Journal of Orthopaedic Translation最新文献

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Near-infrared smart responsive orthopedic implants with synergistic antimicrobial and bone integration-promoting properties 具有协同抗菌和促进骨整合特性的近红外智能响应骨科植入物
IF 5.9 1区 医学
Journal of Orthopaedic Translation Pub Date : 2025-04-09 DOI: 10.1016/j.jot.2025.03.015
Ziming Liao , Luyao Zhang , Jingxuan Li , Yujie Zhou , Yu Cao , Yan Wei , Jingjing Du , Li Lu , Di Huang
{"title":"Near-infrared smart responsive orthopedic implants with synergistic antimicrobial and bone integration-promoting properties","authors":"Ziming Liao ,&nbsp;Luyao Zhang ,&nbsp;Jingxuan Li ,&nbsp;Yujie Zhou ,&nbsp;Yu Cao ,&nbsp;Yan Wei ,&nbsp;Jingjing Du ,&nbsp;Li Lu ,&nbsp;Di Huang","doi":"10.1016/j.jot.2025.03.015","DOIUrl":"10.1016/j.jot.2025.03.015","url":null,"abstract":"<div><h3>Background</h3><div>The decline in antibiotic use has made the treatment of post-implant infections increasingly challenging, especially the problem of bacterial invasion caused by inadequate tissue fusion with the implant in the early stages of the implant. Developing multiple methods to reduce bacterial infections through synergies will be superior to a single model of antimicrobial means.</div></div><div><h3>Methods</h3><div>The composite coating composed of titanium phosphate (TiP)/copper oxide nanoparticles (CuO)/nano-hydroxyapatite (n-HA) named TiP-ua was used to kill <em>Staphylococcus aureus</em> (<em>S. aureus</em>) and <em>Escherichia coli</em> (<em>E. coli</em>) under near infrared (NIR) irradiation by means of photothermal therapy (PTT) and photodynamic therapy (PDT) synergism.</div></div><div><h3>Results</h3><div>The TiP-ua composite coating can reach about 60 °C and produce a certain amount of reactive oxygen species after 15 min irradiation with 980 nm near infrared light with 0.9 W/cm<sup>2</sup> power. Under the NIR irradiation of 0.9 W/cm<sup>2</sup> power for 10 min, the composite coating can achieve about 90% killing effect on <em>S. aureus</em> and more than 90% killing effect on <em>E. coli</em>. In terms of mouse pre-osteoblasts (MC3T3-E1), TiP-ua showed more superiority in promoting osteogenic differentiation ability. In the mouse infection model, it also showed good antibacterial effect, and could significantly reduce the expression of inflammatory factors and accelerate wound healing. In the bone defect model, the intervention significantly accelerated the regeneration of neobone tissue and enhanced osseointegration capacity.</div></div><div><h3>Conclusions</h3><div>The experimental results show that TiP-ua coating not only has good photothermal conversion ability, but also has good biosafety, which can accelerate the regeneration and repair of bone tissue around the implant, including accelerating the osteogenic differentiation of cells, and reduce the activity of bacteria to effectively reduce the inflammatory response.</div></div><div><h3>The translational potential of this article</h3><div>The collaborative antibacterial and bone repair coating in this study has a simple preparation process, high repeatability, high biosafety and positive effect on bone tissue repair, and has great clinical application potential in orthopedics and dental implants.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"52 ","pages":"Pages 55-69"},"PeriodicalIF":5.9,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143799355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Chronic motoneuronal activation enhanced axonal regeneration and functional recovery after brachial plexus injury 慢性运动神经元激活促进臂丛神经损伤后轴突再生和功能恢复
IF 5.9 1区 医学
Journal of Orthopaedic Translation Pub Date : 2025-04-02 DOI: 10.1016/j.jot.2025.02.007
Shiqin Lv , Zizhuo Wu , Yu Huang , Pingzhen Wu , Jianqing Shao , Jiajia Wu , Ke Zhong , Lihua Zhou , Wutian Wu
{"title":"Chronic motoneuronal activation enhanced axonal regeneration and functional recovery after brachial plexus injury","authors":"Shiqin Lv ,&nbsp;Zizhuo Wu ,&nbsp;Yu Huang ,&nbsp;Pingzhen Wu ,&nbsp;Jianqing Shao ,&nbsp;Jiajia Wu ,&nbsp;Ke Zhong ,&nbsp;Lihua Zhou ,&nbsp;Wutian Wu","doi":"10.1016/j.jot.2025.02.007","DOIUrl":"10.1016/j.jot.2025.02.007","url":null,"abstract":"<div><h3>Background</h3><div>Brachial plexus injury (BPI) leads to significant impairment of upper limb motor function, primarily due to progressive atrophy of denervated muscles resulting from the slow rate of axonal regeneration. Therefore, identifying strategies to accelerate axon extension is of critical importance.</div></div><div><h3>Methods</h3><div>In this study, we first established a mouse model of brachial plexus injury and employed chemogenetic approaches to specifically activate C6 spinal motoneurons. We then assessed axonal regeneration and motor function recovery in the injured mice through behavioral tests, morphological analyses, and electrophysiological detection.</div></div><div><h3>Results</h3><div>We found that the AAV9-hM3Dq virus efficiently transduced motoneurons, and CNO administration robustly activated mature hM3Dq<sup>+</sup> motoneurons in vivo. Chronic chemogenetic activation significantly enhanced the regeneration of spinal motoneurons injured by ventral root crush, accelerated axon extension, and improved axonal remyelination, resulting in increased axon size. This activation also facilitated the formation of new neuromuscular junctions (NMJs) in adult motoneurons and reduced muscle atrophy. Furthermore, it promoted electrophysiological recovery of the motor unit and improved overall motor function.</div></div><div><h3>Conclusion</h3><div>Chemogenetic activation of adult motoneurons can robustly enhances axon growth and mediate better behavioral recovery. These findings highlight the therapeutic potential of chemogenetic neuronal activation in promoting functional recovery following nerve injury.</div></div><div><h3>The translational potential of this article</h3><div>We have established a chronic chemogenetic method to activate hM3Dq<sup>+</sup> motor neurons after brachial plexus injury, which accelerates axonal regeneration and enhances functional recovery. This strategy holds promise as a clinical therapeutic approach for treating nervous system injuries.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"52 ","pages":"Pages 40-54"},"PeriodicalIF":5.9,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143759043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
RO5126766 attenuates osteoarthritis by inhibiting osteoclastogenesis and protecting chondrocytes through mediating the ERK pathway RO5126766通过介导ERK通路抑制破骨细胞发生,保护软骨细胞,从而减轻骨关节炎
IF 5.9 1区 医学
Journal of Orthopaedic Translation Pub Date : 2025-03-27 DOI: 10.1016/j.jot.2025.03.002
Han Wang , Xiwen Yuan , Jie Han , Zuoxing Wu , Zheru Ma , Fan Shi , Zhengqiong Luo , Zihan Chen , Chenyang Guo , Guixin Yuan , Xuemei He , Zemin Ling , Lin Meng , Rong Shen , Jianming Huang , Ren Xu
{"title":"RO5126766 attenuates osteoarthritis by inhibiting osteoclastogenesis and protecting chondrocytes through mediating the ERK pathway","authors":"Han Wang ,&nbsp;Xiwen Yuan ,&nbsp;Jie Han ,&nbsp;Zuoxing Wu ,&nbsp;Zheru Ma ,&nbsp;Fan Shi ,&nbsp;Zhengqiong Luo ,&nbsp;Zihan Chen ,&nbsp;Chenyang Guo ,&nbsp;Guixin Yuan ,&nbsp;Xuemei He ,&nbsp;Zemin Ling ,&nbsp;Lin Meng ,&nbsp;Rong Shen ,&nbsp;Jianming Huang ,&nbsp;Ren Xu","doi":"10.1016/j.jot.2025.03.002","DOIUrl":"10.1016/j.jot.2025.03.002","url":null,"abstract":"<div><h3>Background</h3><div>Osteoarthritis (OA) is a degenerative joint disease that remains challenging to treat due to lack of complete understanding of its pathogenesis. Previous studies have identified RO5126766 (RO) as a small molecule compound that inhibited RAF/MEK-ERK pathway and garnered much interest for its anti-cancer properties. But its role in the treatment of OA remains unclear.</div></div><div><h3>Methods</h3><div>This study employed the anterior cruciate ligament transection (ACLT) procedure to create an OA model in mice. The effects of RO on pathological changes in articular cartilage and subchondral bone were assessed using micro-CT and histological staining. Mice received peritoneal injections of RO at 1 mg/kg and 5 mg/kg biweekly for 4 weeks after ACLT, while control mice received saline. <em>In vitro</em>, bone marrow-derived macrophages were cultured to examine the effects of RO on osteoclast activation using immunofluorescence, TRAP staining, and bone resorption assays. The inflammatory degeneration of chondrocytes and gene expression levels were evaluated using staining and RT-qPCR. Western blot and immunohistochemistry were used to analyze MAPK signaling and autophagy-related protein expression, investigating RO's molecular mechanism in OA treatment. Human single-cell data were also analyzed to identify genes and pathways upregulated in OA tissues.</div></div><div><h3>Results</h3><div>Our findings showed that RO protects subchondral bone by inhibiting osteoclast formation in the ACLT mouse model of OA. <em>In vitro</em>, RO was shown to inhibit osteoclast differentiation and reduce inflammatory degeneration of chondrocytes. Mechanistically, RO counteracted subchondral osteoclast hyperactivation by suppressing the ERK/c-fos/NFATc1 signaling pathway. Additionally, RO inhibited LPS-induced inflammatory degeneration of chondrocytes and enhanced autophagy via the ERK pathway. Single-cell analysis further confirmed significant upregulation of the ERK signaling pathway in human OA tissues.</div></div><div><h3>Conclusions</h3><div>Overall, our findings suggested that RO inhibited osteoclast differentiation and protected articular cartilage, suggesting its potential as a novel treatment for OA.</div></div><div><h3>Translational potential of this article</h3><div>In this study, we have, for the first time, substantiated the therapeutic potential of RO in the treatment of OA. By demonstrating its ability to inhibit osteoclast differentiation and protect articular cartilage, RO could offer a new avenue for disease-modifying treatments in OA. Thus, this paper provides valuable insights into understanding the molecular mechanisms and treatment of OA.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"52 ","pages":"Pages 27-39"},"PeriodicalIF":5.9,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143715563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The effects and mechanisms of electromagnetic fields on bone remodeling: From clinical to laboratory 电磁场对骨重塑的影响及其机制:从临床到实验室
IF 5.9 1区 医学
Journal of Orthopaedic Translation Pub Date : 2025-03-24 DOI: 10.1016/j.jot.2025.03.003
Junyu Liu , Weihao Ren , Shenghang Wang , Jiancheng Yang , Hao Zhang , Yuhong Zeng , Dachuan Yin , Peng Shang
{"title":"The effects and mechanisms of electromagnetic fields on bone remodeling: From clinical to laboratory","authors":"Junyu Liu ,&nbsp;Weihao Ren ,&nbsp;Shenghang Wang ,&nbsp;Jiancheng Yang ,&nbsp;Hao Zhang ,&nbsp;Yuhong Zeng ,&nbsp;Dachuan Yin ,&nbsp;Peng Shang","doi":"10.1016/j.jot.2025.03.003","DOIUrl":"10.1016/j.jot.2025.03.003","url":null,"abstract":"<div><div>Electromagnetic fields (EMFs) are physical fields generated by electrically charged objects, and play a vital role in the growth and development of living organisms. Bone is a highly dynamic structure that undergoes a constant remodeling process. From 1962 to 1977, Bassett discovered the piezoelectric effect in bone tissue and found that EMFs accelerated osteogenesis, promoted tibial fracture healing in dogs, and had positive effects in clinical trials. Since then, EMFs have been increasingly studied in bone remodeling disorders as a non-invasive physical therapy. This review summarizes clinical trials and laboratory studies on EMF interventions in bone remodeling disorders over the past few decades, outlining the effects of EMFs on various bone cells and their underlying molecular mechanisms. In addition, we propose issues in current studies and give an outlook on the research and application of EMFs as a non-invasive physical therapy.</div></div><div><h3>The translational potential of this article</h3><div>This article systematically reviews the research ranging from biological and physical mechanisms to medical applications of EMFs on bone remodeling and related diseases, identifies key challenges in future basic research, and proposes new strategies for developing novel medical equipment and advancing clinical applications in this field. These insights contribute to the advancement of non-invasive physical therapies in orthopedics.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"52 ","pages":"Pages 14-26"},"PeriodicalIF":5.9,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143683121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Single-cell transcriptomic analysis reveals AP-1 downregulation remodels bone marrow environment and contributes to osteopenia in ovariectomized mice 单细胞转录组学分析显示AP-1下调重塑骨髓环境并导致去卵巢小鼠骨质减少
IF 5.9 1区 医学
Journal of Orthopaedic Translation Pub Date : 2025-03-21 DOI: 10.1016/j.jot.2025.03.001
Zhanrong Zhang , Zhengbo Tao , Zheng Zhang , Weijin Zhang , Xuanrui Zhang , Xunpei Xu , Rui Gao , Xia Tao , Xuhui Zhou
{"title":"Single-cell transcriptomic analysis reveals AP-1 downregulation remodels bone marrow environment and contributes to osteopenia in ovariectomized mice","authors":"Zhanrong Zhang ,&nbsp;Zhengbo Tao ,&nbsp;Zheng Zhang ,&nbsp;Weijin Zhang ,&nbsp;Xuanrui Zhang ,&nbsp;Xunpei Xu ,&nbsp;Rui Gao ,&nbsp;Xia Tao ,&nbsp;Xuhui Zhou","doi":"10.1016/j.jot.2025.03.001","DOIUrl":"10.1016/j.jot.2025.03.001","url":null,"abstract":"<div><h3>Background</h3><div>Estrogen deficiency-induced osteoporosis largely results from disrupted immune environment in bone marrow, yet the underlying cellular and molecular mechanisms remain incompletely understood. This study aimed to investigate how estrogen deficiency alters bone marrow cellular composition and signaling pathways, with a focus on the regulatory role of activator protein 1 (AP-1) and its impact on osteoclastogenesis.</div></div><div><h3>Methods</h3><div>Single-cell RNA sequencing (scRNA-seq) was performed on bone marrow cells from sham-operated and ovariectomized (OVX) mice to map cell-type-specific changes. AP-1 inhibitor T5224 was administered to validate its functional role in vivo, while in vitro experiments assessed AP-1 activation via estrogen receptor signaling under estrogen stimulation. B lymphogenesis was pharmacologically inhibited using an IL-7 monoclonal antibody in OVX mice to evaluate its therapeutic potential.</div></div><div><h3>Results</h3><div>OVX mice exhibited a marked expansion of proliferative B cells (enriched in protein translation/DNA replication pathways) and reduced neutrophil proportions. scRNA-seq revealed widespread downregulation of AP-1 subunits, namely Fos, Fosb, Jun, Junb, across multiple cell types. T5224-induced AP-1 inhibition recapitulated OVX-associated B cell/neutrophil imbalance and triggered significant bone loss. Mechanistically, estrogen receptor activation upregulated AP-1 under estrogen stimulation, whereas AP-1 inhibition promoted B cell proliferation and increased GM-CSF and RANKL levels, thereby facilitating osteoclastogenesis. Critically, IL-7 antibody-mediated suppression of B lymphogenesis in OVX mice substantially attenuated bone loss.</div></div><div><h3>Conclusion</h3><div>AP-1 downregulation drives estrogen deficiency-related osteopenia by disrupting bone marrow homeostasis, primarily through excessive B cell expansion and elevated osteoclastogenic signaling. Targeting B cell proliferation via IL-7 blockade presents a potential therapeutic strategy for mitigating osteoporosis in estrogen-deficient conditions.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"52 ","pages":"Pages 1-13"},"PeriodicalIF":5.9,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143683123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Exploring molecular and cellular signaling pathways: Unraveling the pathogenesis of tendinopathy 探索分子和细胞信号通路:揭示肌腱病变的发病机制
IF 5.9 1区 医学
Journal of Orthopaedic Translation Pub Date : 2025-03-01 DOI: 10.1016/j.jot.2025.02.003
Zihan Xu , Wenjing Hou , Tao Zhang , Rui Chen , Thomas Skutella
{"title":"Exploring molecular and cellular signaling pathways: Unraveling the pathogenesis of tendinopathy","authors":"Zihan Xu ,&nbsp;Wenjing Hou ,&nbsp;Tao Zhang ,&nbsp;Rui Chen ,&nbsp;Thomas Skutella","doi":"10.1016/j.jot.2025.02.003","DOIUrl":"10.1016/j.jot.2025.02.003","url":null,"abstract":"<div><div>Despite the long healing duration of tendon injuries, the outcomes of repairs are frequently suboptimal, resulting in persistent pain and reduced functionality. Current clinical approaches to tendinopathy are primarily symptomatic, encompassing nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroid injections, physical therapies, surgical interventions, loading programs, and pain management. Yet, these treatments have protracted timelines and their efficacy remains uncertain. This uncertainty stems largely from an incomplete understanding of tendinopathy's pathogenesis. Unraveling the mechanisms behind tendinopathy is essential for devising novel therapeutic strategies. In this context, this review systematic reviewed more recent cellular and molecular literature in tendinopathy, in order to summarize the up-to-date advancements including the structure and composition of healthy tendons, the pathophysiological changes in tendinopathy, the molecular pathways implicated in various forms of the condition, and current effective treatment methods. This review not only aims to offer insights but also to inspire further investigation into the mechanisms and clinical management of tendinopathy.</div></div><div><h3>The translational potential of this article</h3><div>A deficient understanding of the molecular mechanisms hampers the advancement of therapeutic strategies and drug development. Consequently, an in-depth examination of these molecular mechanisms is essential for comprehending the etiology of tendinopathy and for devising effective clinical management strategies.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"51 ","pages":"Pages 298-311"},"PeriodicalIF":5.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143682112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
ISRIB facilitates post-spinal cord injury recovery through attenuation of neuronal apoptosis and modulation of neuroinflammation ISRIB通过抑制神经元凋亡和调节神经炎症促进脊髓损伤后的恢复
IF 5.9 1区 医学
Journal of Orthopaedic Translation Pub Date : 2025-03-01 DOI: 10.1016/j.jot.2025.01.003
Qingyang Li , Chi Zhang , Enlin Qi , Mingxin Wu , Haijian Sun , Tao Zhang , Yunpeng Jiang , Hao Li , Ruizhi Jiang , Chuang Li , Hua Zhao , Hengxing Zhou , Shiqing Feng
{"title":"ISRIB facilitates post-spinal cord injury recovery through attenuation of neuronal apoptosis and modulation of neuroinflammation","authors":"Qingyang Li ,&nbsp;Chi Zhang ,&nbsp;Enlin Qi ,&nbsp;Mingxin Wu ,&nbsp;Haijian Sun ,&nbsp;Tao Zhang ,&nbsp;Yunpeng Jiang ,&nbsp;Hao Li ,&nbsp;Ruizhi Jiang ,&nbsp;Chuang Li ,&nbsp;Hua Zhao ,&nbsp;Hengxing Zhou ,&nbsp;Shiqing Feng","doi":"10.1016/j.jot.2025.01.003","DOIUrl":"10.1016/j.jot.2025.01.003","url":null,"abstract":"<div><h3>Background</h3><div>Neuronal apoptosis and inflammation are two critical factors that impede functional recovery post spinal cord injury (SCI). Previous studies have demonstrated the inhibitory effects of integrated stress response inhibitor (ISRIB) on neuroinflammation in brain injury. However, whether ISRIB can regulate neuron death and neuroinflammation in the context of SCI remains elusive.</div></div><div><h3>Methods</h3><div>We employed an oxygen-glucose deprivation/reperfusion (OGD/R) model to simulate spinal cord ischemia-reperfusion injury and utilized lipopolysaccharide (LPS) to activate microglia. We assessed cell viability and death to demonstrate the neuroprotective effect of ISRIB against neuron death, while evaluating cytokine levels and the expression of Arg1 and iNOS to elucidate the regulatory role of ISRIB in neuroinflammation. Bulk RNA-seq analysis was employed to investigate the global transcriptional changes in neurons and microglia induced by ISRIB treatment. Additionally, we validated the promoting effects of ISRIB on motor and sensory recovery in a mouse model of SCI.</div></div><div><h3>Results</h3><div>We observed that ISRIB exerted a suppressive effect on neuron death and neuroinflammation. RNA-seq data revealed that the ISRIB exhibited regulation of neuron apoptosis through the P53 signaling pathway, as well as modulation of neuroinflammation by the JAK2/STAT3 signaling pathway. Western blotting and immunofluorescence analyses demonstrated that ISRIB reduced P53 expression in neuronal nuclei and inhibited the phosphorylation of JAK2 and STAT3 in microglia. In addition, we validated the capacity of ISRIB to promote locomotor function recovery in a mouse model of SCI.</div></div><div><h3>Conclusion</h3><div>Our study confirmed the ability of ISRIB to regulate neuron apoptosis and neuroinflammation in SCI via the P53 signaling pathway and the JAK2/STAT3 signaling pathway, respectively. Treatment with ISRIB in mice with SCI promoted the recovery of neural function. This research provides new evidence and options for therapeutic strategies of SCI.</div></div><div><h3>The translational potential of this article</h3><div>Our study provides experimental evidence to support the application of ISRIB in the repair of spinal cord injury.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"51 ","pages":"Pages 119-131"},"PeriodicalIF":5.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143562612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Targeting Piezo1 channel to alleviate intervertebral disc degeneration 靶向Piezo1通道缓解椎间盘退变
IF 5.9 1区 医学
Journal of Orthopaedic Translation Pub Date : 2025-03-01 DOI: 10.1016/j.jot.2025.01.006
Feiyun Li , Mingjue Chen , Mengrui Zhang , Sheng Chen , Minghao Qu , Shuangshuang He , Lin Wang , Xiaohao Wu , Guozhi Xiao
{"title":"Targeting Piezo1 channel to alleviate intervertebral disc degeneration","authors":"Feiyun Li ,&nbsp;Mingjue Chen ,&nbsp;Mengrui Zhang ,&nbsp;Sheng Chen ,&nbsp;Minghao Qu ,&nbsp;Shuangshuang He ,&nbsp;Lin Wang ,&nbsp;Xiaohao Wu ,&nbsp;Guozhi Xiao","doi":"10.1016/j.jot.2025.01.006","DOIUrl":"10.1016/j.jot.2025.01.006","url":null,"abstract":"<div><h3>Background</h3><div>Low back pain impacts over 600 million people worldwide, predominantly due to intervertebral disc degeneration. This study focuses on the role of Piezo1, a crucial mechanosensitive ion channel protein, in the pathology and potential treatment of disc degeneration.</div></div><div><h3>Materials and methods</h3><div>To investigate the effects of disc-specific Piezo1 deletion, we generated <em>Aggrecan</em><sup><em>CreERT2</em></sup><em>; Piezo1</em><sup><em>fl/fl</em></sup> mice and examined both lumbar spine instability (LSI)- and aging-induced disc degeneration. Additionally, the effect of pharmacological inhibition of Piezo1 was evaluated using GsMTx4, a potent Piezo1 antagonist, in an ex vivo model stimulated with IL-1β to induce disc degeneration. Assessments included histological examinations, immunofluorescence, and western blot analyses to thoroughly characterize the alterations in the intervertebral discs.</div></div><div><h3>Results</h3><div>Elevated expression of Piezo1 was detected in the nucleus pulposus (NP) of intervertebral discs with advanced disc degeneration in both aged mice and human patients. Inducible deletion of Piezo1 expression in aggrecan-expressing disc cells significantly reduced lumbar disc degeneration, decreased extracellular matrix (ECM) degradation, and lowered apoptosis in NP cells, observed in both aged mice and those undergoing LSI surgery. Excessive compression loading (CL) upregulated Piezo1 expression, induced ECM disruption, and increased apoptosis in NP cells, whereas inhibition of Piezo1 with GsMTx4 effectively mitigated these pathological changes. Furthermore, in ex vivo cultured mouse discs, GsMTx4 treatment significantly alleviated IL-1β-induced degenerative damages, restored ECM anabolism, and reduced apoptosis.</div></div><div><h3>Conclusions</h3><div>The findings suggest that Piezo1 plays a critical role in the development of disc degeneration and highlight its potential as a therapeutic target. Inhibiting Piezo1 could offer a novel strategy for treating or preventing this critical disease.</div></div><div><h3>Translational potential of this article</h3><div>This research highlights the involvement of Piezo1 in the development of intervertebral disc degeneration and emphasizes the potential for targeting Piezo1 as a therapeutic strategy to delay or reverse this condition.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"51 ","pages":"Pages 145-158"},"PeriodicalIF":5.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143578971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Corrigendum to ‘Memantine attenuates the development of osteoarthritis by blocking NMDA receptor mediated calcium overload and chondrocyte senescence’ [2024 Aug 27:48:204-216] 美金刚通过阻断NMDA受体介导的钙超载和软骨细胞衰老来减轻骨关节炎的发展[2024 Aug 27:48:204-216]
IF 5.9 1区 医学
Journal of Orthopaedic Translation Pub Date : 2025-03-01 DOI: 10.1016/j.jot.2025.02.005
Qingmei Cheng , Ke He , Junyu Zhu , Xiaoxiao Li , Xuan Wu , Chao Zeng , Guanghua Lei , Ning Wang , Hui Li , Jie Wei
{"title":"Corrigendum to ‘Memantine attenuates the development of osteoarthritis by blocking NMDA receptor mediated calcium overload and chondrocyte senescence’ [2024 Aug 27:48:204-216]","authors":"Qingmei Cheng ,&nbsp;Ke He ,&nbsp;Junyu Zhu ,&nbsp;Xiaoxiao Li ,&nbsp;Xuan Wu ,&nbsp;Chao Zeng ,&nbsp;Guanghua Lei ,&nbsp;Ning Wang ,&nbsp;Hui Li ,&nbsp;Jie Wei","doi":"10.1016/j.jot.2025.02.005","DOIUrl":"10.1016/j.jot.2025.02.005","url":null,"abstract":"","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"51 ","pages":"Page 176"},"PeriodicalIF":5.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143620634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Integration of longitudinal load-bearing tissue MRI radiomics and neural network to predict knee osteoarthritis incidence 纵向承重组织MRI放射组学与神经网络的结合预测膝关节骨关节炎的发病率
IF 5.9 1区 医学
Journal of Orthopaedic Translation Pub Date : 2025-03-01 DOI: 10.1016/j.jot.2025.01.007
Tianyu Chen , Jian Chen , Hao Liu , Zhengrui Liu , Bin Yu , Yang Wang , Wenbo Zhao , Yinxiao Peng , Jun Li , Yun Yang , Hang Wan , Xing Wang , Zhong Zhang , Deng Zhao , Lan Chen , Lili Chen , Ruyu Liao , Shanhong Liu , Guowei Zeng , Zhijia Wen , Yingze Zhang
{"title":"Integration of longitudinal load-bearing tissue MRI radiomics and neural network to predict knee osteoarthritis incidence","authors":"Tianyu Chen ,&nbsp;Jian Chen ,&nbsp;Hao Liu ,&nbsp;Zhengrui Liu ,&nbsp;Bin Yu ,&nbsp;Yang Wang ,&nbsp;Wenbo Zhao ,&nbsp;Yinxiao Peng ,&nbsp;Jun Li ,&nbsp;Yun Yang ,&nbsp;Hang Wan ,&nbsp;Xing Wang ,&nbsp;Zhong Zhang ,&nbsp;Deng Zhao ,&nbsp;Lan Chen ,&nbsp;Lili Chen ,&nbsp;Ruyu Liao ,&nbsp;Shanhong Liu ,&nbsp;Guowei Zeng ,&nbsp;Zhijia Wen ,&nbsp;Yingze Zhang","doi":"10.1016/j.jot.2025.01.007","DOIUrl":"10.1016/j.jot.2025.01.007","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Load-bearing structural degradation is crucial in knee osteoarthritis (KOA) progression, yet limited prediction models use load-bearing tissue radiomics for radiographic (structural) KOA incident.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Purpose&lt;/h3&gt;&lt;div&gt;We aim to develop and test a Load-Bearing Tissue plus Clinical variable Radiomic Model (LBTC-RM) to predict radiographic KOA incidents.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Study design&lt;/h3&gt;&lt;div&gt;Risk prediction study.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;The 700 knees without radiographic KOA at baseline were included from Osteoarthritis Initiative cohort. We selected 2164 knee MRIs during 4-year follow-up. LBTC-RM, which integrated MRI features of meniscus, femur, tibia, femorotibial cartilage, and clinical variables, was developed in total development cohort (n = 1082, 542 cases vs. 540 controls) using neural network algorithm. Final predictive model was tested in total test cohort (n = 1082, 534 cases vs. 548 controls), which integrated data from five visits: baseline (n = 353, 191 cases vs. 162 controls), 3 years prior KOA (n = 46, 19 cases vs. 27 controls), 2 years prior KOA (n = 143, 77 cases vs. 66 controls), 1 year prior KOA (n = 220, 105 cases vs. 115 controls), and at KOA incident (n = 320, 156 cases vs. 164 controls).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;In total test cohort, LBTC-RM predicted KOA incident with AUC (95 % CI) of 0.85 (0.82–0.87); with LBTC-RM aid, performance of resident physicians for KOA prediction were improved, with specificity, sensitivity, and accuracy increasing from 50 %, 60 %, and 55 %–72 %, 73 %, and 72 %, respectively. The LBTC-RM output indicated an increased KOA risk (OR: 20.6, 95 % CI: 13.8–30.6, p &lt; .001). Radiomic scores of load-bearing tissue raised KOA risk (ORs: 1.02–1.9) from 4-year prior KOA whereas 3-dimensional feature score of medial meniscus decreased the OR (0.99) of KOA incident at KOA confirmed. The 2-dimensional feature score of medial meniscus increased the ORs (1.1–1.2) of KOA symptom score from 2-year prior KOA.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;We provided radiomic features of load-bearing tissue to improved KOA risk level assessment and incident prediction. The model has potential clinical applicability in predicting KOA incidents early, enabling physicians to identify high-risk patients before significant radiographic evidence appears. This can facilitate timely interventions and personalized management strategies, improving patient outcomes.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;The Translational Potential of this Article&lt;/h3&gt;&lt;div&gt;This study presents a novel approach integrating longitudinal MRI-based radiomics and clinical variables to predict knee osteoarthritis (KOA) incidence using machine learning. By leveraging deep learning for auto-segmentation and machine learning for predictive modeling, this research provides a more interpretable and clinically applicable method for early KOA detection. The introduction of a Radiomics Score System enhances ","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"51 ","pages":"Pages 187-197"},"PeriodicalIF":5.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143628459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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