Bone Research最新文献_第3页

IGF2BP3-mediated m6A modification of RASGRF1 promoting joint injury in rheumatoid arthritis igf2bp3介导的m6A修饰促进类风湿性关节炎关节损伤

IF 12.7 1区医学

Bone Research Pub Date : 2025-05-12 DOI: 10.1038/s41413-025-00434-z

Qishun Geng, Yi Jiao, Wenya Diao, Jiahe Xu, Zhaoran Wang, Xing Wang, Zihan Wang, Lu Zhao, Lei Yang, Yilin Wang, Tingting Deng, Bailiang Wang, Cheng Xiao

{"title":"IGF2BP3-mediated m6A modification of RASGRF1 promoting joint injury in rheumatoid arthritis","authors":"Qishun Geng, Yi Jiao, Wenya Diao, Jiahe Xu, Zhaoran Wang, Xing Wang, Zihan Wang, Lu Zhao, Lei Yang, Yilin Wang, Tingting Deng, Bailiang Wang, Cheng Xiao","doi":"10.1038/s41413-025-00434-z","DOIUrl":"https://doi.org/10.1038/s41413-025-00434-z","url":null,"abstract":"With the deepening of epigenetic research, studies have shown that N6-methyladenosine (m6A) is closely related to the development of rheumatoid arthritis (RA), but the mechanism is still unclear. In the study, we collected synovial tissues from normal controls and patients with osteoarthritis (OA) or RA. The levels of m6A and inflammation were analyzed by immunofluorescence staining and western blotting. The roles of IGF2BP3 in cell proliferation and inflammatory activation were explored using transfection and RNA immunoprecipitation assays. IGF2BP3−/− mice were generated and used to establish an arthritis mouse model by transferring serum from adult arthritis K/BxN mice. We found m6A levels were markedly increased in RA patients and mouse models, and the expression of IGF2BP3 was upregulated in individuals with RA and related to the levels of inflammatory markers. IGF2BP3 played an important part in RA-fibroblast-like synoviocytes (FLS) by promoting cell proliferation, migration, invasion, inflammatory cytokine release and inhibiting autophagy. In addition, IGF2BP3 inhibited autophagy to reduce ROS production, thereby decreasing the inflammatory activation of macrophages. More importantly, RASGRF1-mediated mTORC1 activation played a crucial role in the ability of IGF2BP3 to promote cell proliferation and inflammatory activation. In an arthritis model of IGF2BP3−/− mice, IGF2BP3 knockout inhibited RA-FLS proliferation and inflammatory infiltration, and further ameliorated RA joint injury. Our study revealed an important role for IGF2BP3 in RA progression. The targeted inhibition of IGF2BP3 reduced cell proliferation and inflammatory activation and limited RA development, providing a potential strategy for RA therapy.","PeriodicalId":9134,"journal":{"name":"Bone Research","volume":"119 1","pages":""},"PeriodicalIF":12.7,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143933590","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

Sirt6 deficiency promotes senescence and age-associated intervertebral disc degeneration in mice Sirt6缺乏促进小鼠衰老和与年龄相关的椎间盘退变

IF 12.7 1区医学

Bone Research Pub Date : 2025-05-08 DOI: 10.1038/s41413-025-00422-3

Pranay Ramteke, Bahiyah Watson, Mallory Toci, Victoria A. Tran, Shira Johnston, Maria Tsingas, Ruteja A. Barve, Ramkrishna Mitra, Richard F. Loeser, John A. Collins, Makarand V. Risbud

{"title":"Sirt6 deficiency promotes senescence and age-associated intervertebral disc degeneration in mice","authors":"Pranay Ramteke, Bahiyah Watson, Mallory Toci, Victoria A. Tran, Shira Johnston, Maria Tsingas, Ruteja A. Barve, Ramkrishna Mitra, Richard F. Loeser, John A. Collins, Makarand V. Risbud","doi":"10.1038/s41413-025-00422-3","DOIUrl":"https://doi.org/10.1038/s41413-025-00422-3","url":null,"abstract":"Intervertebral disc degeneration is a major risk factor contributing to chronic low back and neck pain. While the etiological factors for disc degeneration vary, age is still one of the most important risk factors. Recent studies have shown the promising role of SIRT6 in mammalian aging and skeletal tissue health, however its role in the intervertebral disc health remains unexplored. We investigated the contribution of SIRT6 to disc health by studying the age-dependent spinal phenotype of mice with conditional deletion of Sirt6 in the disc (AcanCreERT2; Sirt6fl/fl). Histological studies showed a degenerative phenotype in knockout mice compared to Sirt6fl/fl control mice at 12 months, which became pronounced at 24 months. RNA-Seq analysis of NP and AF tissues, in vitro quantitative histone analysis, and RNA-seq with ATAC-seq multiomic studies revealed that SIRT6-loss resulted in changes in acetylation and methylation status of specific Histone 3 lysine residues and affected DNA accessibility and transcriptomic landscape. A decrease in autophagy and an increase in DNA damage were also noted in Sirt6-deficient cells. Further mechanistic insights revealed that loss of SIRT6 increased senescence and SASP burden in the disc characterized by increased p21, p19, γH2AX, IL-6, IL-1β, and TGF-β abundance. Taken together, our study highlights the contribution of SIRT6 in modulating DNA damage, autophagy, and cell senescence and its importance in maintaining disc health during aging, thereby underscoring it as a potential therapeutic target to treat intervertebral disc degeneration.","PeriodicalId":9134,"journal":{"name":"Bone Research","volume":"53 1","pages":""},"PeriodicalIF":12.7,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143920251","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

Bone-derived factors mediate crosstalk between skeletal and extra-skeletal organs 骨源性因子介导骨骼和骨骼外器官之间的串扰

IF 12.7 1区医学

Bone Research Pub Date : 2025-04-30 DOI: 10.1038/s41413-025-00424-1

Tailin He, Lei Qin, Sheng Chen, Shaochuan Huo, Jie Li, Fuping Zhang, Weihong Yi, Yifang Mei, Guozhi Xiao

{"title":"Bone-derived factors mediate crosstalk between skeletal and extra-skeletal organs","authors":"Tailin He, Lei Qin, Sheng Chen, Shaochuan Huo, Jie Li, Fuping Zhang, Weihong Yi, Yifang Mei, Guozhi Xiao","doi":"10.1038/s41413-025-00424-1","DOIUrl":"https://doi.org/10.1038/s41413-025-00424-1","url":null,"abstract":"Bone has long been acknowledged as a fundamental structural entity that provides support and protection to the body’s organs. However, emerging research indicates that bone plays a crucial role in the regulation of systemic metabolism. This is achieved through the secretion of a variety of hormones, cytokines, metal ions, extracellular vesicles, and other proteins/peptides, collectively referred to as bone-derived factors (BDFs). BDFs act as a medium through which bones can exert targeted regulatory functions upon various organs, thereby underscoring the profound and concrete implications of bone in human physiology. Nevertheless, there remains a pressing need for further investigations to elucidate the underlying mechanisms that inform the effects of bone on other body systems. This review aims to summarize the current findings related to the roles of these significant modulators across different organs and metabolic contexts by regulating critical genes and signaling pathways in vivo. It also addresses their involvement in the pathogenesis of various diseases affecting the musculoskeletal system, circulatory system, glucose and lipid metabolism, central nervous system, urinary system, and reproductive system. The insights gained from this review may contribute to the development of innovative therapeutic strategies through a focused approach to bone secretomes. Continued research into BDFs is expected to enhance our understanding of bone as a multifunctional organ with diverse regulatory roles in human health.","PeriodicalId":9134,"journal":{"name":"Bone Research","volume":"43 1","pages":""},"PeriodicalIF":12.7,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143889591","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

Advancing osteoarthritis research: the role of AI in clinical, imaging and omics fields 推进骨关节炎研究：人工智能在临床、成像和海洋学领域的作用

IF 12.7 1区医学

Bone Research Pub Date : 2025-04-22 DOI: 10.1038/s41413-025-00423-2

Jingfeng Ou, Jin Zhang, Momen Alswadeh, Zhenglin Zhu, Jijun Tang, Hongxun Sang, Ke Lu

{"title":"Advancing osteoarthritis research: the role of AI in clinical, imaging and omics fields","authors":"Jingfeng Ou, Jin Zhang, Momen Alswadeh, Zhenglin Zhu, Jijun Tang, Hongxun Sang, Ke Lu","doi":"10.1038/s41413-025-00423-2","DOIUrl":"https://doi.org/10.1038/s41413-025-00423-2","url":null,"abstract":"Osteoarthritis (OA) is a degenerative joint disease with significant clinical and societal impact. Traditional diagnostic methods, including subjective clinical assessments and imaging techniques such as X-rays and MRIs, are often limited in their ability to detect early-stage OA or capture subtle joint changes. These limitations result in delayed diagnoses and inconsistent outcomes. Additionally, the analysis of omics data is challenged by the complexity and high dimensionality of biological datasets, making it difficult to identify key molecular mechanisms and biomarkers. Recent advancements in artificial intelligence (AI) offer transformative potential to address these challenges. This review systematically explores the integration of AI into OA research, focusing on applications such as AI-driven early screening and risk prediction from electronic health records (EHR), automated grading and morphological analysis of imaging data, and biomarker discovery through multi-omics integration. By consolidating progress across clinical, imaging, and omics domains, this review provides a comprehensive perspective on how AI is reshaping OA research. The findings have the potential to drive innovations in personalized medicine and targeted interventions, addressing longstanding challenges in OA diagnosis and management.","PeriodicalId":9134,"journal":{"name":"Bone Research","volume":"6 1","pages":""},"PeriodicalIF":12.7,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143857471","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

SPI1 activates mitochondrial unfolded response signaling to inhibit chondrocyte senescence and relieves osteoarthritis SPI1激活线粒体未折叠反应信号，抑制软骨细胞衰老，缓解骨关节炎

IF 12.7 1区医学

Bone Research Pub Date : 2025-04-14 DOI: 10.1038/s41413-025-00421-4

Xiangyu Zu, Shenghong Chen, Zhengyuan Li, Lin Hao, Wenhan Fu, Hui Zhang, Zongsheng Yin, Yin Wang, Jun Wang

{"title":"SPI1 activates mitochondrial unfolded response signaling to inhibit chondrocyte senescence and relieves osteoarthritis","authors":"Xiangyu Zu, Shenghong Chen, Zhengyuan Li, Lin Hao, Wenhan Fu, Hui Zhang, Zongsheng Yin, Yin Wang, Jun Wang","doi":"10.1038/s41413-025-00421-4","DOIUrl":"https://doi.org/10.1038/s41413-025-00421-4","url":null,"abstract":"Chondrocyte senescence is a critical pathological hallmark of osteoarthritis (OA). Aberrant mechanical stress is considered a pivotal determinant in chondrocyte aging; however, the precise underlying mechanism remains elusive. Our findings demonstrate that SPI1 plays a significant role in counteracting chondrocyte senescence and inhibiting OA progression. SPI1 binds to the PERK promoter, thereby promoting its transcriptional activity. Importantly, PERK, rather than GCN2, facilitates eIF2α phosphorylation, activating the mitochondrial unfolded protein response (UPRmt) and impeding chondrocyte senescence. Deficiency of SPI1 in mechanical overload-induced mice leads to diminished UPRmt activation and accelerated OA progression. Intra-articular injection of adenovirus vectors overexpressing SPI1 and PERK effectively mitigates cartilage degeneration. In summary, our study elucidates the crucial regulatory role of SPI1 in the pathogenesis of chondrocyte senescence by activating UPRmt signaling through PERK, which may present a novel therapeutic target for treating OA.<figure>SPI1 alleviates the progression of OA by inhibiting mechanical stress-induced chondrocyte senescence through mitochondrial UPR signaling.</figure>","PeriodicalId":9134,"journal":{"name":"Bone Research","volume":"40 1","pages":""},"PeriodicalIF":12.7,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143827656","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

NELL2, a novel osteoinductive factor, regulates osteoblast differentiation and bone homeostasis through fibronectin 1/integrin-mediated FAK/AKT signaling NELL2是一种新型的骨诱导因子，通过纤维连接蛋白1/整合素介导的FAK/AKT信号传导调节成骨细胞分化和骨稳态

IF 12.7 1区医学

Bone Research Pub Date : 2025-04-11 DOI: 10.1038/s41413-025-00420-5

Hairui Yuan, Xinyu Wang, Shuanglin Du, Mengyue Li, Endong Zhu, Jie Zhou, Yuan Dong, Shuang Wang, Liying Shan, Qian Liu, Baoli Wang

{"title":"NELL2, a novel osteoinductive factor, regulates osteoblast differentiation and bone homeostasis through fibronectin 1/integrin-mediated FAK/AKT signaling","authors":"Hairui Yuan, Xinyu Wang, Shuanglin Du, Mengyue Li, Endong Zhu, Jie Zhou, Yuan Dong, Shuang Wang, Liying Shan, Qian Liu, Baoli Wang","doi":"10.1038/s41413-025-00420-5","DOIUrl":"https://doi.org/10.1038/s41413-025-00420-5","url":null,"abstract":"Neural EGFL-like 2 (NELL2) is a secreted protein known for its regulatory functions in the nervous and reproductive systems, yet its role in bone biology remains unexplored. In this study, we observed that NELL2 was diminished in the bone of aged and ovariectomized (OVX) mice, as well as in the serum of osteopenia and osteoporosis patients. In vitro loss-of-function and gain-of-function studies revealed that NELL2 facilitated osteoblast differentiation and impeded adipocyte differentiation from stromal progenitor cells. In vivo studies further demonstrated that the deletion of NELL2 in preosteoblasts resulted in decreased cancellous bone mass in mice. Mechanistically, NELL2 interacted with the FNI-type domain located at the C-terminus of Fibronectin 1 (Fn1). Moreover, we found that NELL2 activated the focal adhesion kinase (FAK)/AKT signaling pathway through Fn1/integrin β1 (ITGB1), leading to the promotion of osteogenesis and the inhibition of adipogenesis. Notably, administration of NELL2-AAV was found to ameliorate bone loss in OVX mice. These findings underscore the significant role of NELL2 in osteoblast differentiation and bone homeostasis, suggesting its potential as a therapeutic target for managing osteoporosis.","PeriodicalId":9134,"journal":{"name":"Bone Research","volume":"16 1","pages":""},"PeriodicalIF":12.7,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143819475","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

Cell communication and relevant signaling pathways in osteogenesis–angiogenesis coupling 骨生成-血管生成耦合中的细胞通讯及相关信号通路

IF 12.7 1区医学

Bone Research Pub Date : 2025-04-07 DOI: 10.1038/s41413-025-00417-0

Shuqing Li, Xinjia Cai, Jiahe Guo, Xiaolu Li, Wen Li, Yan Liu, Mengchun Qi

{"title":"Cell communication and relevant signaling pathways in osteogenesis–angiogenesis coupling","authors":"Shuqing Li, Xinjia Cai, Jiahe Guo, Xiaolu Li, Wen Li, Yan Liu, Mengchun Qi","doi":"10.1038/s41413-025-00417-0","DOIUrl":"https://doi.org/10.1038/s41413-025-00417-0","url":null,"abstract":"Osteogenesis is the process of bone formation mediated by the osteoblasts, participating in various bone-related physiological processes including bone development, bone homeostasis and fracture healing. It exhibits temporal and spatial interconnectivity with angiogenesis, constructed by multiple forms of cell communication occurring between bone and vascular endothelial cells. Molecular regulation among different cell types is crucial for coordinating osteogenesis and angiogenesis to facilitate bone remodeling, fracture healing, and other bone-related processes. The transmission of signaling molecules and the activation of their corresponding signal pathways are indispensable for various forms of cell communication. This communication acts as a “bridge” in coupling osteogenesis to angiogenesis. This article reviews the modes and processes of cell communication in osteogenesis-angiogenesis coupling over the past decade, mainly focusing on interactions among bone-related cells and vascular endothelial cells to provide insights into the mechanism of cell communication of osteogenesis-angiogenesis coupling in different bone-related contexts. Moreover, clinical relevance and applications are also introduced in this review.","PeriodicalId":9134,"journal":{"name":"Bone Research","volume":"38 1","pages":""},"PeriodicalIF":12.7,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143790156","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

Porcupine inhibition is a promising pharmacological treatment for severe sclerosteosis pathologies 豪猪抑制是一种有前途的药物治疗严重的硬化症病理

IF 12.7 1区医学

Bone Research Pub Date : 2025-04-07 DOI: 10.1038/s41413-025-00406-3

Timothy J. Dreyer, Jacob A. C. Keen, Leah M. Wells, Mark Hopkinson, Isabel R. Orriss, Gill Holdsworth, Andrew A. Pitsillides, Scott J. Roberts

{"title":"Porcupine inhibition is a promising pharmacological treatment for severe sclerosteosis pathologies","authors":"Timothy J. Dreyer, Jacob A. C. Keen, Leah M. Wells, Mark Hopkinson, Isabel R. Orriss, Gill Holdsworth, Andrew A. Pitsillides, Scott J. Roberts","doi":"10.1038/s41413-025-00406-3","DOIUrl":"https://doi.org/10.1038/s41413-025-00406-3","url":null,"abstract":"Sclerosteosis, an ultra-rare disorder characterised by high bone mass (HBM) and skeletal overgrowth, leads to facial paralysis, hearing loss and raised intracranial pressure, which is currently managed only through high-risk surgery. Sclerosteosis is caused by SOST mutations and loss of functional sclerostin, a protein that suppresses osteogenesis by antagonising Wnt/β-catenin signalling. Herein, using in vitro and in vivo approaches, we explore whether LGK974, another potent Wnt inhibitor that targets porcupine (PORCN, Wnt-specific acyltransferase), is a promising sclerosteosis therapeutic. In vitro assays showed that 100 nmol/L LGK974 significantly reduced osteoblast alkaline phosphatase (ALP) activity/mineralisation, decreased Wnt/osteoblast marker (Axin2, Runx2 and Ocn) expression, and downregulated ossification and the Wnt signalling pathway, without affecting osteoclast numbers/resorption. To assess in vivo effects, 6-week-old male and female Sost deficient (Sost-/-) mice received LGK974 for 4 weeks and right hindlimbs were subjected to 20 N peak loading to assess mechanoadaptive interactions. µCT revealed significant reductions in vertebral trabecular number and lower cortical bone volume in loaded and non-loaded tibiae in male and female LGK974-treated Sost-/- mice. Interestingly, the target engagement biomarker Axin2 was only significantly reduced in male vertebrae, which may indicate differences in male and female response to LGK974. This study also shows that PORCN inhibition may effectively limit characteristic HBM and skeletal overgrowth in sclerosteosis patients at sites with severe pathology.","PeriodicalId":9134,"journal":{"name":"Bone Research","volume":"217 1","pages":""},"PeriodicalIF":12.7,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143790159","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

KIAA1199 (CEMIP) regulates adipogenesis and whole-body energy metabolism KIAA1199 （CEMIP）调节脂肪生成和全身能量代谢

IF 12.7 1区医学

Bone Research Pub Date : 2025-04-02 DOI: 10.1038/s41413-025-00415-2

Li Chen, Kaikai Shi, Nicholas Ditzel, Weimin Qiu, Michaela Tencerova, Louise Himmelstrup Dreyer Nielsen, Florence Figeac, Alexander Rauch, Yuhang Liu, Jiuyuan Tao, Veronika Sramkova, Lenka Rossmeislova, Greet Kerckhofs, Tatjana N. Parac-Vogt, Sébastien de Bournonville, Thomas Levin Andersen, Mikael Rydén, Moustapha Kassem

{"title":"KIAA1199 (CEMIP) regulates adipogenesis and whole-body energy metabolism","authors":"Li Chen, Kaikai Shi, Nicholas Ditzel, Weimin Qiu, Michaela Tencerova, Louise Himmelstrup Dreyer Nielsen, Florence Figeac, Alexander Rauch, Yuhang Liu, Jiuyuan Tao, Veronika Sramkova, Lenka Rossmeislova, Greet Kerckhofs, Tatjana N. Parac-Vogt, Sébastien de Bournonville, Thomas Levin Andersen, Mikael Rydén, Moustapha Kassem","doi":"10.1038/s41413-025-00415-2","DOIUrl":"https://doi.org/10.1038/s41413-025-00415-2","url":null,"abstract":"An increasing number of studies have characterized the bone as an endocrine organ, and that bone secreted factors may not only regulate local bone remodeling, but also other tissues and whole-body metabolic functions. The precise nature of these regulatory factors and their roles at bridging the bone, bone marrow adipose tissue, extramedullary body fat and whole-body energy homeostasis are being explored. In this study, we report that KIAA1199, a secreted factor produced from bone and bone marrow, previously described as an inhibitor of bone formation, also plays a role at promoting adipogenesis. KIAA1199-deficient mice exhibit reduced bone marrow adipose tissue, subcutaneous and visceral fat tissue mass, blood cholesterol, triglycerides, free fatty acids and glycerol, as well as improved insulin sensitivity in skeletal muscle, liver and fat. Moreover, these mice are protected from the detrimental effects of high-fat diet feeding, with decreased obesity, lower blood glucose and glucose tolerance, as well as decreased adipose tissue inflammation, insulin resistance and hepatic steatosis. In human studies, plasma levels of KIAA1199 or its expression levels in adipose tissue are positively correlated with insulin resistance and blood levels of cholesterol, triglycerides, free fatty acids, glycerol, fasting glucose and HOMA-IR. Mechanistically, KIAA1199 mediates its effects on adipogenesis through modulating osteopontin-integrin and AKT / ERK signaling. These findings provide evidence for the role of bone secreted factors on coupling bone, fat and whole-body energy homeostasis.","PeriodicalId":9134,"journal":{"name":"Bone Research","volume":"104 1","pages":""},"PeriodicalIF":12.7,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143758097","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

M2 macrophages-derived exosomes for osteonecrosis of femoral head treatment: modulating neutrophil extracellular traps formation and endothelial phenotype transition M2巨噬细胞衍生外泌体治疗股骨头坏死：调节中性粒细胞胞外陷阱形成和内皮表型转变

IF 12.7 1区医学

Bone Research Pub Date : 2025-04-01 DOI: 10.1038/s41413-025-00412-5

Guanzhi Liu, Ruomu Cao, Qimeng Liu, Heng Li, Peng Yan, Kunzheng Wang, Run Tian, Pei Yang

{"title":"M2 macrophages-derived exosomes for osteonecrosis of femoral head treatment: modulating neutrophil extracellular traps formation and endothelial phenotype transition","authors":"Guanzhi Liu, Ruomu Cao, Qimeng Liu, Heng Li, Peng Yan, Kunzheng Wang, Run Tian, Pei Yang","doi":"10.1038/s41413-025-00412-5","DOIUrl":"https://doi.org/10.1038/s41413-025-00412-5","url":null,"abstract":"Exosomes have shown good potential in ischemic injury disease treatments. However, evidence about their effect and molecular mechanisms in osteonecrosis of femoral head (ONFH) treatment is still limited. Here, we revealed the cell biology characters of ONFH osteonecrosis area bone tissue in single cell scale and thus identified a novel ONFH treatment approach based on M2 macrophages-derived exosomes (M2-Exos). We further show that M2-Exos are highly effective in the treatment of ONFH by modulating the phenotypes communication between neutrophil and endothelium including neutrophil extracellular traps formation and endothelial phenotype transition. Additionally, we identified that M2-Exos’ therapeutic effect is attributed to the high content of miR-93-5p and constructed miR-93-5p overexpression model in vitro and in vivo based on lentivirus and adeno-associated virus respectively. Then we found miR-93-5p can not only reduce neutrophil extracellular traps formation but also improve angiogenic ability of endothelial cells. These results provided a new theoretical basis for the clinical application of ONFH therapeutic exosomes.","PeriodicalId":9134,"journal":{"name":"Bone Research","volume":"33 1","pages":""},"PeriodicalIF":12.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143744752","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