Bone Research最新文献_第3页

Bifidobacterium animalis subsp. lactis A6 ameliorates bone and muscle loss via modulating gut microbiota composition and enhancing butyrate production 动物双歧杆菌亚种。乳酸A6通过调节肠道菌群组成和提高丁酸盐产量来改善骨和肌肉损失

IF 12.7 1区医学

Bone Research Pub Date : 2025-02-25 DOI: 10.1038/s41413-024-00381-1

Ming Chen, Yi Li, Zhengyuan Zhai, Hui Wang, Yuan Lin, Feifan Chang, Siliang Ge, Xinyu Sun, Wei Wei, Duanyang Wang, Mingming Zhang, Ruijing Chen, Haikuan Yu, Taojin Feng, Xiang Huang, Dongliang Cheng, Jiang Liu, Wenxuan Di, Yanling Hao, Pengbin Yin, Peifu Tang

{"title":"Bifidobacterium animalis subsp. lactis A6 ameliorates bone and muscle loss via modulating gut microbiota composition and enhancing butyrate production","authors":"Ming Chen, Yi Li, Zhengyuan Zhai, Hui Wang, Yuan Lin, Feifan Chang, Siliang Ge, Xinyu Sun, Wei Wei, Duanyang Wang, Mingming Zhang, Ruijing Chen, Haikuan Yu, Taojin Feng, Xiang Huang, Dongliang Cheng, Jiang Liu, Wenxuan Di, Yanling Hao, Pengbin Yin, Peifu Tang","doi":"10.1038/s41413-024-00381-1","DOIUrl":"https://doi.org/10.1038/s41413-024-00381-1","url":null,"abstract":"Systematic bone and muscle loss is a complex metabolic disease, which is frequently linked to gut dysfunction, yet its etiology and treatment remain elusive. While probiotics show promise in managing diseases through microbiome modulation, their therapeutic impact on gut dysfunction-induced bone and muscle loss remains to be elucidated. Employing dextran sulfate sodium (DSS)-induced gut dysfunction model and wide-spectrum antibiotics (ABX)-treated mice model, our study revealed that gut dysfunction instigates muscle and bone loss, accompanied by microbial imbalances. Importantly, Bifidobacterium animalis subsp. lactis A6 (B. lactis A6) administration significantly ameliorated muscle and bone loss by modulating gut microbiota composition and enhancing butyrate-producing bacteria. This intervention effectively restored depleted butyrate levels in serum, muscle, and bone tissues caused by gut dysfunction. Furthermore, butyrate supplementation mitigated musculoskeletal loss by repairing the damaged intestinal barrier and enriching beneficial butyrate-producing bacteria. Importantly, butyrate inhibited the NF-κB pathway activation, and reduced the secretion of corresponding inflammatory factors in T cells. Our study highlights the critical role of dysbiosis in gut dysfunction-induced musculoskeletal loss and underscores the therapeutic potential of B. lactis A6. These discoveries offer new microbiome directions for translational and clinical research, providing promising strategies for preventing and managing musculoskeletal diseases.","PeriodicalId":9134,"journal":{"name":"Bone Research","volume":"31 1","pages":""},"PeriodicalIF":12.7,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143485687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Iron homeostasis and ferroptosis in muscle diseases and disorders: mechanisms and therapeutic prospects 肌肉疾病中的铁稳态和铁下垂：机制和治疗前景

IF 12.7 1区医学

Bone Research Pub Date : 2025-02-25 DOI: 10.1038/s41413-024-00398-6

Qin Ru, Yusheng Li, Xi Zhang, Lin Chen, Yuxiang Wu, Junxia Min, Fudi Wang

{"title":"Iron homeostasis and ferroptosis in muscle diseases and disorders: mechanisms and therapeutic prospects","authors":"Qin Ru, Yusheng Li, Xi Zhang, Lin Chen, Yuxiang Wu, Junxia Min, Fudi Wang","doi":"10.1038/s41413-024-00398-6","DOIUrl":"https://doi.org/10.1038/s41413-024-00398-6","url":null,"abstract":"The muscular system plays a critical role in the human body by governing skeletal movement, cardiovascular function, and the activities of digestive organs. Additionally, muscle tissues serve an endocrine function by secreting myogenic cytokines, thereby regulating metabolism throughout the entire body. Maintaining muscle function requires iron homeostasis. Recent studies suggest that disruptions in iron metabolism and ferroptosis, a form of iron-dependent cell death, are essential contributors to the progression of a wide range of muscle diseases and disorders, including sarcopenia, cardiomyopathy, and amyotrophic lateral sclerosis. Thus, a comprehensive overview of the mechanisms regulating iron metabolism and ferroptosis in these conditions is crucial for identifying potential therapeutic targets and developing new strategies for disease treatment and/or prevention. This review aims to summarize recent advances in understanding the molecular mechanisms underlying ferroptosis in the context of muscle injury, as well as associated muscle diseases and disorders. Moreover, we discuss potential targets within the ferroptosis pathway and possible strategies for managing muscle disorders. Finally, we shed new light on current limitations and future prospects for therapeutic interventions targeting ferroptosis.","PeriodicalId":9134,"journal":{"name":"Bone Research","volume":"27 1","pages":""},"PeriodicalIF":12.7,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143485688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Targeting AKT as a promising strategy for SOX2-positive, chemoresistant osteosarcoma 靶向 AKT 是治疗 SOX2 阳性、化疗耐药骨肉瘤的有效策略

IF 12.7 1区医学

Bone Research Pub Date : 2025-02-24 DOI: 10.1038/s41413-024-00395-9

Yujie Liu, Li Kang, Jing Luo, Minglei Yang, Da Wang, Juelan Ye, Xinghai Yang, Wei Wan, Jiemin Wong, Jianru Xiao

{"title":"Targeting AKT as a promising strategy for SOX2-positive, chemoresistant osteosarcoma","authors":"Yujie Liu, Li Kang, Jing Luo, Minglei Yang, Da Wang, Juelan Ye, Xinghai Yang, Wei Wan, Jiemin Wong, Jianru Xiao","doi":"10.1038/s41413-024-00395-9","DOIUrl":"https://doi.org/10.1038/s41413-024-00395-9","url":null,"abstract":"Osteosarcoma (OS) is the most prevalent type of primary malignant bone cancer and currently lacks effective targeted treatments. Increasing evidence indicates that SOX2 overexpression is a primary driver of OS. By screening a small-molecule kinase inhibitor library, we identified AKT as a kinase essential for robust SOX2 expression in OS cells. AKT was found to be frequently overexpressed in OS and positively correlated with SOX2 protein levels. We demonstrated that AKT has no effect on SOX2 transcription but promotes SOX2 protein stability. Mechanistically, AKT binds to and phosphorylates SOX2 at T116, preventing SOX2 ubiquitination and proteasome-dependent degradation by ubiquitin E3 ligases UBR5 and STUB1. Moreover, we found that AKT-SOX2 axis is a significant modulator of cancer stemness and chemoresistance and that the combination of AKT inhibitor MK2206 and cisplatin resulted in a synergistic and potent inhibition of OS tumor growth in the PDX model. In conclusion, we identified a critical role for AKT in promoting SOX2 overexpression, tumor stemness, and chemoresistance in OS, and provided evidence that targeting AKT combined with chemotherapy may hold promise for treating refractory OS.<figure>Working model showing that AKT stabilizes SOX2 by phosphorylating T116 site. Phosphorylation by AKT restraints the binding and ubiquitinoylation of SOX2 by the UBR5 and STUB1, thus promoting SOX2 stability and tumorigenic activity. Targeting AKT by MK2206 inhibits T116 phosphorylation and promotes SOX2 ubiquitination pathway, which impairs SOX2 tumorigenic activity. A combined treatment with chemo reagent and AKT inhibitor could achieve better therapeutic effect for SOX2-positive OS.</figure>","PeriodicalId":9134,"journal":{"name":"Bone Research","volume":"30 1","pages":""},"PeriodicalIF":12.7,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143477601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

CCN2 mediates fibroblast-macrophage interaction in knee arthrofibrosis based on single-cell RNA-seq analysis 基于单细胞RNA-seq分析的CCN2在膝关节纤维化中介导成纤维细胞与巨噬细胞的相互作用

IF 12.7 1区医学

Bone Research Pub Date : 2025-02-24 DOI: 10.1038/s41413-025-00400-9

Ziyun Li, Jia Jiang, Kangwen Cai, Yi Qiao, Xuancheng Zhang, Liren Wang, Yuhao Kang, Xiulin Wu, Benpeng Zhao, Xiuli Wang, Tianyi Zhang, Zhiqi Lin, Jinlong Wu, Simin Lu, Haihan Gao, Haocheng Jin, Caiqi Xu, Xiaoqiao Huangfu, Zhengzhi James, Qiuhua Chen, Xiaoqi Zheng, Ning-Ning Liu, Jinzhong Zhao

{"title":"CCN2 mediates fibroblast-macrophage interaction in knee arthrofibrosis based on single-cell RNA-seq analysis","authors":"Ziyun Li, Jia Jiang, Kangwen Cai, Yi Qiao, Xuancheng Zhang, Liren Wang, Yuhao Kang, Xiulin Wu, Benpeng Zhao, Xiuli Wang, Tianyi Zhang, Zhiqi Lin, Jinlong Wu, Simin Lu, Haihan Gao, Haocheng Jin, Caiqi Xu, Xiaoqiao Huangfu, Zhengzhi James, Qiuhua Chen, Xiaoqi Zheng, Ning-Ning Liu, Jinzhong Zhao","doi":"10.1038/s41413-025-00400-9","DOIUrl":"https://doi.org/10.1038/s41413-025-00400-9","url":null,"abstract":"Knee arthrofibrosis, characterized by excessive matrix protein production and deposition, substantially impairs basic daily functions, causing considerable distress and financial burden. However, the underlying pathomechanisms remain unclear. Here, we characterized the heterogeneous cell populations and cellular pathways by combination of flow cytometry and single-cell RNA-seq analysis of synovial tissues from six patients with or without knee arthrofibrosis. Increased macrophages and fibroblasts were observed with decreased numbers of fibroblast-like synoviocytes, endothelial cells, vascular smooth muscle cells, and T cells in the arthrofibrosis group compared with negative controls. Notably, fibroblasts were discovered to interact with macrophages, and lead to fibrosis through TGF-β pathway induced CCN2 expression in fibroblasts. CCN2 was demonstrated to be required for fibroblast pro-fibrotic functions (activation, proliferation, and migration) through TGFBR/SMAD pathway. The expression of CCN2 was positively correlated with the collagen volume and TGF-β expression and negatively associated with patient-reported outcome measures in another cohort of patients with knee arthrofibrosis. Our study reveals the role of CCN2 in the fibroblast-macrophage interaction through TGF-β pathway which might help to shed light on CCN2 as a potential biomarker.","PeriodicalId":9134,"journal":{"name":"Bone Research","volume":"66 1","pages":""},"PeriodicalIF":12.7,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143477534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

3D imaging reveals changes in the neurovascular architecture of the murine calvarium with aging 三维成像显示小鼠颅骨神经血管结构随年龄的变化

IF 12.7 1区医学

Bone Research Pub Date : 2025-02-21 DOI: 10.1038/s41413-025-00401-8

Allison L. Horenberg, Yunke Ren, Eric Z. Zeng, Alexandra N. Rindone, Arvind P. Pathak, Warren L. Grayson

{"title":"3D imaging reveals changes in the neurovascular architecture of the murine calvarium with aging","authors":"Allison L. Horenberg, Yunke Ren, Eric Z. Zeng, Alexandra N. Rindone, Arvind P. Pathak, Warren L. Grayson","doi":"10.1038/s41413-025-00401-8","DOIUrl":"https://doi.org/10.1038/s41413-025-00401-8","url":null,"abstract":"Calvarial nerves, along with vasculature, influence skull formation during development and following injury, but it remains unclear how calvarial nerves are spatially distributed during postnatal growth and aging. Studying the spatial distribution of nerves in the skull remains a challenge due to a lack of methods to quantify 3D structures in intact bone. To visualize calvarial 3D neurovascular architecture, we imaged nerves and endothelial cells with lightsheet microscopy. We employed machine-learning-based segmentation to facilitate high-resolution characterization from post-natal day 0 (P0) to 80 weeks. We found that TUBB3+ nerve density decreased with aging with the frontal bone demonstrating earlier onset age-related nerve loss than the parietal bone. In addition, nerves in the periosteum and dura mater exhibited similar yet distinct temporal patterns of nerve growth and loss. While no difference was observed in TUBB3+ nerves during skeletal maturation (P0 → 12 weeks), we did observe an increase in the volume of unmyelinated nerves in the dura mater. Regarding calvarial vasculature, larger CD31hiEmcn- vessel fraction increased with aging, while CD31hiEmcnhi vessel fraction was reduced. Throughout all ages, calvarial nerves maintained a preferential spatial association with CD31hiEmcnhi vessels, however, this association decreased with aging. Additionally, we used a model of Apert syndrome to explore the impact of suture-related disease on neurovascular architecture. Collectively, this 3D, spatiotemporal characterization of calvarial nerves throughout the lifespan and provides new insights into age-induced neurovascular architecture.","PeriodicalId":9134,"journal":{"name":"Bone Research","volume":"6 1","pages":""},"PeriodicalIF":12.7,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143462816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Matrix stiffness regulates nucleus pulposus cell glycolysis by MRTF-A-dependent mechanotransduction 基质刚度通过mrtf - a依赖的机械转导调节髓核细胞糖酵解

IF 12.7 1区医学

Bone Research Pub Date : 2025-02-14 DOI: 10.1038/s41413-025-00402-7

Haoran Xu, Kang Wei, Jinhao Ni, Xiaofeng Deng, Yuexing Wang, Taiyang Xiang, Fanglong Song, Qianliang Wang, Yanping Niu, Fengxian Jiang, Jun Wang, Lei Sheng, Jun Dai

{"title":"Matrix stiffness regulates nucleus pulposus cell glycolysis by MRTF-A-dependent mechanotransduction","authors":"Haoran Xu, Kang Wei, Jinhao Ni, Xiaofeng Deng, Yuexing Wang, Taiyang Xiang, Fanglong Song, Qianliang Wang, Yanping Niu, Fengxian Jiang, Jun Wang, Lei Sheng, Jun Dai","doi":"10.1038/s41413-025-00402-7","DOIUrl":"https://doi.org/10.1038/s41413-025-00402-7","url":null,"abstract":"Increased matrix stiffness of nucleus pulposus (NP) tissue is a main feature of intervertebral disc degeneration (IVDD) and affects various functions of nucleus pulposus cells (NPCs). Glycolysis is the main energy source for NPC survival, but the effects and underlying mechanisms of increased extracellular matrix (ECM) stiffness on NPC glycolysis remain unknown. In this study, hydrogels with different stiffness were established to mimic the mechanical environment of NPCs. Notably, increased matrix stiffness in degenerated NP tissues from IVDD patients was accompanied with impaired glycolysis, and NPCs cultured on rigid substrates exhibited a reduction in glycolysis. Meanwhile, RNA sequencing analysis showed altered cytoskeleton-related gene expression in NPCs on rigid substrates. Myocardin-related transcription factor A (MRTF-A) is a transcriptional coactivator in mechanotransduction mainly responding to cytoskeleton remodeling, which was activated and translocated to the nucleus under rigid substrate and was upregulated during IVDD progression. Furthermore, gas chromatography-mass spectrometry (GC-MS) analysis revealed that MRTF-A overexpression reduced NPC glycolytic metabolite abundance and identified a correlation with AMPK pathway. Mechanistically, rigid substrates and MRTF-A overexpression inhibited Kidins220 expression and AMPK phosphorylation in NPCs, whereas MRTF-A inhibition, treated with the MRTF-A inhibitor CCG, partially rescued NP tissue degeneration and glycolytic enzyme expression. Our data demonstrate that MRTF-A is a critical regulator that responds to increased matrix stiffness in IVDD, and MRTF-A activation reduces NPC glycolysis by down-regulating Kidins220 and inhibiting AMPK phosphorylation.","PeriodicalId":9134,"journal":{"name":"Bone Research","volume":"66 1","pages":""},"PeriodicalIF":12.7,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143417421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Photothermal sensitive nanocomposite hydrogel for infectious bone defects 光热敏感纳米复合水凝胶用于感染性骨缺损

IF 12.7 1区医学

Bone Research Pub Date : 2025-02-14 DOI: 10.1038/s41413-024-00377-x

Yanting Wu, Xi Xie, Guowen Luo, Jing Xie, Xiuwen Ye, Wanrong Gu, Anchun Mo, Zhiyong Qian, Chenchen Zhou, Jinfeng Liao

{"title":"Photothermal sensitive nanocomposite hydrogel for infectious bone defects","authors":"Yanting Wu, Xi Xie, Guowen Luo, Jing Xie, Xiuwen Ye, Wanrong Gu, Anchun Mo, Zhiyong Qian, Chenchen Zhou, Jinfeng Liao","doi":"10.1038/s41413-024-00377-x","DOIUrl":"https://doi.org/10.1038/s41413-024-00377-x","url":null,"abstract":"Infectious bone defects represent a substantial challenge in clinical practice, necessitating the deployment of advanced therapeutic strategies. This study presents a treatment modality that merges a mild photothermal therapy hydrogel with a pulsed drug delivery mechanism. The system is predicated on a hydrogel matrix that is thermally responsive, characteristic of bone defect sites, facilitating controlled and site-specific drug release. The cornerstone of this system is the incorporation of mild photothermal nanoparticles, which are activated within the temperature range of 40–43 °C, thereby enhancing the precision and efficacy of drug delivery. Our findings demonstrate that the photothermal response significantly augments the localized delivery of therapeutic agents, mitigating systemic side effects and bolstering efficacy at the defect site. The synchronized pulsed release, cooperated with mild photothermal therapy, effectively addresses infection control, and promotes bone regeneration. This approach signifies a considerable advancement in the management of infectious bone defects, offering an effective and patient-centric alternative to traditional methods. Our research endeavors to extend its applicability to a wider spectrum of tissue regeneration scenarios, underscoring its transformative potential in the realm of regenerative medicine.","PeriodicalId":9134,"journal":{"name":"Bone Research","volume":"28 12 1","pages":""},"PeriodicalIF":12.7,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143417422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Golgi-restored vesicular replenishment retards bone aging and empowers aging bone regeneration 高尔基恢复囊泡补充可延缓骨质老化并促进老化骨再生

IF 12.7 1区医学

Bone Research Pub Date : 2025-02-08 DOI: 10.1038/s41413-024-00386-w

Peisheng Liu, Hao Guo, Xiaoyao Huang, Anqi Liu, Ting Zhu, Chenxi Zheng, Fei Fu, Kaichao Zhang, Shijie Li, Xinyan Luo, Jiongyi Tian, Yan Jin, Kun Xuan, Bingdong Sui

{"title":"Golgi-restored vesicular replenishment retards bone aging and empowers aging bone regeneration","authors":"Peisheng Liu, Hao Guo, Xiaoyao Huang, Anqi Liu, Ting Zhu, Chenxi Zheng, Fei Fu, Kaichao Zhang, Shijie Li, Xinyan Luo, Jiongyi Tian, Yan Jin, Kun Xuan, Bingdong Sui","doi":"10.1038/s41413-024-00386-w","DOIUrl":"https://doi.org/10.1038/s41413-024-00386-w","url":null,"abstract":"Healthy aging is a common goal for humanity and society, and one key to achieving it is the rejuvenation of senescent resident stem cells and empowerment of aging organ regeneration. However, the mechanistic understandings of stem cell senescence and the potential strategies to counteract it remain elusive. Here, we reveal that the aging bone microenvironment impairs the Golgi apparatus thus diminishing mesenchymal stem cell (MSC) function and regeneration. Interestingly, replenishment of cell aggregates-derived extracellular vesicles (CA-EVs) rescues Golgi dysfunction and empowers senescent MSCs through the Golgi regulatory protein Syntaxin 5. Importantly, in vivo administration of CA-EVs significantly enhanced the bone defect repair rate and improved bone mass in aging mice, suggesting their therapeutic value for treating age-related osteoporosis and promoting bone regeneration. Collectively, our findings provide insights into Golgi regulation in stem cell senescence and bone aging, which further highlight CA-EVs as a potential rejuvenative approach for aging bone regeneration.","PeriodicalId":9134,"journal":{"name":"Bone Research","volume":"48 20 1","pages":""},"PeriodicalIF":12.7,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143367477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Nuclear farnesoid X receptor protects against bone loss by driving osteoblast differentiation through stabilizing RUNX2

IF 12.7 1区医学

Bone Research Pub Date : 2025-01-30 DOI: 10.1038/s41413-024-00394-w

Qi Dong, Haoyuan Fu, Wenxiao Li, Xinyu Ji, Yingchao Yin, Yiran Zhang, Yanbo Zhu, Guoqiang Li, Huiyang Jia, Heng Zhang, Haofei Wang, Jinglue Hu, Ganggang Wang, Zhihao Wu, Yingze Zhang, Sujuan Xu, Zhiyong Hou

{"title":"Nuclear farnesoid X receptor protects against bone loss by driving osteoblast differentiation through stabilizing RUNX2","authors":"Qi Dong, Haoyuan Fu, Wenxiao Li, Xinyu Ji, Yingchao Yin, Yiran Zhang, Yanbo Zhu, Guoqiang Li, Huiyang Jia, Heng Zhang, Haofei Wang, Jinglue Hu, Ganggang Wang, Zhihao Wu, Yingze Zhang, Sujuan Xu, Zhiyong Hou","doi":"10.1038/s41413-024-00394-w","DOIUrl":"https://doi.org/10.1038/s41413-024-00394-w","url":null,"abstract":"The delicate balance between bone formation by osteoblasts and bone resorption by osteoclasts maintains bone homeostasis. Nuclear receptors (NRs) are now understood to be crucial in bone physiology and pathology. However, the function of the Farnesoid X receptor (FXR), a member of the NR family, in regulating bone homeostasis remains incompletely understood. In this study, in vitro and in vivo models revealed delayed bone development and an osteoporosis phenotype in mice lacking FXR in bone marrow mesenchymal stem cells (BMSCs) and osteoblasts due to impaired osteoblast differentiation. Mechanistically, FXR could stabilize RUNX2 by inhibiting Thoc6-mediated ubiquitination, thereby promoting osteogenic activity in BMSCs. Moreover, activated FXR could directly bind to the Thoc6 promoter, suppressing its expression. The interaction between RUNX2 and Thoc6 was mediated by the Runt domain of RUNX2 and the WD repeat of Thoc6. Additionally, Obeticholic acid (OCA), an orally available FXR agonist, could ameliorate bone loss in an ovariectomy (OVX)-induced osteoporotic mouse model. Taken together, our findings suggest that FXR plays pivotal roles in osteoblast differentiation by regulating RUNX2 stability and that targeting FXR may be a promising therapeutic approach for osteoporosis.","PeriodicalId":9134,"journal":{"name":"Bone Research","volume":"4 1","pages":""},"PeriodicalIF":12.7,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143056500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Signaling pathway mechanisms of circadian clock gene Bmal1 regulating bone and cartilage metabolism: a review

IF 12.7 1区医学

Bone Research Pub Date : 2025-01-27 DOI: 10.1038/s41413-025-00403-6

Yiting Ze, Yongyao Wu, Zhen Tan, Rui Li, Rong Li, Wenzhen Gao, Qing Zhao

引用次数: 0