Bone Reports最新文献

Identifying the best reference gene for RT-qPCR analyses of the three-dimensional osteogenic differentiation of human induced pluripotent stem cells 为人类诱导多能干细胞三维成骨分化的 RT-qPCR 分析确定最佳参考基因

IF 2.1 Q3 ENDOCRINOLOGY & METABOLISM

Bone Reports

Pub Date : 2024-11-17 DOI: 10.1016/j.bonr.2024.101816

Masakazu Okamoto , Yusuke Inagaki , Kensuke Okamura , Yoshinobu Uchihara , Kenichiro Saito , Akihito Kawai , Munehiro Ogawa , Akira Kido , Eiichiro Mori , Yasuhito Tanaka

Reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) is an essential tool for gene expression analysis; choosing appropriate reference genes for normalization is crucial to ensure data reliability. However, most studies on osteogenic differentiation have had limited success in identifying optimal reference genes. To the best of our knowledge, no optimal reference genes in three-dimensional (3D) osteogenic differentiation culture experiments using human induced pluripotent stem cells (hiPSCs) have been identified. In this study, we aimed to identify stable reference genes that could be used for normalization in gene expression analyses during the 3D osteogenic differentiation of hiPSCs using an atelocollagen sponge as a scaffold. Four algorithms—ΔCt, BestKeeper, NormFinder, and geNorm—were used to evaluate the stability of 14 candidate reference genes. Genes encoding TATA box-binding protein, hypoxanthine phosphoribosyltransferase 1, and 14–3-3 protein zeta polypeptide were identified as the most stable reference genes. In comparison, conventionally used reference genes (beta-2 microglobulin and beta-actin genes) ranked among those with low stability. We also demonstrated the successful 3D osteogenic differentiation of hiPSCs on atelocollagen sponge. Our findings provide valuable insights for reference gene selection and bone tissue regeneration from hiPSCs, which could improve the treatment prospects for bone defects and other similar conditions in regenerative medicine.

反转录实时定量聚合酶链反应（RT-qPCR）是基因表达分析的重要工具；选择适当的参考基因进行归一化是确保数据可靠性的关键。然而，大多数成骨分化研究在确定最佳参考基因方面的成功率有限。据我们所知，在使用人类诱导多能干细胞（hiPSCs）进行的三维（3D）成骨分化培养实验中，尚未发现最佳参考基因。在这项研究中，我们的目的是找出稳定的参考基因，用于以阿特劳胶原海绵为支架的 hiPSCs 三维成骨分化过程中基因表达分析的归一化。四种算法--ΔCt、BestKeeper、NormFinder 和 geNorm--用于评估 14 个候选参考基因的稳定性。结果发现，编码 TATA 盒结合蛋白、次黄嘌呤磷酸核糖转移酶 1 和 14-3-3 蛋白 zeta 多肽的基因是最稳定的参考基因。相比之下，传统的参考基因（β-2微球蛋白和β-肌动蛋白基因）稳定性较低。我们还证明了 hiPSCs 在阿特劳胶原海绵上成功进行了三维成骨分化。我们的研究结果为参考基因的选择和 hiPSCs 的骨组织再生提供了宝贵的见解，可改善再生医学中骨缺损和其他类似病症的治疗前景。

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引用次数: 0

Naringin promotes osteogenic potential in bone marrow-derived mesenchymal stem cells via mediation of miR-26a/Ski axis 柚皮素通过调控 miR-26a/Ski 轴促进骨髓间充质干细胞的成骨潜能

IF 2.1 Q3 ENDOCRINOLOGY & METABOLISM

Bone Reports

Pub Date : 2024-11-13 DOI: 10.1016/j.bonr.2024.101815

Jiawei Zou, Longze Zhou, Guoqiang Liu, Ying Zhang, Lingguo Zeng

Background

Osteonecrosis of the femoral head (ONFH) is a common orthopedic disease, which seriously affects the quality of life of patients. Naringin has protective effect on ONFH. In present study, we aimed to investigate the mechanism of Naringin regulating miR-26a in ONFH.

Methods

Two sequencing datasets (GSE89587 for micro-RNA, GSE123568 for mRNA) related to ONFH were obtained from the GEO database for bioinformatics analysis. Bone marrow-derived mesenchymal stem cells (BMSCs) were treated with adipogenic medium (AM) or osteogenic medium (OM), and then treated with 10 μM, 100 μM or 1000 μM Naringin. Gene and protein levels were detected by RT-qPCR and Western blotting. ALP activity and alizarin red staining (ARS) were applied to investigate the osteogenic differentiation of BMSCs. Oil red O staining was performed to test adipogenic differentiation. The content of triglycerides (TG) in BMSCs was detected by TG detection kit. Double luciferase reporter gene measured the interaction between miR-26a and Ski.

Results

Bioinfomatic analyses indicated a significant downregulation of miR-26a and a significant upregulation of Ski in the peripheral blood of patients with ONFH. Naringin significantly promoted the osteogenic differentiation, and increased the ALP activity and ARS. Meanwhile, it decreased the adipogenic differentiation and inhibited TG levels. In addition, miR-26a was downregulated and Ski was increased in AM-treated BMSCs, while miR-26a was upregulated and Ski was decreased in OM-treated BMSCs. Furthermore, miR-26a promoted the osteogenic differentiation and suppressed the adipogenic differentiation in BMSCs. Moreover, Naringin enhanced osteogenic potential in BMSCs was reversed by knockdown of miR-26a or overexpression of Ski.

Conclusion

Naringin could promote osteogenic differentiation of BMSCs via mediation of miR-26a/Ski axis. Thereby, Naringin might be a new agent for ONFH treatment.

背景股骨头骨坏死（ONFH）是一种常见的骨科疾病，严重影响患者的生活质量。柚皮素对股骨头坏死有保护作用。本研究旨在探讨柚皮素调控miR-26a在股骨头坏死中的作用机制。方法从GEO数据库获取两个与股骨头坏死相关的测序数据集（微RNA数据集GSE89587，mRNA数据集GSE123568）进行生物信息学分析。骨髓间充质干细胞（BMSCs）经成脂培养基（AM）或成骨培养基（OM）处理，然后用 10 μM、100 μM 或 1000 μM 柚皮甙处理。通过 RT-qPCR 和 Western 印迹检测基因和蛋白质水平。ALP 活性和茜素红染色（ARS）用于研究 BMSCs 的成骨分化。油红 O 染色用于检测成脂分化。用甘油三酯检测试剂盒检测 BMSCs 中甘油三酯（TG）的含量。结果生物信息学分析表明，在ONFH患者的外周血中，miR-26a显著下调，Ski显著上调。柚皮苷能明显促进成骨分化，提高 ALP 活性和 ARS。同时，柚皮苷能减少脂肪分化并抑制 TG 水平。此外，在AM处理的BMSCs中，miR-26a下调，Ski增加；而在OM处理的BMSCs中，miR-26a上调，Ski减少。此外，miR-26a 促进了 BMSCs 的成骨分化，抑制了成脂分化。结论柚皮素可通过调控 miR-26a/Ski 轴促进 BMSCs 的成骨分化。因此，柚皮苷可能是一种治疗ONFH的新药物。

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引用次数: 0

Improvements with burosumab treatment in an early access programme for adults with X-linked hypophosphataemia: A case series of three patients X连锁低磷血症成人患者早期接受布芦单抗治疗后病情有所改善：三名患者的病例系列

IF 2.1 Q3 ENDOCRINOLOGY & METABOLISM

Bone Reports

Pub Date : 2024-11-12 DOI: 10.1016/j.bonr.2024.101814

Julia Day , Chandrin Jayatilleke , Matthew Roy

X-linked hypophosphataemia (XLH) is a life-long phosphate-wasting disorder that causes skeletal deformities, pain, stiffness, and fatigue and impairs quality of life. Burosumab was approved for use in adults in 2020. We describe three adults with persistent XLH symptoms who received burosumab treatment in a real-world setting. Patients report improvements in pain, mobility, physical function, energy, fatigue, and mental wellbeing through patient-reported outcome measures, enriched with further detail from written testimonials.

X连锁低磷血症（XLH）是一种终身性磷酸盐消耗性疾病，会导致骨骼畸形、疼痛、僵硬和疲劳，并影响生活质量。布罗苏单抗于 2020 年获准用于成人。我们描述了在现实世界中接受布罗苏单抗治疗的三名具有持续XLH症状的成人患者的情况。患者通过患者报告的结果指标报告了疼痛、活动能力、身体功能、精力、疲劳和精神健康的改善情况，并从书面证词中获得了更多细节。

引用次数: 0

Association of daily physical activity and bone microarchitecture in young adults with type 1 diabetes — A pilot exploratory study 1 型糖尿病年轻成人的日常体育锻炼与骨骼微结构的关系--一项探索性试点研究

IF 2.1 Q3 ENDOCRINOLOGY & METABOLISM

Bone Reports

Pub Date : 2024-11-09 DOI: 10.1016/j.bonr.2024.101813

Sarah L. West , Michelle Furman , Rahim Moineddin , Etienne Sochett

Purpose

Physical activity (PA) is an important determinant of skeletal health. In young adults with type 1 diabetes (T1D) fracture risk is increased, yet few studies have examined the PA and bone health relationship. Therefore, this pilot cross-sectional study characterized PA levels and their association with bone parameters measured by high resolution peripheral quantitative computed tomography (HR-pQCT) in young adults with T1D.

Methods

HR-pQCT (Xtreme CTII) was used to measure bone outcomes at the distal tibia and radius, and accelerometery (ActiGraph GT3X) recorded daily minutes of light and moderate-vigorous physical activity (MVPA). Quadratic regression analyses were conducted with a p-value ≤ 0.05 considered significant.

Results

PA data from 19 young adults (23.1 ± 1.9 years) with T1D was analyzed. Over half (63 %) of participants completed ≥150 min of MVPA per week, however, most measured activity time per day (57 %) was spent in sedentary pursuits. Significant non-linear associations were found between the duration of MVPA and several trabecular bone parameters at the tibia.

Conclusions

In young adults with T1D, MVPA may have site specific (tibia) and compartment specific (trabecular) non-linear associations with bone. Further studies should confirm these findings, which may help inform evidence-based exercise recommendations to optimize bone health in young adults with T1D.

目的体力活动（PA）是骨骼健康的重要决定因素。1 型糖尿病（T1D）患者骨折风险增加，但很少有研究探讨 PA 与骨骼健康的关系。因此，本试验性横断面研究对 T1D 患者的 PA 水平及其与通过高分辨率外周定量计算机断层扫描（HR-pQCT）测量的骨骼参数之间的关系进行了描述。HR-pQCT（Xtreme CTII）用于测量胫骨远端和桡骨的骨骼结果，加速度计（ActiGraph GT3X）用于记录每天轻度和中度剧烈运动（MVPA）的分钟数。结果分析了 19 名患有 T1D 的年轻人（23.1 ± 1.9 岁）的运动数据。半数以上（63%）的参与者每周完成的 MVPA 时间≥150 分钟，然而，大多数测得的每日活动时间（57%）都花在了久坐不动的活动上。结论在患有 T1D 的年轻人中，MVPA 可能与骨骼有特定部位（胫骨）和特定区段（骨小梁）的非线性关系。进一步的研究应确认这些发现，这可能有助于为循证运动建议提供依据，从而优化 T1D 青壮年患者的骨骼健康。

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引用次数: 0

Zoledronate interrupts pre-osteoclast-induced angiogenesis via SDF-1/CXCR4 pathway 唑来膦酸钠通过 SDF-1/CXCR4 通路阻断破骨细胞前期诱导的血管生成

IF 2.1 Q3 ENDOCRINOLOGY & METABOLISM

Bone Reports

Pub Date : 2024-11-04 DOI: 10.1016/j.bonr.2024.101812

Mohamed Awad , Elizabeth Taylor-Diaz , Amany Tawfik , Khaled Hussein , Ahmed Elmansi , Mahmoud Elashiry , Ranya Elsayed , Linah Shahoumi , James Borke , William Hill , Fanglong Dong , Mohammed E. Elsalanty

Introduction

In this study, we tested the hypothesis that pre-osteoclast signaling is key in triggering post-traumatic angiogenesis in alveolar bone via the SDF-1/CXCR4 pathway. Interruption of osteoclast differentiation through zoledronate (Zol) disrupts the crosstalk between pre-osteoclasts and endothelial cells, hindering the initial angiogenic reaction following dental trauma. This disruption could therefore play a role in the pathogenesis of medication-related osteonecrosis of the jaw (MRONJ).

Methods

The effect of zoledronate on the expression of SDF1 was tested in pre-osteoclasts (POC) in vitro. Then, we tested the effect of pre-osteoclast conditioned medium on HUVEC cell differentiation, migration, tube-formation, and CXCR4 expression and activity in-vitro. Lastly, we quantified the effect of zoledronate treatment on post-traumatic vascular perfusion of alveolar bone, using microCT-angiography and immunohistochemistry.

Results

SDF-1 mRNA expression decreased in Zol-treated POCs (p = 0.02). Flow-Cytometry analysis showed a decrease in CXCL-12⁺ (SDF-1α) expressing POCs with Zol treatment (p = 0.0058). On the other hand, CXCR4 mRNA expression was significantly inhibited in Zol-treated HUVECs (p = 0.0063). CXCR4 protein expression and activity showed a corresponding dose-dependent downregulation HUVEC surface treated with conditioned media from POC treated with Zol (p = 0.008 and 0.03, respectively). Similar inhibition was observed of HUVEC migration (p = 0.0012), and tube formation (p < 0.0001), effects that were reversed with SDF-1. Finally, there was a significant reduction of CD31⁺ HUVECs in Alveolar bone of Zol-treated rats (p = 0.0071), confirmed by significantly lower percentage of blood vessel volume (p = 0.026), and marginally lower vessel number (p = 0.062) in the alveolar bone.

Conclusion

Pre-osteoclasts play a crucial role in the initial angiogenic response in alveolar bone following dental extraction. Disruption of this process may be a predisposing factor to osteonecrosis.

引言在这项研究中，我们检验了一种假设，即前破骨细胞信号传导是通过SDF-1/CXCR4通路触发牙槽骨创伤后血管生成的关键。通过唑来膦酸盐（Zoledronate，Zol）中断破骨细胞分化会破坏前破骨细胞和内皮细胞之间的串联，从而阻碍牙外伤后的初始血管生成反应。方法在体外测试唑来膦酸钠对破骨细胞前期（POC）中 SDF1 表达的影响。然后，我们在体外测试了前破骨细胞条件培养基对 HUVEC 细胞分化、迁移、管形成以及 CXCR4 表达和活性的影响。最后，我们使用显微 CT 血管造影术和免疫组织化学方法量化了唑来膦酸钠治疗对创伤后牙槽骨血管灌注的影响。流式细胞术分析表明，经 Zol 处理后，表达 CXCL-12+ （SDF-1α）的 POCs 减少（p = 0.0058）。另一方面，Zol 处理的 HUVECs 中 CXCR4 mRNA 的表达受到显著抑制（p = 0.0063）。用 Zol 处理的 POC 条件培养基处理的 HUVEC 表面，CXCR4 蛋白表达和活性也出现了相应剂量依赖性的下调（p = 0.008 和 0.03，分别为 0.008 和 0.03）。对 HUVEC 迁移（p = 0.0012）和管形成（p < 0.0001）也观察到类似的抑制作用，这些作用在 SDF-1 的作用下被逆转。最后，经 Zol 处理的大鼠牙槽骨中 CD31+ HUVECs 明显减少（p = 0.0071），牙槽骨中血管体积百分比明显降低（p = 0.026），血管数量也略有减少（p = 0.062）。这一过程的破坏可能是骨坏死的诱发因素。

{"title":"Zoledronate interrupts pre-osteoclast-induced angiogenesis via SDF-1/CXCR4 pathway","authors":"Mohamed Awad , Elizabeth Taylor-Diaz , Amany Tawfik , Khaled Hussein , Ahmed Elmansi , Mahmoud Elashiry , Ranya Elsayed , Linah Shahoumi , James Borke , William Hill , Fanglong Dong , Mohammed E. Elsalanty","doi":"10.1016/j.bonr.2024.101812","DOIUrl":"10.1016/j.bonr.2024.101812","url":null,"abstract":"<div><h3>Introduction</h3><div>In this study, we tested the hypothesis that pre-osteoclast signaling is key in triggering post-traumatic angiogenesis in alveolar bone via the SDF-1/CXCR4 pathway. Interruption of osteoclast differentiation through zoledronate (Zol) disrupts the crosstalk between pre-osteoclasts and endothelial cells, hindering the initial angiogenic reaction following dental trauma. This disruption could therefore play a role in the pathogenesis of medication-related osteonecrosis of the jaw (MRONJ).</div></div><div><h3>Methods</h3><div>The effect of zoledronate on the expression of SDF1 was tested in pre-osteoclasts (POC) in vitro. Then, we tested the effect of pre-osteoclast conditioned medium on HUVEC cell differentiation, migration, tube-formation, and CXCR4 expression and activity in-vitro. Lastly, we quantified the effect of zoledronate treatment on post-traumatic vascular perfusion of alveolar bone, using microCT-angiography and immunohistochemistry.</div></div><div><h3>Results</h3><div>SDF-1 mRNA expression decreased in Zol-treated POCs (<em>p</em> = 0.02). Flow-Cytometry analysis showed a decrease in CXCL-12<sup>+</sup> (SDF-1α) expressing POCs with Zol treatment (<em>p</em> = 0.0058). On the other hand, CXCR4 mRNA expression was significantly inhibited in Zol-treated HUVECs (<em>p</em> = 0.0063). CXCR4 protein expression and activity showed a corresponding dose-dependent downregulation HUVEC surface treated with conditioned media from POC treated with Zol (<em>p</em> = 0.008 and 0.03, respectively). Similar inhibition was observed of HUVEC migration (<em>p</em> = 0.0012), and tube formation (<em>p</em> < 0.0001), effects that were reversed with SDF-1. Finally, there was a significant reduction of CD31<sup>+</sup> HUVECs in Alveolar bone of Zol-treated rats (<em>p</em> = 0.0071), confirmed by significantly lower percentage of blood vessel volume (<em>p</em> = 0.026), and marginally lower vessel number (<em>p</em> = 0.062) in the alveolar bone.</div></div><div><h3>Conclusion</h3><div>Pre-osteoclasts play a crucial role in the initial angiogenic response in alveolar bone following dental extraction. Disruption of this process may be a predisposing factor to osteonecrosis.</div></div>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"23 ","pages":"Article 101812"},"PeriodicalIF":2.1,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142658286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Treatment with bariatric surgery in patients with osteogenesis imperfecta and severe obesity 用减肥手术治疗成骨不全症和重度肥胖症患者

IF 2.1 Q3 ENDOCRINOLOGY & METABOLISM

Bone Reports

Pub Date : 2024-10-21 DOI: 10.1016/j.bonr.2024.101811

Jannie Dahl Hald , Asta-Marie Welander Hald , Torben Harsløf , Bente Langdahl , Jens Meldgaard Bruun

引用次数: 0

Voluntary exercise in mice triggers an anti-osteogenic and pro-tenogenic response in the ankle joint without affecting long bones 小鼠的自主运动会引发踝关节的抗骨质生成和促韧反应，但不会影响长骨

IF 2.1 Q3 ENDOCRINOLOGY & METABOLISM

Bone Reports

Pub Date : 2024-10-15 DOI: 10.1016/j.bonr.2024.101810

Anne Briolay , François Duboeuf , Séverine Delplace , Leyre Brizuela , Olivier Peyruchaud , David Magne , Carole Bougault

Biomechanical stimulation is proposed to occupy a central place in joint homeostasis, but the precise contribution of exercise remains elusive. We aimed to characterize in vivo the impact of mechanical stimulation on the cell-controlled regulation of ossification within the ankles of healthy mice undergoing mild physical activity. DBA/1 male mice were subjected to voluntary running exercise for two weeks, and compared to mice housed in standard conditions (n = 20 per group). Free access to activity wheels resulted in a running exercise of 5.5 ± 0.8 km/day at 14.5 ± 0.5 m/min. Serum levels of alkaline phosphatase, IL-6, IL-8/Kc, IL-17a, and TNF-α were measured. No change in systemic inflammation was detected. The bone architecture of the femur and the calcaneus was unchanged, as revealed by μCT and histology of the enthesis of the Achilles tendon. mRNAs were extracted from femurs, tibias, and ankle joints before RT-qPCR analysis. The expression of the mechanosensitive genes Sclerostin (Sost) and Periostin (Postn) was not impacted by the exercise in long bones. Oppositely, Sost and Postn levels were modulated by exercise in joints, and osteogenic markers (Col10a1, Runx2, Osx, and Dmp1) were downregulated in the exercise group. In addition, the tenogenic markers Scx, Mkx, and Tnmd were upregulated by exercise. Thus, voluntary exercise affected the phenotype of joint cells without impacting long bones. As gene expression of Bmp2, Bmp4, and Id1 was also reduced in these cells, an off-regulation of BMP signaling could be partly responsible for their mechanosensitive response. Running exercise seemed to preserve the tendon from its progressive ossification, as seen in numerous enthesopathies. This study paves the way to future experiments for investigating the effects of mechanical stimulation in various mouse models.

生物机械刺激被认为在关节稳态中占据着核心地位，但运动的确切贡献仍然难以捉摸。我们的目的是在体内描述机械刺激对健康小鼠在轻微运动时脚踝骨化的细胞控制调节的影响。我们对 DBA/1 雄性小鼠进行了为期两周的自愿跑步锻炼，并与标准条件下饲养的小鼠进行了比较（每组 20 只）。小鼠每天以 14.5 ± 0.5 米/分钟的速度自由使用活动轮，跑动距离为 5.5 ± 0.8 公里。测量了血清中碱性磷酸酶、IL-6、IL-8/Kc、IL-17a 和 TNF-α 的水平。未检测到全身炎症的变化。μCT和跟腱内膜组织学检查显示，股骨和小腿骨的骨结构没有变化。长骨中机械敏感基因 Sclerostin（Sost）和 Periostin（Postn）的表达不受运动影响。相反，关节中的 Sost 和 Postn 水平受运动影响，而成骨标志物（Col10a1、Runx2、Osx 和 Dmp1）在运动组中下调。此外，运动还上调了韧带生成标志物 Scx、Mkx 和 Tnmd。因此，自主运动会影响关节细胞的表型，但不会影响长骨。由于这些细胞中Bmp2、Bmp4和Id1的基因表达也减少了，BMP信号的非调控可能是造成其机械敏感性反应的部分原因。跑步运动似乎能保护肌腱，使其免于逐渐骨化，这在许多骨关节病中都能看到。这项研究为今后在各种小鼠模型中研究机械刺激的影响铺平了道路。

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引用次数: 0

Delineating the nexus between gut-intratumoral microbiome and osteo-immune system in bone metastases 阐明骨转移瘤中肠道-瘤内微生物群与骨免疫系统之间的联系

IF 2.1 Q3 ENDOCRINOLOGY & METABOLISM

Bone Reports

Pub Date : 2024-10-10 DOI: 10.1016/j.bonr.2024.101809

Shreya Kapoor, Muskan Gupta , Leena Sapra , Taranjeet Kaur, Rupesh K. Srivastava

Emerging insights in osteoimmunology have enabled researchers to explore in depth the role of immune modulation in regulating bone health. Bone is one of the common sites of metastasis notably in case of breast cancer, prostate cancer and several other cancer types. High calcium ion concentration and presence of several factors within the mineralized bone matrix including TGF-β, BMP etc., aid in tumor growth and proliferation. Accumulating evidence has substantiated the role of the gut-microbiota (GM) in tumorigenesis, further providing a strong impetus for the growing “immune-cancer-gut microbiota” relationship. Recent advancements in research further highlight the importance of the intra-tumor microbiota in conjunction with GM in cancer metastasis. Intratumoral microbiota owing to their ability to cause genetic instability, mutations, and epigenetic modifications within the tumor microenvironment, has been recognized to affect cancer cell physiology. The host microbiota and immune system crosstalk shapes the innate and adaptive arms of the immune system, which is the key player in cancer progression. In this review, we aim to decipher the role of microorganisms mediating bone metastasis by shedding light on the immuno-onco-microbiome (IOM) axis. We discussed the feasible cancer therapeutic interventions based on the modulation of the microbiome-immune cell axis which includes prebiotics, probiotics, and postbiotics. Here, we leverage the conceptual framework based on the published articles on microbiota-based therapies to target bone metastases. Understanding this complicated nexus will provide insights into fundamental factors governing bone metastases which will subsequently help in managing this malignancy with better efficacy.

骨免疫学的新进展使研究人员能够深入探讨免疫调节在调节骨骼健康中的作用。骨骼是癌症转移的常见部位之一，尤其是乳腺癌、前列腺癌和其他几种癌症。高钙离子浓度和矿化骨基质中存在的多种因子（包括 TGF-β、BMP 等）有助于肿瘤的生长和增殖。越来越多的证据证实了肠道微生物群（GM）在肿瘤发生中的作用，这进一步有力地推动了 "免疫-癌症-肠道微生物群 "关系的发展。最近的研究进展进一步凸显了肿瘤内微生物群与肠道微生物群在癌症转移中的重要性。肿瘤内微生物群由于能够导致肿瘤微环境中的遗传不稳定性、突变和表观遗传学改变，因此已被公认为会影响癌细胞的生理学。宿主微生物群和免疫系统的相互影响塑造了免疫系统的先天性和适应性臂膀，而先天性和适应性臂膀是癌症进展过程中的关键角色。在这篇综述中，我们旨在通过揭示免疫-生态-微生物组（IOM）轴来解读微生物介导骨转移的作用。我们讨论了基于微生物组-免疫细胞轴（包括益生菌、益生菌和后益生菌）调节的可行癌症治疗干预措施。在此，我们根据已发表的有关基于微生物群的疗法的文章，利用概念框架来治疗骨转移。了解这一复杂的关系将有助于深入了解骨转移的基本因素，从而有助于以更好的疗效控制这种恶性肿瘤。

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引用次数: 0

Administration of low intensity vibration and a RANKL inhibitor, alone or in combination, reduces bone loss after spinal cord injury-induced immobilization in rats 单独或联合使用低强度振动和 RANKL 抑制剂可减少脊髓损伤引起的大鼠固定后的骨质流失

IF 2.1 Q3 ENDOCRINOLOGY & METABOLISM

Bone Reports

Pub Date : 2024-10-02 DOI: 10.1016/j.bonr.2024.101808

Yuanzhen Peng , Helen M. Bramlett , W. Dalton Dietrich , Alex Marcillo , Juliana Sanchez-Molano , Ofelia Furones-Alonso , Jay J. Cao , Jenney Huang , Andrew A. Li , Jian Q. Feng , William A. Bauman , Weiping Qin

We previously reported an ability of low-intensity vibration (LIV) to improve selected biomarkers of bone turnover and gene expression and reduce osteoclastogenesis but lacking of evident bone accrual. In this study, we demonstrate that a prolonged course of LIV that initiated at 2 weeks post-injury and continued for 8 weeks can protect against bone loss after SCI in rats. LIV stimulates bone formation and improves osteoblast differentiation potential of bone marrow stromal stem cells while inhibiting osteoclast differentiation potential of marrow hematopoietic progenitors to reduce bone resorption. We further demonstrate that the combination of LIV and RANKL antibody reduces SCI-related bone loss more than each intervention alone. Our findings that LIV is efficacious in maintaining sublesional bone mass suggests that such physical-based intervention approach would be a noninvasive, simple, inexpensive and practical intervention to treat bone loss after SCI. Because the combined administration of LIV and RANKL inhibition better preserved sublesional bone after SCI than either intervention alone, this work provides the impetus for the development of future clinical protocols based on the potential greater therapeutic efficacy of combining non-pharmacological (e.g., LIV) and pharmacological (e.g., RANKL inhibitor or other agents) approaches to treat osteoporosis after SCI or other conditions associated with severe immobilization.

我们以前曾报道过低强度振动（LIV）能够改善选定的骨转换生物标志物和基因表达，减少破骨细胞生成，但缺乏明显的骨累积。在这项研究中，我们证明了从受伤后 2 周开始并持续 8 周的长期低强度振动疗法可以防止大鼠在 SCI 后出现骨质流失。LIV 可刺激骨形成，提高骨髓基质干细胞的成骨细胞分化潜能，同时抑制骨髓造血祖细胞的破骨细胞分化潜能，从而减少骨吸收。我们进一步证明，LIV 和 RANKL 抗体的组合比单独使用两种干预措施更能减少 SCI 相关骨质流失。我们的研究结果表明，LIV 能有效维持局部骨量，这表明这种以物理为基础的干预方法是治疗 SCI 后骨质流失的一种无创、简单、廉价且实用的干预方法。由于联合施用 LIV 和 RANKL 抑制剂比单独施用其中一种干预措施能更好地保护 SCI 后的皮下骨质，因此这项研究为未来临床方案的开发提供了动力，而未来的临床方案将基于非药物疗法（如 LIV）和药物疗法（如 RANKL 抑制剂或其他药物）相结合的潜在更大疗效，以治疗 SCI 后或其他与严重固定相关的骨质疏松症。

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引用次数: 0

Utility of ultrasound imaging in monitoring fracture healing in rat femur: Comparison with other imaging modalities 超声成像在监测大鼠股骨骨折愈合中的作用：与其他成像模式的比较

IF 2.1 Q3 ENDOCRINOLOGY & METABOLISM

Bone Reports

Pub Date : 2024-09-23 DOI: 10.1016/j.bonr.2024.101807

Satoshi Inoue , Michinori Mori , Masaya Yasui , Miwako Matsuki-Fukushima , Kentaro Yoshimura , Naoko Nonaka

Objective

Fractures are common injuries and various imaging modalities are employed to diagnose and monitor bone union. However, the follow-up of fracture healing using ultrasound imaging (US) remains a topic of debate. In this study, we analyzed of fracture healing process and compared US and radiological analyses with histological analyses to clarify the characteristics and limitations of each modality.

Methods

An osteotomy model was created using the femur of Wistar rats, and US, radiological (radiography and micro-computed tomography (micro-CT)), and histological analyses were performed. Radiological assessments were conducted for the evaluation of calcified tissue. The gap between the bony callus and cartilaginous callus was measured.

Results

US effectively captured changes on the fracture surface, potentially reflecting the early healing processes. Both US and radiographic findings showed strong correlation in terms of the decrease in the bony callus gap. US was unable to distinguish cartilaginous callus from the surrounding soft tissue. During the remodeling stage, micro-CT offered a detailed assessment of the internal fracture surface, whereas US was limited to evaluating the outer bone surface and lacked accuracy in visualizing the entire fracture site. Radiography provided a general overview of the fractures. The decrease in the bony callus gap measured using US correlated with the reduction in cartilaginous callus observed histologically.

Conclusion

This study demonstrated that US could be a valuable tool for evaluating fracture healing. Combining fracture management with US and radiological examinations may provide a more accurate assessment of healing progress.

目的骨折是一种常见的损伤，人们采用各种成像模式来诊断和监测骨结合情况。然而，使用超声成像（US）对骨折愈合进行随访仍是一个争论不休的话题。在这项研究中，我们分析了骨折愈合过程，并将超声成像和放射学分析与组织学分析进行了比较，以明确每种成像方式的特点和局限性。放射学评估用于评价钙化组织。结果超声波有效捕捉了骨折表面的变化，可能反映了早期愈合过程。就骨胼胝体间隙的缩小而言，超声波和放射学检查结果显示出很强的相关性。US 无法区分软骨胼胝和周围软组织。在重塑阶段，显微 CT 可对骨折内部表面进行详细评估，而 US 只能评估骨外表面，无法准确观察整个骨折部位。X 射线照相可提供骨折的总体情况。通过 US 测量到的骨胼胝间隙的减少与组织学观察到的软骨胼胝的减少相关。将骨折处理与 US 和放射学检查相结合，可以更准确地评估愈合进展。

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