Bone Research最新文献

The impact of mitochondrial dysfunction on osteoarthritis cartilage: current insights and emerging mitochondria-targeted therapies 线粒体功能障碍对骨关节炎软骨的影响：当前的见解和新兴的线粒体靶向治疗

IF 12.7 1区医学

Bone Research Pub Date : 2025-09-01 DOI: 10.1038/s41413-025-00460-x

Siyuan Tan, Yujun Sun, Shixun Li, Haoyu Wu, Yue Ding

{"title":"The impact of mitochondrial dysfunction on osteoarthritis cartilage: current insights and emerging mitochondria-targeted therapies","authors":"Siyuan Tan, Yujun Sun, Shixun Li, Haoyu Wu, Yue Ding","doi":"10.1038/s41413-025-00460-x","DOIUrl":"https://doi.org/10.1038/s41413-025-00460-x","url":null,"abstract":"Osteoarthritis (OA) is a degenerative joint disease associated with age, prominently marked by articular cartilage degradation. In OA cartilage, the pathological manifestations show elevated chondrocyte hypertrophy and apoptosis. The mitochondrion serves as key energy supporter in eukaryotic cells and is tightly linked to a myriad of diseases including OA. As age advances, mitochondrial function declines progressively, which leads to an imbalance in chondrocyte energy homeostasis, partially initiating the process of cartilage degeneration. Elevated oxidative stress, impaired mitophagy and mitochondrial dynamics jointly contribute to chondrocyte pathology, with mitochondrial DNA haplogroups, particularly haplogroup J, influencing OA progression. Therapeutic approaches directed at mitochondria have demonstrated remarkable efficacy in treating various diseases, with triphenylphosphonium (TPP) emerging as the most widely utilized molecule. Other strategies encompass Dequalinium (DQA), the Szeto-Schiller (SS) tetrapeptide family, the KLA peptide, and mitochondrial-penetrating peptides (MPP), etc. These molecules share common properties of lipophilicity and positive charge. Through various technological modifications, they are conjugated to nanocarriers, enabling targeted drug delivery to mitochondria. Therapeutic interventions targeting mitochondria offer a hopeful direction for OA treatment. In the future, mitochondria-targeted therapy is anticipated to improve the well-being of life for the majority of OA patients. This review summarizes the link between chondrocyte mitochondrial dysfunction and OA, as well as discusses promising mitochondria-targeted therapies and potential therapeutic compounds.","PeriodicalId":9134,"journal":{"name":"Bone Research","volume":"26 1","pages":""},"PeriodicalIF":12.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144923920","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

The role of the unfolded protein response pathway in bone homeostasis and potential therapeutic target in cancer-associated bone disease 未折叠蛋白反应通路在骨稳态中的作用及癌症相关骨病的潜在治疗靶点

IF 12.7 1区医学

Bone Research Pub Date : 2025-08-28 DOI: 10.1038/s41413-025-00457-6

Molly E. Muehlebach, Sarah A. Holstein

{"title":"The role of the unfolded protein response pathway in bone homeostasis and potential therapeutic target in cancer-associated bone disease","authors":"Molly E. Muehlebach, Sarah A. Holstein","doi":"10.1038/s41413-025-00457-6","DOIUrl":"https://doi.org/10.1038/s41413-025-00457-6","url":null,"abstract":"The unfolded protein response pathway is an evolutionarily conserved cytoprotective signaling cascade, essential for cell function and survival. Unfolded protein response signaling is tightly integrated with bone cell differentiation and function, and chronic unfolded protein response activation has been identified in bone disease. The unfolded protein response has been found to promote oncogenesis and drug resistance, raising the possibility that unfolded protein response modulators may have activity as anti-cancer agents. Cancer-associated bone disease remains a major cause of morbidity for patients with multiple myeloma or bone-metastatic disease. Understanding the critical role of unfolded protein response signaling in cancer development and metastasis, as well as its role in bone homeostasis, may lead to novel mechanisms by which to target cancer-associated bone disease. In this review, we summarize the current research delineating the roles of the unfolded protein response in bone biology and pathophysiology, and furthermore, review unfolded protein response modulating agents in the contexts of cancer and cancer-associated bone disease.","PeriodicalId":9134,"journal":{"name":"Bone Research","volume":"6 1","pages":""},"PeriodicalIF":12.7,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144911195","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

Association between osteoporosis and rotator cuff tears: evidence from causal inference and colocalization analyses 骨质疏松症和肩袖撕裂之间的关系：来自因果推理和共定位分析的证据

IF 12.7 1区医学

Bone Research Pub Date : 2025-08-28 DOI: 10.1038/s41413-025-00450-z

Yibin Liu, Rong Zhao, Zhiyu Huang, Feifei Li, Xing Li, Kaixin Zhou, Kathleen A. Derwin, Xiaofei Zheng, Hongmin Cai, Jinjin Ma

{"title":"Association between osteoporosis and rotator cuff tears: evidence from causal inference and colocalization analyses","authors":"Yibin Liu, Rong Zhao, Zhiyu Huang, Feifei Li, Xing Li, Kaixin Zhou, Kathleen A. Derwin, Xiaofei Zheng, Hongmin Cai, Jinjin Ma","doi":"10.1038/s41413-025-00450-z","DOIUrl":"https://doi.org/10.1038/s41413-025-00450-z","url":null,"abstract":"Osteoporosis is a known risk factor for rotator cuff tears (RCTs), but the causal correlation and underlying mechanisms remain unclear. This study aims to evaluate the impact of osteoporosis on RCT risk and investigate their genetic associations. Using data from the UK Biobank (n = 457 871), cross-sectional analyses demonstrated that osteoporosis was significantly associated with an increased risk of RCTs (adjusted OR [95% CI] = 1.38 [1.25–1.52]). A longitudinal analysis of a subset of patients (n = 268 117) over 11 years revealed that osteoporosis increased the risk of RCTs (adjusted HR [95% CI] = 1.56 [1.29–1.87]), which is notably varied between sexes in sex-stratified analysis. Causal inference methods, including propensity score matching, inverse probability weighting, causal random forest and survival random forest models further confirmed the causal effect, both from cross-sectional and longitudinal perspectives. A colocalization analysis across multiple datasets identified six candidate loci, including the successfully replicated PKDCC rs12996954 variant, which may help explain the shared genetic basis between osteoporosis and RCTs. In conclusion, osteoporosis significantly increases the risk of RCTs, emphasizing the importance of osteoporosis management in preventing RCTs. The identification of shared genetic loci provides new insights into their potential pathogenic mechanisms.","PeriodicalId":9134,"journal":{"name":"Bone Research","volume":"24 1","pages":""},"PeriodicalIF":12.7,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144911199","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

Chemotherapeutic drug-triggered AEP-cleaved G3BP1 orchestrates stress granules/nucleoli/mitochondria in osteosarcoma 化疗药物引发的aep裂解G3BP1调控骨肉瘤中的应激颗粒/核仁/线粒体

IF 12.7 1区医学

Bone Research Pub Date : 2025-08-26 DOI: 10.1038/s41413-025-00453-w

Zhonggang Shi, Jianyi Zhao, Qi Lv, Keman Liao, Lu Cao, Jian Yang, Mengying Wang, Li Zhou, Haoping Xu, Jianwei Ge, Yongming Qiu, Juxiang Chen, Jiayi Chen, Chunhui Ma, Yingying Lin

{"title":"Chemotherapeutic drug-triggered AEP-cleaved G3BP1 orchestrates stress granules/nucleoli/mitochondria in osteosarcoma","authors":"Zhonggang Shi, Jianyi Zhao, Qi Lv, Keman Liao, Lu Cao, Jian Yang, Mengying Wang, Li Zhou, Haoping Xu, Jianwei Ge, Yongming Qiu, Juxiang Chen, Jiayi Chen, Chunhui Ma, Yingying Lin","doi":"10.1038/s41413-025-00453-w","DOIUrl":"https://doi.org/10.1038/s41413-025-00453-w","url":null,"abstract":"Osteosarcoma (OS) is the most frequent primary bone sarcomas with high recurrence and poor prognosis. Emerging evidence indicates that membraneless organelles stress granules (SGs), whose assemblies are driven by scaffold protein G3BP1, are extensively involved in tumor, especially in OS. However, how SGs behave and communicate with organelles, particularly nucleoli and mitochondria, during drug challenges remain unknown. This study revealed that chemotherapeutic drugs activated the cysteine protease asparagine endopeptidase (AEP) to specifically cleave the SG core protein G3BP1 at N258/N309 in OS and malignant glioma. tG3BP1-Ns modulated SG dynamics by competitively binding to full-length G3BP1. Strikingly, tG3BP1-Cs, containing a conserved RNA recognition motif CCUBSCUS, sequestered mRNAs of ribosomal proteins and oxidative phosphorylation genes in the nucleoli and mitochondria to repress translation and oxidative stress. Moreover, the inhibition of AEP promoted the tumor-suppressing effect of chemotherapeutic drugs, whereas AEP-cleaved G3BP1 rescue reversed the effect in both OS and glioma models. Cancerous tissues exhibited high levels of AEP and G3BP1 truncations, which were strongly associated with poor prognosis. Accordingly, this study proposed a new paradigm and potential therapeutic targets to address chemotherapy sensitivity conferred by AEP-cleaved G3BP1-mediated SGs/nucleoli/mitochondria coordination.<figure></figure>","PeriodicalId":9134,"journal":{"name":"Bone Research","volume":"26 1","pages":""},"PeriodicalIF":12.7,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144901863","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

Osteocytic vinculin controls bone mass by modulating Mef2c-driven sclerostin expression in mice 骨细胞血管素通过调节mef2c驱动的硬化蛋白表达来控制小鼠骨量

IF 12.7 1区医学

Bone Research Pub Date : 2025-08-13 DOI: 10.1038/s41413-025-00452-x

Yishu Wang, Jianmei Huang, Sixiong Lin, Lei Qin, Dingyu Hao, Peijun Zhang, Shaochuan Huo, Xuenong Zou, Di Chen, Guozhi Xiao

{"title":"Osteocytic vinculin controls bone mass by modulating Mef2c-driven sclerostin expression in mice","authors":"Yishu Wang, Jianmei Huang, Sixiong Lin, Lei Qin, Dingyu Hao, Peijun Zhang, Shaochuan Huo, Xuenong Zou, Di Chen, Guozhi Xiao","doi":"10.1038/s41413-025-00452-x","DOIUrl":"https://doi.org/10.1038/s41413-025-00452-x","url":null,"abstract":"The focal adhesion (FA) is the structural basis of the cell-extracellular matrix crosstalk and plays important roles in control of organ formation and function. Here we show that expression of FA protein vinculin is dramatically reduced in osteocytes in patients with aging-related osteoporosis. Vinculin loss severely impaired osteocyte adhesion and dendrite formation. Deleting vinculin using the mouse 10-kb Dmp1-Cre transgenic mice causes dramatic bone loss in the weight-bearing long bones and spine, but not in the skull, in both young and aged mice by impairing osteoblast formation and function without markedly affecting bone resorption. Vinculin loss impairs the anabolic response of skeleton to mechanical loading in mice. Vinculin knockdown increases, while vinculin overexpression decreases, sclerostin expression in osteocytes without impacting expression of Mef2c, a major transcriptional regulator of the Sost gene, which encodes sclerostin. Vinculin interacts with Mef2c and retains the latter in the cytoplasm. Thus, vinculin loss enhances Mef2c nuclear translocation and binding to the Sost enhancer ECR5 to promote sclerostin expression in osteocytes and reduces bone formation. Consistent with this notion, deleting Sost expression in osteocytes reverses the osteopenic phenotypes caused by vinculin loss in mice. Finally, we find that estrogen is a novel regulator of vinculin expression in osteocytes and that vinculin-deficient mice are resistant to ovariectomy-induced bone loss. Thus, we demonstrate a novel mechanism through which vinculin inhibits the Mef2c-driven sclerostin expression in osteocytes to promote bone formation.","PeriodicalId":9134,"journal":{"name":"Bone Research","volume":"8 1","pages":""},"PeriodicalIF":12.7,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144825133","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

The mitochondrial E3 ligase MAPL SUMOylates Drp1 to facilitate mitochondrial fission in intervertebral disc degeneration 线粒体E3连接酶MAPL sumoylate Drp1促进椎间盘退变过程中的线粒体裂变

IF 12.7 1区医学

Bone Research Pub Date : 2025-08-12 DOI: 10.1038/s41413-025-00449-6

Zhidi Lin, Xiao Lu, Guangyu Xu, Jian Song, Hongli Wang, Xinlei Xia, Feizhou Lu, Jianyuan Jiang, Wei Zhu, Zuochong Yu, Xiaosheng Ma, Fei Zou

{"title":"The mitochondrial E3 ligase MAPL SUMOylates Drp1 to facilitate mitochondrial fission in intervertebral disc degeneration","authors":"Zhidi Lin, Xiao Lu, Guangyu Xu, Jian Song, Hongli Wang, Xinlei Xia, Feizhou Lu, Jianyuan Jiang, Wei Zhu, Zuochong Yu, Xiaosheng Ma, Fei Zou","doi":"10.1038/s41413-025-00449-6","DOIUrl":"https://doi.org/10.1038/s41413-025-00449-6","url":null,"abstract":"Intervertebral disc degeneration (IVDD) is the primary contributor to a range of spinal diseases. Dynamin-related protein 1 (Drp1)-mediated mitochondrial fission has recently been identified as a new cause of nucleus pulposus cell (NPC) death and IVDD, but the underlying mechanisms remain unclear. Although the effects of Drp1 phosphorylation in IVDD have been studied, it is currently unknown if small ubiquitin-like modifications (SUMOylation) of Drp1 regulate IVDD. This study aimed to investigate the functions and mechanisms of mitochondria-anchored protein ligase (MAPL), a mitochondrial SUMO E3 ligase, during IVDD progression. The expression of genes related to SUMOylation and mitochondrial dynamics in TNF-α-stimulated NPCs was analysed via RNA sequencing. The levels of total and mitochondrial SUMO1 conjugates were elevated with MAPL upregulation in TNF-α-treated NPCs. Additionally, mitochondrial fragmentation and dysfunction were induced by TNF-α stimulation. MAPL overexpression promoted mitochondrial SUMOylation and SUMO1 modification of Drp1, thereby facilitating the mitochondrial translocation of Drp1 and mitochondrial fission. MAPL-induced ROS accumulation and ΔΨm loss led to increased NPC apoptosis. Mutation of the SUMO-acceptor lysine residues of Drp1 hindered its SUMOylation and rescued the mitochondrial phenotypes caused by MAPL. SENP5 overexpression phenocopied MAPL silencing, negatively modulating the SUMO1 modification of Drp1 and mitochondrial fission in NPCs. In a rat IVDD model, forced expression of MAPL by using an adeno-associated virus (AAV) vector aggravated IVD tissue damage, whereas the knockdown of MAPL delayed IVDD progression. Our findings highlight the importance of SUMOylation in IVDD. The inhibition of MAPL-mediated Drp1 SUMOylation alleviates mitochondrial fission and limits IVDD development, providing a potential strategy for IVDD treatment.<figure></figure>","PeriodicalId":9134,"journal":{"name":"Bone Research","volume":"38 1","pages":""},"PeriodicalIF":12.7,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144819224","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

Nucleic acid aptamers in orthopedic diseases: promising therapeutic agents for bone disorders 核酸适体在骨科疾病中的应用：有希望的骨疾病治疗剂

IF 12.7 1区医学

Bone Research Pub Date : 2025-07-24 DOI: 10.1038/s41413-025-00447-8

Zhenhong He, Qingping Peng, Wenying Bin, Luyao Zhao, Yihuang Chen, Yuanqun Zhang, Weihu Yang, Xingchen Yan, Huan Liu

{"title":"Nucleic acid aptamers in orthopedic diseases: promising therapeutic agents for bone disorders","authors":"Zhenhong He, Qingping Peng, Wenying Bin, Luyao Zhao, Yihuang Chen, Yuanqun Zhang, Weihu Yang, Xingchen Yan, Huan Liu","doi":"10.1038/s41413-025-00447-8","DOIUrl":"https://doi.org/10.1038/s41413-025-00447-8","url":null,"abstract":"Precision medicine has become a cornerstone in modern therapeutic strategies, with nucleic acid aptamers emerging as pivotal tools due to their unique properties. These oligonucleotide fragments, selected through the Systematic Evolution of Ligands by Exponential Enrichment process, exhibit high affinity and specificity toward their targets, such as DNA, RNA, proteins, and other biomolecules. Nucleic acid aptamers offer significant advantages over traditional therapeutic agents, including superior biological stability, minimal immunogenicity, and the capacity for universal chemical modifications that enhance their in vivo performance and targeting precision. In the realm of osseous tissue repair and regeneration, a complex physiological process essential for maintaining skeletal integrity, aptamers have shown remarkable potential in influencing molecular pathways crucial for bone regeneration, promoting osteogenic differentiation and supporting osteoblast survival. By engineering aptamers to regulate inflammatory responses and facilitate the proliferation and differentiation of fibroblasts, these oligonucleotides can be integrated into advanced drug delivery systems, significantly improving bone repair efficacy while minimizing adverse effects. Aptamer-mediated strategies, including the use of siRNA and miRNA mimics or inhibitors, have shown efficacy in enhancing bone mass and microstructure. These approaches hold transformative potential for treating a range of orthopedic conditions like osteoporosis, osteosarcoma, and osteoarthritis. This review synthesizes the molecular mechanisms and biological roles of aptamers in orthopedic diseases, emphasizing their potential to drive innovative and effective therapeutic interventions.","PeriodicalId":9134,"journal":{"name":"Bone Research","volume":"16 1","pages":""},"PeriodicalIF":12.7,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144694217","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

Osteoclast-independent osteocyte dendrite defects in mice bearing the osteogenesis imperfecta-causing Sp7 R342C mutation. 携带成骨不完全引起的Sp7 R342C突变的小鼠的破骨细胞不依赖骨细胞树突缺陷。

IF 12.7 1区医学

Bone Research Pub Date : 2025-07-19 DOI: 10.1038/s41413-025-00440-1

Jialiang S Wang,Katelyn Strauss,Caroline Houghton,Numa Islam,Sung-Hee Yoon,Tatsuya Kobayashi,Daniel J Brooks,Mary L Bouxsein,Yingshe Zhao,Cristal S Yee,Tamara N Alliston,Marc N Wein

{"title":"Osteoclast-independent osteocyte dendrite defects in mice bearing the osteogenesis imperfecta-causing Sp7 R342C mutation.","authors":"Jialiang S Wang,Katelyn Strauss,Caroline Houghton,Numa Islam,Sung-Hee Yoon,Tatsuya Kobayashi,Daniel J Brooks,Mary L Bouxsein,Yingshe Zhao,Cristal S Yee,Tamara N Alliston,Marc N Wein","doi":"10.1038/s41413-025-00440-1","DOIUrl":"https://doi.org/10.1038/s41413-025-00440-1","url":null,"abstract":"Osteogenesis imperfecta (OI) is a group of diseases caused by defects in type I collagen processing which result in skeletal fragility. While these disorders have been regarded as defects in osteoblast function, the role of matrix-embedded osteocytes in OI pathogenesis remains largely unknown. Homozygous human SP7 (c.946 C > T, R316C) mutation results in a recessive form of OI characterized by fragility fractures, low bone mineral density and osteocyte dendrite defects. To better understand how the OI-causing R316C mutation affects the function of SP7, we generated Sp7R342C knock-in mice. Consistent with patient phenotypes, Sp7R342C/R342C mice demonstrate increased cortical porosity and reduced cortical bone mineral density. Sp7R342C/R342C mice show osteocyte dendrite defects, increased osteocyte apoptosis, and intracortical bone remodeling with ectopic intracortical osteoclasts and elevated osteocyte Tnfsf11 expression. Remarkably, these defects in osteocyte function contrast to only mild changes in mature osteoblast function, suggesting that this Sp7 mutation selectively interferes with the function of Sp7 in osteocytes and mature osteoblasts, but not during early stages of osteoblast differentiation. Osteocyte morphology changes in Sp7R342C/R342C mice were not restored by inhibiting osteoclast formation, indicating that dendrite defects lie upstream of high intracortical osteoclast activity in this model. Moreover, transcriptomic profiling reveals that the expression of a core set osteocyte-enriched genes is highly dysregulated by the R342C mutation. Thus, this supports a model in which osteocyte dysfunction can drive OI pathogenesis and provides a valuable resource to test novel therapeutic approaches and to understand the osteocyte-specific role of SP7 in bone remodeling.","PeriodicalId":9134,"journal":{"name":"Bone Research","volume":"5 1","pages":"70"},"PeriodicalIF":12.7,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144664280","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

Cellular senescence and other age-related mechanisms in skeletal diseases 骨骼疾病中的细胞衰老和其他与年龄相关的机制

IF 12.7 1区医学

Bone Research Pub Date : 2025-07-07 DOI: 10.1038/s41413-025-00448-7

Ke Li, Sihan Hu, Hao Chen

引用次数: 0

Single-cell transcriptomic analysis identifies systemic immunosuppressive myeloid cells and local monocytes/macrophages as key regulators in polytrauma-induced immune dysregulation 单细胞转录组学分析发现全身免疫抑制的骨髓细胞和局部单核/巨噬细胞是多重创伤诱导的免疫失调的关键调节因子

IF 12.7 1区医学

Bone Research Pub Date : 2025-07-07 DOI: 10.1038/s41413-025-00444-x

Drishti Maniar, M. Cole Keenum, Casey E. Vantucci, Tyler Guyer, Paramita Chatterjee, Kelly Leguineche, Kaitlyn Cheung, Robert E. Guldberg, Krishnendu Roy

{"title":"Single-cell transcriptomic analysis identifies systemic immunosuppressive myeloid cells and local monocytes/macrophages as key regulators in polytrauma-induced immune dysregulation","authors":"Drishti Maniar, M. Cole Keenum, Casey E. Vantucci, Tyler Guyer, Paramita Chatterjee, Kelly Leguineche, Kaitlyn Cheung, Robert E. Guldberg, Krishnendu Roy","doi":"10.1038/s41413-025-00444-x","DOIUrl":"https://doi.org/10.1038/s41413-025-00444-x","url":null,"abstract":"Polytrauma with significant bone and volumetric muscle loss presents substantial clinical challenges. Although immune responses significantly influence fracture healing post-polytrauma, the cellular and molecular underpinnings of polytrauma-induced immune dysregulation require further investigation. While previous studies examined either injury site tissue or systemic tissue (peripheral blood), our study uniquely investigated both systemic and local immune cells at the same time to better understand polytrauma-induced immune dysregulation and associated impaired bone healing. Using single-cell RNA sequencing (scRNA-seq) in a rat polytrauma model, we analyzed blood, bone marrow, and the local defect soft tissue to identify potential cellular and molecular targets involved in immune dysregulation. We identified a trauma-associated immunosuppressive myeloid (TIM) cell population that drives systemic immune dysregulation, immunosuppression, and potentially impaired bone healing. We found CD1d as a global marker for TIM cells in polytrauma. In the local defect tissue, we observed Spp1+ monocytes/macrophages mediating inflammatory, fibrotic, and impaired adaptive immune responses. Finally, our findings highlighted increased signaling via Anxa1-Fpr2 and Spp1-Cd44 axes. This comprehensive analysis enhances our understanding of immune dysregulation-mediated nonunion following traumatic injury and provides biomarkers that could function as treatment targets.","PeriodicalId":9134,"journal":{"name":"Bone Research","volume":"111 1","pages":""},"PeriodicalIF":12.7,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144568325","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