Journal of Orthopaedic Translation最新文献

{"title":"Guideline for adolescent scoliosis screening in China (public version 2024)","authors":"Chinese Orthopedic Association,&nbsp;Yu Zhao ,&nbsp;Yan Zhao ,&nbsp;Sheng Lu ,&nbsp;Qiang Yang ,&nbsp;Liang Chen ,&nbsp;Xinlong Ma ,&nbsp;Guixing Qiu","doi":"10.1016/j.jot.2024.09.006","DOIUrl":"10.1016/j.jot.2024.09.006","url":null,"abstract":"<div><h3>Background</h3><div>Scoliosis screening policies vary around the world depending on the situation. In China, based on the high prevalence and low consultation rate of scoliosis, the Clinical Practice Guidelines and Pathway Guidelines for Scoliosis Screening in Chinese Adolescents were released in 2021 to provide clinical guidance for the screening of this condition. However, public awareness of scoliosis screening is currently very low, and raising awareness among parents and teachers and promoting home-based screening are important tools to improve diagnosis rates.</div></div><div><h3>Method</h3><div>The guideline development group collected over 1000 questionnaires to identify the issues addressed in the guideline and invited 75 Chinese spine surgery experts to use the Delphi method to form the recommendations, ultimately resulting in the formation of this guideline. They proposed 11 recommendations addressing 9 issues, providing methods for both home screening and school screening.</div></div><div><h3>Result</h3><div>The guideline presents recommendations on the reasons for scoliosis screening, the target population, screening methods, post-screening diagnosis, and referrals. It also proposes standardized methods for home screening and school screening. Home screening method for scoliosis include back and spine shape observation and forward bending test. School screening methods for scoliosis include visual inspection, the forward bending test, portable scoliosis screening tools, scoliosis ultrasound screening tools and so on.</div></div><div><h3>Conclusion</h3><div>The guideline can provide easy-to-understand knowledge on scoliosis screening in adolescents, thereby improving the diagnosis rate of the disease and promoting early treatment. Early intervention and management of scoliosis is expected to reduce the potential risks associated with scoliosis in adolescents in the future.</div></div><div><h3>The Translational Potential of this Article</h3><div>This article can promote the application of various scoliosis screening methods in future scoliosis screenings (including portable scoliosis screening tools), extend Chinese perspectives on scoliosis screening to the global stage, advance the translation of research achievements in the field of scoliosis screening, enhance the diagnosis rate of early scoliosis, and reduce the incidence of severe adolescent scoliosis.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"50 ","pages":"Pages 364-372"},"PeriodicalIF":5.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143600681","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}

{"title":"The Vitamin D-Sirt1/PGC1α Axis Regulates Bone Metabolism and Counteracts Osteoporosis","authors":"Cuicui Yang ,&nbsp;Lulu Chen ,&nbsp;Xiaoli Guo ,&nbsp;Haijian Sun ,&nbsp;Dengshun Miao","doi":"10.1016/j.jot.2024.10.011","DOIUrl":"10.1016/j.jot.2024.10.011","url":null,"abstract":"<div><h3>Background</h3><div>Objective: Vitamin D insufficiency is a major contributor to osteoporosis. This study aimed to elucidate the mechanisms by which the vitamin D-Sirt1/PGC1α axis regulates bone metabolism and counteracts osteoporosis induced by active vitamin D insufficiency.</div></div><div><h3>Methods</h3><div>Mouse models including Sirt1 transgenic (Sirt1^Tg), Cyp27b1^+/− (active vitamin D deficient), and compound Sirt1^TgCyp27b1^+/− mice were utilized. Bone parameters were assessed by radiography, micro-CT, histology, and immunohistochemistry. In vitro studies used bone marrow-derived mesenchymal stem cells (BM-MSCs). Gene and protein expression were analyzed by RT-PCR and Western blotting. Chromatin immunoprecipitation and luciferase assays investigated transcriptional regulation. Effects of resveratrol supplementation were examined.</div></div><div><h3>Results</h3><div>1,25-dihydroxyvitamin D (1,25(OH)₂D) insufficiency caused downregulation of Sirt1 expression, leading to accelerated bone loss. Overexpression of Sirt1 in mesenchymal stem cells corrected bone loss by inhibiting oxidative stress, DNA damage, osteocyte senescence and senescence-associated secretory phenotype, promoting osteoblastic bone formation, and reducing osteoclastic bone resorption. 1,25(OH)₂D₃ transcriptionally upregulated Sirt1 expression in BM-MSCs through vitamin D receptor binding to the Sirt1 gene promoter. Resveratrol, a Sirt1 agonist, attenuated osteoporosis induced by 1,25(OH)₂D insufficiency by modulating the Sirt1/PGC1α axis. Sirt1 interacted with and deacetylated PGC1α, a transcriptional coactivator involved in mitochondrial biogenesis and energy metabolism. Deacetylated PGC1α mediated the effects of Sirt1 on osteogenesis, oxidative stress, and cellular senescence in BM-MSCs.</div></div><div><h3>Conclusion</h3><div>This study elucidated the critical role of the vitamin D-Sirt1/PGC1α axis in regulating bone metabolism and counteracting osteoporosis induced by active vitamin D insufficiency. The findings highlight the potential of this axis as a therapeutic target for the prevention and treatment of osteoporosis.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"50 ","pages":"Pages 211-222"},"PeriodicalIF":5.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11787469/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143079200","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}

{"title":"Risk-stratified lifetime risk and incidence of hip fracture and falls in middle-aged and elderly Chinese population: The China health and retirement longitudinal study","authors":"Guangyuan Du ,&nbsp;Zijuan Fan ,&nbsp;Kenan Fan ,&nbsp;Haifeng Liu ,&nbsp;Jing Zhang ,&nbsp;Dijun Li ,&nbsp;Lei Yan ,&nbsp;Jingwei Jiu ,&nbsp;Ruoqi Li ,&nbsp;Xiaoke Li ,&nbsp;Songyan Li ,&nbsp;Ligan Jia ,&nbsp;Huachen Liu ,&nbsp;Yijia Ren ,&nbsp;Xuanbo Liu ,&nbsp;Jiao Jiao Li ,&nbsp;Bin Wang","doi":"10.1016/j.jot.2024.10.013","DOIUrl":"10.1016/j.jot.2024.10.013","url":null,"abstract":"<div><h3>Background</h3><div>Hip fracture (HF) is one of the most prevalent orthopedic conditions among the elderly, with falls being the primary risk factor for HF. With the surge of aged population, China is facing great challenges from HF and falls. However, a comprehensive long-term observation of risk factors affecting HF and falls and their association are little reported at a national level.</div></div><div><h3>Methods</h3><div>The longitudinal cohort was established using the China Health and Retirement Longitudinal Study (CHARLS) data from 2011 to 2018. The incidence density and multi-risk-stratified lifetime risk (up to 90 years of age) of falls and HF were studied at index ages of 50, 60, and 70, as well as the lifetime risk stratified by six regions in China, based on the modified Kaplan–Meier method with Statistical Analysis System (SAS).</div></div><div><h3>Results</h3><div>This study identified 17 705 subjects aged 50–89. The incidence density of falls was 65.07 and 47.53 per 1000 person-years in women and men, respectively. The incidence density of HF was also higher in women at 5.58 per 1000 person-years than in men at 4.88. By age 50, the lifetime risk of experiencing a HF was 18.58 % for women and 13.72 % for men. Vision and hearing abilities were significantly related to the lifetime risk of both falls and HF. Obesity-related factors presented age-relevant relationships with lifelong risks. Lack of naps, poor lower limb strength, and physical capabilities were indicative of HF risk. The north-western region of China had the lowest lifetime risk of falls but highest risk of HF, while other regions showed a consistent trend between falls and HF.</div></div><div><h3>Conclusion</h3><div>The aging population worldwide faces a considerable risk of falls and HF. Several risk factors were identified in this study using a Chinese population, relating to disease history, lifestyle habits, health status and physical function, and the risks differed among six regions in China. Future precautionary management programs, as well as patient self-awareness are necessary for improving the prevention of falls and HF to reduce their incidence in the aging population.</div></div><div><h3>The translational potential of this article</h3><div>With the greatest aged population worldwide, China faces the unparalleled challenge on public health. The study poses the lifetime risk of hip fracture and falls stratified by multiple risk factors in people from 45 to 90 in a national scale, which would shed a light on the early and continuous prevention of such injury.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"50 ","pages":"Pages 174-184"},"PeriodicalIF":5.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11782876/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080448","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}

{"title":"Harnessing the potential of hyaluronic acid methacrylate (HAMA) hydrogel for clinical applications in orthopaedic diseases","authors":"Junliang Lu ,&nbsp;Zhifei Gao ,&nbsp;Wei He ,&nbsp;Yao Lu","doi":"10.1016/j.jot.2024.11.004","DOIUrl":"10.1016/j.jot.2024.11.004","url":null,"abstract":"<div><div>The treatment of orthopaedic diseases, such as fractures and osteoarthritis, remains a significant challenge due to the complex requirements for mechanical strength and tissue repair. Hydrogels based on hyaluronic acid methacrylate (HAMA) show promise as tissue engineering materials for these conditions. Hyaluronic acid (HA) is a natural component of the extracellular matrix, known for its good compatibility. The mechanical strength of HAMA-based hydrogels can be adjusted through crosslinking and by combining them with other materials. This review provides an overview of recent research on HAMA-based hydrogels for tissue engineering applications in orthopaedic diseases. First, we summarize the techniques for the preparation and characterization of HAMA hydrogels. Next, we offer a detailed review of the use of HAMA-based hydrogels in treating conditions such as cartilage injuries, bone defects, and meniscus injuries. Additionally, we discuss the applications of HAMA-based hydrogels in other diseases related to orthopaedics. Finally, we point out the challenges and propose future directions for the clinical translation of HAMA-based hydrogels.</div></div><div><h3>Translational potential statement</h3><div>HAMA-based hydrogels show strong translational potential in orthopaedics due to their biocompatibility, adjustable mechanical properties, and regenerative capabilities. With ongoing research, these hydrogels are well-positioned for clinical applications, particularly in cartilage repair, meniscus injuries, and osteoarthritis treatment.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"50 ","pages":"Pages 111-128"},"PeriodicalIF":5.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11779684/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143065586","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}

{"title":"Design of internal fixation implants for fracture: A review","authors":"Heng Zhang ,&nbsp;Shipeng Xu ,&nbsp;Xiaohong Ding ,&nbsp;Min Xiong ,&nbsp;Pengyun Duan","doi":"10.1016/j.jot.2024.09.012","DOIUrl":"10.1016/j.jot.2024.09.012","url":null,"abstract":"<div><div>Internal fixation is the most common and effective fracture treatment, and the design of Internal Fixation Implants (IFI) is important for fracture healing. In recent decades, IFI have been designed from the aspects of materials, geometry, fixation methods and functional characteristics. However, there has been no comprehensive summary on the evaluation method and design methods of IFI. This paper aims to review and analyze the key issues involved in the design of IFI, to provide references for IFI design. Firstly, the main factors affecting the healing effect are summarized and the design requirements of IFI are put forward through the analysis of fracture healing process. Secondly, the evaluation methods of IFI are compared and summarized, and the importance of evaluation methods based on fracture healing theory is emphasized. Subsequently, the properties and application scopes of common biomaterials for IFI are introduced. And the IFI, which is used widely, such as bone plate, intramedullary nail and embracing device, are summed up from the aspects of design factors and design methods. Highlight the distinctive contributions of additive manufacturing for the fabrication of implants and surface treatment for improving the multifunctionality of implants. Finally, the design concept of ideal IFI and the potential research content in the future are proposed based on the design requirements and the summary of the existing design studies.</div></div><div><h3>The translational potential of this article</h3><div>This study summarizes and analyzes the key issues involved in the design of IFI, which provide references for IFI design. A discussion on future research directions and suggestion were made, which is expected to advance the research in this field.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"50 ","pages":"Pages 306-332"},"PeriodicalIF":5.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143177845","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}

{"title":"Accelerated fracture healing accompanied with traumatic brain injury: A review of clinical studies, animal models and potential mechanisms","authors":"Zheyu Jin ,&nbsp;Ziyi Chen ,&nbsp;Tongzhou Liang ,&nbsp;Weiyang Liu ,&nbsp;Zhengming Shan ,&nbsp;Dianhui Tan ,&nbsp;Jiechen Chen ,&nbsp;Jun Hu ,&nbsp;Ling Qin ,&nbsp;Jiankun Xu","doi":"10.1016/j.jot.2024.10.008","DOIUrl":"10.1016/j.jot.2024.10.008","url":null,"abstract":"<div><div>The orthopaedic community frequently encounters polytrauma individuals with concomitant traumatic brain injury (TBI) and their fractures demonstrate accelerated fracture union, but the mechanisms remain far from clear. Animal and clinical studies demonstrate robust callus formation at the early healing process and expedited radiographical union. In humans, robust callus formation in TBI occurs independently of fracture fixation methods across multiple fracture sites. Animal studies of TBI replicate clinically relevant enlarged fracture callus as characterized by increased tissue volume and bone volume at the early stages. However, refinement and standardization of the TBI models requires further research. The quest for its underlying mechanisms began with the finding of increased osteogenesis <em>in vitro</em> using the serum and cerebral spinal fluid (CSF) from TBI individuals. This has led to the investigation of myriads of brain-derived factors including humoral factors, cytokines, exosomes, and mi-RNAs. Further, the emerging information of interplay between the skeletal system and central nervous system, the roles of peripheral nerves and their neuropeptides in regulating bone regeneration, offers valuable insights for future research. This review consolidates the findings from both experimental and clinical studies, elucidating the potential mechanisms underlying enhanced fracture healing in concurrent TBI scenarios that may lay down a foundation to develop innovative therapies for fracture healing enhancement and conquer fracture non-union.</div><div>The translational potential of this article.</div><div>This review comprehensively summarizes the observations of accelerated fracture healing in the presence of traumatic brain injury from both preclinical and clinical studies. In addition, it also delineates potential cellular and molecular mechanisms. Further detailed investigation into its underlying mechanisms may reveal innovative orthopaedic intervention strategies to improve fracture healing and thus offering promising avenues for future translational applications.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"50 ","pages":"Pages 71-84"},"PeriodicalIF":5.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11763218/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047030","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}

{"title":"Current advances in animal model of meniscal injury: From meniscal injury to osteoarthritis","authors":"Xiaoyao Peng,&nbsp;Fashuai Wu,&nbsp;Yuxiang Hu,&nbsp;Yangyang Chen,&nbsp;Yulong Wei,&nbsp;Weihua Xu","doi":"10.1016/j.jot.2024.11.005","DOIUrl":"10.1016/j.jot.2024.11.005","url":null,"abstract":"<div><div>Meniscal injury is a prevalent orthopedic practice that causes articular cartilage wear and degeneration due to tissue damage or loss, and may eventually result in the occurrence of knee osteoarthritis (KOA). Hence, investigating the structural regeneration and mechanical function restoration of the meniscus after injury is pivotal research topic for preventing KOA. Animal models are essential for investigating therapeutic strategies for meniscal injuries and their clinical translation, yet no current model can fully recapitulate the complexity of human meniscal injuries. This review aims to categorize the prevalent animal models of meniscal injury by their establishment methods, elucidate their principles and procedures, and discuss the suitability and limitations of each model. We delineate the pros and cons of different models in simulating the pathology and biomechanics of human meniscal injury. We also analyze different animal species regarding their meniscal structure, function, and repair potential, and their implications for model selection. We conclude that selecting an appropriate animal model requires a comprehensive consideration of various factors, such as research aims, anticipated outcomes, and feasibility. Furthermore, to translate novel therapeutic approaches to clinical applications more safely and effectively, future model development should emphasize aspects such as choosing animals of suitable age.</div><div>The Translational Potential of this Article: This review aims to categorize and discuss current animal models of meniscal injury by establishment methods and provides a comprehensive overview of the routinely employed experimental animals in each model to facilitate the clinical translation of OA-related research.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"50 ","pages":"Pages 388-402"},"PeriodicalIF":5.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143600497","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}

{"title":"Current status of nano-embedded growth factors and stem cells delivery to bone for targeted repair and regeneration","authors":"Wenqing Liang ,&nbsp;Chao Zhou ,&nbsp;Xiankun Liu ,&nbsp;Qiong Xie ,&nbsp;Linying Xia ,&nbsp;Lu Liu ,&nbsp;Wenwen Bao ,&nbsp;Hongming Lin ,&nbsp;Xiaochun Xiong ,&nbsp;Hao Zhang ,&nbsp;Zeping Zheng ,&nbsp;Jiayi Zhao","doi":"10.1016/j.jot.2024.12.006","DOIUrl":"10.1016/j.jot.2024.12.006","url":null,"abstract":"&lt;div&gt;&lt;div&gt;Bone-related diseases like osteoarthritis and osteoporosis impact millions globally, affecting quality of life. Osteoporosis considerably enhances the probability of bone fractures of the wrist, hip, and spine. Enhancement and acceleration of functional bone development can be achieved through the sustained delivery of growth factors (GFs) and cells in biomaterial carriers. The delivery of bioactive compounds in a targeted, spatiotemporal way that most closely resembles the natural defect repair process can be achieved by designing the carrier system with established release kinetics. Furthermore, the carrier can serve as a substrate that mimics the extracellular matrix, facilitating osteoprogenitor cell infiltration and growth for integrative tissue healing. In this report, we explore the significance of GFs within the realm of bone and cartilage tissue engineering, encompassing their encapsulation and delivery methodologies, the kinetics of release, and their amalgamation with biomaterials and stem cells (SCs) to facilitate the mending of bone fractures. Moreover, the significance of GFs in evaluating the microenvironment of bone tissue through reciprocal signaling with cells and biomaterial scaffolds is emphasized which will serve as the foundation for prospective advances in bone and cartilage tissue engineering as well as therapeutic equipment. Nanoparticles are being used in regenerative medicine to promote bone regeneration and repair by delivering osteoinductive growth factors like BMP-2, VEGF, TGF-β. These nanocarriers allow controlled release, minimizing adverse effects and ensuring growth factors are concentrated at the injury site. They are also mixed with mesenchymal stem cells (MSCs) to improve their engraftment, differentiation, and survival. This approach is a key step in developing multi-model systems that more efficiently facilitate bone regeneration. Researchers are exploring smart nanoparticles with immunomodulatory qualities to improve bonre regeneration and reduce inflammation in injury site. Despite promising preclinical results, challenges include cost management, regulatory approval, and long term safety. However, incorporating stem cell transport and growth factors in nanoparticles could revolutionize bone regeneration and offer more personalized therapies for complex bone disorders and accidents.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;The translational potential of this article&lt;/h3&gt;&lt;div&gt;Stem cell transport and growth factors encapsulated in nanoparticles are becoming revolutionary methods for bone regeneration and repair. By encouraging stem cells to develop into osteoblasts, osteoinductive GFs like BMP-2, VEGF, and TGF-β can be delivered under control due to nanomaterials like nanoparticles, nanofibers, and nanotubes. By ensuring sustained release, these nanocarriers lessen adverse effects and enhance therapeutic results. In order to prove their survival and development, MCSs, which are essential for bone regeneration, are mixe","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"50 ","pages":"Pages 257-273"},"PeriodicalIF":5.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11788687/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122818","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}

{"title":"LRP1 mitigates intervertebral disc degeneration by inhibiting endoplasmic reticulum stress through stabilizing the PPARγ","authors":"Dengbo Yao ,&nbsp;Ming Li ,&nbsp;Weike Zeng ,&nbsp;Kun Wang ,&nbsp;Zhuangyao Liao ,&nbsp;Enming Chen ,&nbsp;Tong Xing ,&nbsp;Yuwei Liang ,&nbsp;Jun Tang ,&nbsp;Guoming Wen ,&nbsp;Qing Ning ,&nbsp;Yuxi Li ,&nbsp;Lin Huang","doi":"10.1016/j.jot.2024.12.009","DOIUrl":"10.1016/j.jot.2024.12.009","url":null,"abstract":"<div><h3>Background</h3><div>Intervertebral disc degeneration (IDD) is a significant cause of lower back pain, characterized by inflammation-mediated extracellular matrix (ECM) degradation, apoptosis, and aging of nucleus pulposus (NP) cells. Identifying key regulatory targets for these processes is crucial for IDD treatment. Previous research has highlighted the role of low-density lipoprotein receptor-related protein 1 (LRP1) in regulating ECM levels and cell fate, but its role in IDD remains under-explored. This study aims to elucidate the function and mechanism of LRP1 in the progression of IDD.</div></div><div><h3>Methods</h3><div>LRP1 expression was assessed in clinical tissue samples from patients diagnosed with IDD and in a rat IDD model established using needle puncture injuries. The effects of LRP1 knockdown and treatment with the LRP1 activator SP16 on apoptosis and ECM metabolism in NP cells were analyzed, with a focus on their relationship with endoplasmic reticulum (ER) stress. The interaction and regulatory mechanism between LRP1 and peroxisome proliferator-activated receptor gamma (PPARγ) were further explored to clarify how LRP1 regulates ER stress. Finally, the in vivo therapeutic effect of SP16 was investigated using a rat tail IDD model.</div></div><div><h3>Results</h3><div>We found that LRP1 expression was significantly downregulated in IDD. In NP cells with LRP1 knockdown, there was a marked increase in apoptosis and detrimental ECM remodeling, which were associated with the activation of ER stress. Our research further revealed that LRP1 interacts with PPARγ, stabilizing the PPARγ protein and preventing its lysosomal degradation, thereby mitigating ER stress. Activation of LRP1 in our models significantly reduced ER stress, matrix degradation, and apoptosis, thereby attenuating IDD both in vitro and in vivo.</div></div><div><h3>Conclusion</h3><div>This study systematically investigated the role and mechanisms of the LRP1/PPARγ/ER stress signaling axis in IDD. Our findings suggest that targeting LRP1 to modulate this signaling pathway could provide a promising therapeutic approach for the treatment of IDD.</div></div><div><h3>The Translational potential of this Article</h3><div>Our study demonstrated that LRP1 can reduce apoptosis and ECM degradation by inhibiting ER stress through stabilizing PPARγ, indicating that targeting LRP1 may be a novel therapeutic strategy for IDD.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"50 ","pages":"Pages 196-210"},"PeriodicalIF":5.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11786795/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080350","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}

{"title":"Moderate static magnetic field regulates iron metabolism and salvage bone loss caused by iron accumulation","authors":"Chenxiao Zhen ,&nbsp;Shenghang Wang ,&nbsp;Jiancheng Yang ,&nbsp;Gejing Zhang ,&nbsp;Chao Cai ,&nbsp;Jianping Wang ,&nbsp;Aifei Wang ,&nbsp;Youjia Xu ,&nbsp;Yanwen Fang ,&nbsp;Min Wei ,&nbsp;Dachuan Yin ,&nbsp;Xinle Luo ,&nbsp;Ming Gong ,&nbsp;Hao Zhang ,&nbsp;Peng Shang","doi":"10.1016/j.jot.2024.10.012","DOIUrl":"10.1016/j.jot.2024.10.012","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Objective&lt;/h3&gt;&lt;div&gt;Clinical studies, epidemiological investigations and animal experiments have demonstrated that iron overload lead to bone loss, especially postmenopausal osteoporosis. As a physiotherapy tool, electromagnetic fields already used in clinical treatment of osteoporosis and participates in bone remodeling by affecting the iron metabolism of organisms. As an electromagnetic field with constant magnetic flux density and direction, the mechanism of static magnetic field (SMF) regulating iron metabolism remains unclear. Therefore, the aim of this study was to investigate the effects of moderate static magnetic field (MMF) on iron metabolism and bone metabolism in postmenopausal osteoporosis and &lt;em&gt;HAMP&lt;/em&gt;-deficient mouse models, and to elucidate the underlying mechanisms.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Firstly, the effects of MMF on bone metabolism and iron metabolism in 22 postmenopausal osteoporosis participants were evaluated by comparing the changes of bone mineral density (BMD) and serum ferritin before and after treatment. Secondly, 10-week-old male C57BL/6 &lt;em&gt;HAMP&lt;/em&gt;&lt;sup&gt;+/+&lt;/sup&gt; and &lt;em&gt;HAMP&lt;/em&gt;&lt;sup&gt;−/−&lt;/sup&gt; mice were randomly divided into four groups, namely GMF-&lt;em&gt;HAMP&lt;/em&gt;&lt;sup&gt;+/+&lt;/sup&gt; group and MMF-&lt;em&gt;HAMP&lt;/em&gt;&lt;sup&gt;+/+&lt;/sup&gt; group, GMF-&lt;em&gt;HAMP&lt;/em&gt;&lt;sup&gt;−/−&lt;/sup&gt; group and MMF-&lt;em&gt;HAMP&lt;/em&gt;&lt;sup&gt;−/−&lt;/sup&gt; group (n = 8/group). The MMF-treated mice were exposed daily to MMF, while the remaining group was exposed to geomagnetic field (GMF) for 8 weeks. BMD was scanned and bone tissues were collected for mechanical, structural and histological analysis. In addition, analysis of serum and tissue iron content evaluated the regulation of systemic iron metabolism by MMF. Finally, the effects of MMF on the differentiation of primary macrophages and primary osteoblasts were evaluated &lt;em&gt;in vitro&lt;/em&gt;.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;In clinical trial, MMF decreased serum ferritin levels in postmenopausal osteoporosis patients, which was negatively correlated with changes in lumbar BMD. &lt;em&gt;In vivo&lt;/em&gt;, the results showed that &lt;em&gt;HAMP&lt;/em&gt;-deficient mice were accompanied by iron overload, along with reduced lumbar vertebra bone mass and bone quality. MMF improved the bone mass, microstructure and biomechanical properties of lumbar vertebrae in &lt;em&gt;HAMP&lt;/em&gt;&lt;sup&gt;−/−&lt;/sup&gt; mice. &lt;em&gt;In vitro&lt;/em&gt;, MMF reduced the number and differentiation of osteoclasts in &lt;em&gt;HAMP&lt;/em&gt;&lt;sup&gt;−/−&lt;/sup&gt; mice, and promoted primary osteoblast differentiation by activating Wnt/β-catenin signaling pathway. Further, MMF also reduced the iron ion conversion and enhanced the antioxidant system of &lt;em&gt;HAMP&lt;/em&gt;&lt;sup&gt;−/−&lt;/sup&gt; mice. These data suggested that MMF could regulate iron metabolism and salvage bone loss caused by iron accumulation.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;The clinical trial and laboratory results suggested that MMF intervention has a protective effect on bone loss caused by iron metabolism disorders.&lt;/di","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"50 ","pages":"Pages 144-157"},"PeriodicalIF":5.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143179168","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}