.1016/j.bone.2025.117743","url":null,"abstract":"<div><div>Previous in vitro studies have demonstrated direct effects of Rooibos (<em>Aspalathus linearis</em>) on bone cell populations, notably osteoblasts and osteoclasts, but in vivo evidence of Rooibos effects on bone remain scant. Here, we compared the effects of a green (minimally oxidized) Rooibos extract (GRT) on the femora of male Wistar rats, against the background of a medium-fat/high-sugar (MF/HS) and a high-fat/high-fructose (HF/Fr) diet. Male Wistar rats were maintained for 17 weeks on one of three diets: control (CON), MF/HS (OB1) or HF/Fr (OB2) (<em>n</em> = 24 each). From weeks 11–17, <em>n</em> = 12 animals in each group received oral GRT supplementation (60 mg/kg body weight daily). Femoral bone mineral content and density (BMC, BMD) were analysed by densitometry; cortical and cancellous bone microarchitecture was assessed using micro-computed tomography (μCT); and osteoblast (N.Ob), osteoclast (N.Oc), adipocyte (N.Ad) and chondrocyte numbers (N.Ch) were quantified histomorphometrically. GRT supplementation did not affect femur weight, BMC or BMD, but improved trabecular measurements were observed in the CON-GRT group, compared to all other groups. GRT increased N.Ob/mm² and decreased N.Oc/mm² in the CON and OB2 dietary groups. Notably, GRT reversed the OB2 diet-associated increase in N.Oc/mm² in both cortical and cancellous bone. Although GRT had no effect on serum malondialdehyde (MDA) levels as a measure of systemic oxidative stress status, serum MDA levels were nevertheless positively correlated with cortical and cancellous N.Oc/mm² and negatively correlated with cortical N.Ob/mm². Overall, GRT supplementation had pro-osteogenic and anti-osteoclastogenic effects in vivo, indicating that green Rooibos should be further explored as a bone-supporting nutraceutical.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"204 ","pages":"Article 117743"},"PeriodicalIF":3.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145679520","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":"Akt2 regulates autophagy and osteogenesis in diabetic osteoporosis via PI3K/AKT/mTOR signaling axis","authors":"Qiaonan Ye ,&nbsp;Ting Fu ,&nbsp;Peixuan Li ,&nbsp;Xuemei Long ,&nbsp;Zhiyuan Zhang ,&nbsp;Luwen Ye ,&nbsp;Yanqiu Zhou ,&nbsp;Shuanglin Peng ,&nbsp;Qianke Tao ,&nbsp;Jingang Xiao","doi":"10.1016/j.bone.2025.117770","DOIUrl":"10.1016/j.bone.2025.117770","url":null,"abstract":"<div><div>Adipose-derived stem cells (ASCs) are crucial seed cells for bone defect repair. In diabetic osteoporosis (DOP), however, their osteogenic potential is impaired. This study found that ASCs from a pre-clinical DOP model, established in C57BL/6 J mice using a high-fat/high-sucrose diet combined with streptozotocin-induced insulin deficiency, exhibited suppressed osteogenic differentiation and impaired autophagy flux. This was accompanied by hyperactivation of the PI3K/AKT/mTOR signaling, particularly elevated AKT2 phosphorylation. Transcriptomic analysis confirmed enrichment of related pathways. Mechanistically, <em>Akt2</em> overexpression suppressed osteogenesis and autophagy, while its knockdown restored both. Crucially, implanting sh<em>Akt2</em>-treated DOP-ASCs into calvarial defects of DOP mice enhanced bone regeneration, improving bone volume, trabecular number, and collagen deposition. These findings identify <em>Akt2</em> as a key regulator of ASC dysfunction in DOP and demonstrate that its targeted inhibition rescues osteogenic potential, offering a promising therapeutic strategy for diabetic osteoporotic bone repair.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"204 ","pages":"Article 117770"},"PeriodicalIF":3.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145837281","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":"Association between advanced glycation end products and bone mineral density in Mexican population","authors":"Diana I. Aparicio-Bautista ,&nbsp;Jorge Salmerón ,&nbsp;Rogelio F. Jiménez-Ortega ,&nbsp;Tania V. López-Pérez ,&nbsp;Adriana Becerra-Cervera ,&nbsp;Rafael Velázquez-Cruz ,&nbsp;Berenice Rivera-Paredez","doi":"10.1016/j.bone.2025.117763","DOIUrl":"10.1016/j.bone.2025.117763","url":null,"abstract":"<div><h3>Background</h3><div>Evidence shows that advanced glycation end products (AGEs) play a key role in skeletal deterioration by impacting bone quality and strength. However, there is limited long-term research on their association with bone mineral density (BMD), especially among different sexes and age groups.</div></div><div><h3>Objective</h3><div>To evaluate the longitudinal association between serum AGEs and BMD in adults, stratified by sex and age groups (&lt;45 years and ≥45 years).</div></div><div><h3>Methods</h3><div>We conducted a longitudinal analysis using data from 1138 adults enrolled in the Health Workers Cohort Study, followed over a six-year period (2004–2010). BMD (g/cm²) was measured at various skeletal sites using dual-energy X-ray absorptiometry. Generalized estimating equations (GEE) and fixed-effects models were employed, stratified by sex and age group, and adjusted for potential confounders.</div></div><div><h3>Results</h3><div>In GEE models, a 100 μU/mL increase in AGEs was significantly associated with lower BMD at the hip, femoral neck, and lumbar spine in women aged ≥45 years (β = −0.003, β = −0.004, β = −0.011, respectively). Among men ≥45 years, higher AGEs were also associated with lower BMD at the hip and femoral neck (β = −0.004 and β = −0.006, respectively). In women &lt;45 years, AGEs were inversely associated with hip and femoral neck BMD (β = −0.003 for both). Fixed-effects models yielded consistent results, particularly among women ≥45 years. No significant associations were observed in men &lt;45 years.</div></div><div><h3>Conclusions</h3><div>Elevated serum AGEs levels are associated with lower BMD over time, particularly among women. These findings suggest a potential role of AGEs in bone deterioration and their relevance in clinical risk assessment.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"204 ","pages":"Article 117763"},"PeriodicalIF":3.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145784027","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":"Craniofacial and whole-skeleton fracture patterns in osteogenesis imperfecta: Findings from a nationwide U.S. insurance claims database","authors":"Hsiao H. Sung ,&nbsp;Daniel G. Whitney ,&nbsp;Kenneth M. Kozloff ,&nbsp;Michelle S. Caird","doi":"10.1016/j.bone.2025.117762","DOIUrl":"10.1016/j.bone.2025.117762","url":null,"abstract":"<div><h3>Background</h3><div>Osteogenesis imperfecta (OI) is an inherited connective tissue disease characterized by lifelong skeletal fragility and recurrent fractures. While most prior research has focused on long bone fractures in selected clinical cohorts, population-based estimates of craniofacial and site-specific fracture risk in OI remain largely limited. This study used insurance claims data to quantify the period prevalence, anatomical distribution, and predictors of fractures in individuals with versus without OI.</div></div><div><h3>Methods</h3><div>A retrospective cohort study was conducted using the IBM® MarketScan® Multi-State Medicaid (2016–2022, all ages) and Commercial Databases (2016–2022, &lt; 65 years old). Diagnosis of OI and all fractures were identified using ICD and CPT codes recorded during healthcare encounters. The first full year of enrollment was used to determine 1-year period prevalence and counts of fractures overall and by site, stratified by age (&lt;5, 6–9, 10–13, 14–18, 19–25, ten-year intervals to &gt;55). Differences between cohorts were estimated using relative risk (RR). Associations with demographic and clinical factors were assessed via logistic regression. Proxy measures of OI severity and medical device use were applied, as clinical classification and exposure to treatments could not be directly adjudicated.</div></div><div><h3>Results</h3><div>Among 4294 individuals with OI and approximately 54.8 million controls, the overall fracture prevalence was 33.9 % in the OI cohort versus 2.5 % in controls (RR 13.6), with elevated rates observed at all anatomical sites. Jaw (craniofacial) fractures were nearly seven times more frequent in OI (0.40 % vs. 0.06 %; RR 6.7), while femur fractures showed the greatest disparity (RR 119.4). Age-specific analysis revealed the highest fracture risk for individuals with OI in early childhood, particularly at craniofacial and axial sites, with risk increasing further in those with greater proxy-measured disease severity. Female was associated with lower odds of fracture compared to males, and Medicaid coverage correlated with increased risk at select skeletal sites. Limitations include inability to distinguish fracture etiology (spontaneous, traumatic, or iatrogenic), unmeasured exposure to treatments, inability to apply clinical OI classifications, and exclusion of uninsured individuals.</div></div><div><h3>Conclusions</h3><div>Individuals with OI face a markedly greater and distinctive burden of fractures, including craniofacial involvement, than the general population. This work provides the first large-scale, population-based estimates of craniofacial fracture burden in OI, highlighting distinct age- and site-specific risk patterns. These findings reinforce the importance of ongoing, site-specific monitoring and integrated multidisciplinary care for individuals with OI, supporting clinicians in anticipatory guidance and tailored prevention strategies.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"204 ","pages":"Article 117762"},"PeriodicalIF":3.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145776810","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":"Expression of proteins secreted by osteocytes in bone biopsies of patients with chronic kidney disease and iron overload, before and after treatment with deferoxamine","authors":"Hanna Karla Andrade Guapyassu Machado ,&nbsp;Luciene Machado dos Reis ,&nbsp;Lucas Acatauassu Nunes ,&nbsp;Ivone B. Oliveira ,&nbsp;Cleonice Silva ,&nbsp;Wagner V. Dominguez ,&nbsp;Rosilene M. Elias ,&nbsp;Rosa M. Moysés ,&nbsp;Melani Custódio ,&nbsp;Vanda Jorgetti","doi":"10.1016/j.bone.2025.117754","DOIUrl":"10.1016/j.bone.2025.117754","url":null,"abstract":"<div><div>Introduction: Individuals with CKD can develop anemia, as well as mineral and bone disorder. Anemia is treated with recombinant erythropoietin and iron supplementation, which can result iron overload in various organs. Little is known about the effects of iron overload and its treatment on bone remodeling and osteocyte expression of relevant proteins. The objective of this study was to evaluate the effects that iron overload and treatment with the iron chelator deferoxamine have on parameters of iron metabolism in bone tissue and on osteocyte protein expression. Methods: This was an observational study of individuals with CKD and iron overload who underwent bone biopsy and were treated with deferoxamine. Biochemical analysis, histomorphometry, and immunohistochemistry were performed. The results were compared with those obtained for controls. Results: Deferoxamine treatment reduced all parameters of iron metabolism decreased calcium, increased alkaline phosphatase, and decreased (intact and c-terminal) fibroblast growth factor 23 levels. After treatment, trabecular separation increased, and osteoblast surface decreased. DFO treatment increased the expression of DMP-1, decreased the expression of DKK-1, PHEX and the RAGE proteins involved in bone remodeling and oxidative stress. Comparison of the expression of osteocyte proteins before and after DFO treatment with their expression in normal bone tissue, there was also increased expression of proteins that act in the formation of dendrites and cytoskeleton, such as E11 and CD44. Conclusion: In patients with CKD and iron overload, deferoxamine treatment modulates bone remodeling and expression of osteocyte proteins, which also play a role in the process.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"204 ","pages":"Article 117754"},"PeriodicalIF":3.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145696383","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":"Primary trabecular bone formation in vitro by the OmGFP66 osteogenic cell line: Multiscale symmetry breaking and characterization in 3D","authors":"Benazir Khurshid ,&nbsp;Aisha Mousa ,&nbsp;Sarah L. Dallas ,&nbsp;Joseph Deering ,&nbsp;Natalie Reznikov ,&nbsp;Marc D. McKee","doi":"10.1016/j.bone.2025.117767","DOIUrl":"10.1016/j.bone.2025.117767","url":null,"abstract":"<div><div>Osteocytes are abundant bone cells that serve as central regulators of skeletal homeostasis. Within mineralized bone tissue, osteocytes and their cell processes/dendrites maintain cell connectivity through a lacunocanalicular network morphologically positioned for executing myriad cell signaling pathways, including those related to mechanosensation, mineral ion homeostasis, and extracellular matrix mineralization. Given the complexity of osteocyte morphological transitions within mineralized bone, there are few robust <em>in vitro</em> models that reproduce the mineralized bone microenvironment. A recently developed mouse calvarial osteocyte cell line, OmGFP66, overcomes many of these limitations. Here we provide a comprehensive 3D multiscale characterization of mineralized, primary bone-like trabeculae formed by OmGFP66 cells <em>in vitro</em>, with a comparison to mouse calvariae. Submicron X-ray microcomputed tomography (μCT) was used to image and reveal quantitative features of thousands of discrete, variably shaped trabeculae formed by OmGFP66 cells with osteocyte lacunae having features quantitatively similar to those of neonatal mouse calvarial primary bone. Moreover, FIB-SEM and TEM analyses revealed the 3D ultrastructure of an extended lacunocanalicular network formed by the OmGFP66 cells within mineralized extracellular matrix and extending through an osteoid layer to osteoblasts at the surface, comparable to bone <em>in vivo</em>. At the nanoscale-to-microscale, again like bone, OmGFP66 trabeculae exhibit a 3D crossfibrillar mineral tessellation pattern. We also fit OmGFP66 trabecular morphology patterning and mineralization to the Gray-Scott model of oscillating reaction-diffusion patterns to describe symmetry breaking that initiates and facilitates mineralization through the combined dynamics of diffusing mineral ions and inhibitors. Together, these findings establish OmGFP66 cell cultures as a powerful <em>in vitro</em> bone model for studying osteocyte differentiation, matrix mineralization, and pattern formation.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"204 ","pages":"Article 117767"},"PeriodicalIF":3.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145822377","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}