Journal of Orthopaedic Translation最新文献

{"title":"Gradient scaffolds in bone-soft tissue interface engineering: Structural characteristics, fabrication techniques, and emerging trends","authors":"Ying Liu ,&nbsp;Yue Wan ,&nbsp;Chaojing Li ,&nbsp;Guoping Guan ,&nbsp;Fujun Wang ,&nbsp;Jing Gao ,&nbsp;Lu Wang","doi":"10.1016/j.jot.2024.10.015","DOIUrl":"10.1016/j.jot.2024.10.015","url":null,"abstract":"<div><div>Bone and soft tissues are connected by a complex interface that is crucial for the smooth transfer of mechanical stress. Effective repair of this interface requires bio-scaffolds specifically designed to support the regeneration of diverse cell types and signalling molecules. With advances in micro- and nanotechnologies, gradient biomaterial scaffolds have demonstrated significant potential in interface tissue regeneration. This paper reviews the structure of the bone-soft tissue interface, the various gradient scaffold types, and construction methods. It also discusses the recent developments and future directions in interface tissue engineering, emphasizing the potential of gradient scaffolds to restore the natural structure and function of bone-soft tissue interfaces. Overall, this paper provides valuable insights into the application of gradient scaffolds for bone-soft tissue interface engineering, offering inspiration for biomimetic approaches to soft-hard interface repair in future medical engineering.</div></div><div><h3>The Translational Potential of this Article</h3><div>First, the emphasis on gradient scaffolds could significantly impact clinical practices related to bone-soft tissue integration, ultimately improving patient outcomes and quality of life. Second, it also aligns with the growing trend of biomimetic approaches in medical engineering, potentially inspiring new innovations in bone-soft tissue repair strategies.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"50 ","pages":"Pages 333-353"},"PeriodicalIF":5.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143177846","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":"Single-cell transcriptomics identifies the common perturbations of monocyte/macrophage lineage cells in inflammaging of bone marrow","authors":"Peng Liao ,&nbsp;Sihan Tong ,&nbsp;Lin Du ,&nbsp;Jiong Mei ,&nbsp;Bingqi Wang ,&nbsp;Yafei Lu ,&nbsp;Meng Yao ,&nbsp;Changqing Zhang ,&nbsp;Delin Liu ,&nbsp;Zhigang Zhong ,&nbsp;Fang Ye ,&nbsp;Junjie Gao","doi":"10.1016/j.jot.2024.09.013","DOIUrl":"10.1016/j.jot.2024.09.013","url":null,"abstract":"<div><h3>Background</h3><div>Bone marrow inflammaging is a low-grade chronic inflammation that induces bone marrow aging. Multiple age-related and inflammatory diseases involve bone marrow inflammaging. Whether common pathological pathways exist in bone marrow inflammaging remains unclear.</div></div><div><h3>Methods</h3><div>We collected bone marrow from telomerase-deficient mice (telomerase RNA component, TERC^ko/ko), 5 × FAD mice and <em>Dmp1</em>^<em>Cre</em><em>-DTA</em>^{<em>ki/wt</em>} mice and High-fat diet-fed mice (HFD), and lumbar 5 nerve compression mice. We performed scRNA-Seq analysis on bone marrow obtained from these mouse models to investigate the potential shared pathway of bone marrow inflammation.</div></div><div><h3>Results</h3><div>We identified the monocyte/macrophage lineage was activated via the App-Cd74 axis in multiple aging and inflammatory mouse models. Increased expression of CD38 and Ly6a, and decreased expression of Col1a and Lif in macrophages serve as shared changes in different mouse models. The activated macrophages, interacting with other cells, control the expansion of B cells via the CD52-Siglec-G axis. The Ccl6-Ccr2 and Ccl9-Ccr1 ligand-receptor pairs, along with Fn1 and C3-related pathways in macrophages, were associated with immune cell activation and the recruitment of lymphocytes. Interactions with mesenchymal cells were enriched for integrins (Itga4), Fn1, and adhesion molecules (Vcam1).</div></div><div><h3>Conclusion</h3><div>Our study demonstrates that monocyte/macrophage lineage stimulation is a key event in bone marrow inflammaging. We identified common differentially expressed genes and activated pathways in this lineage, suggesting potential targets for future interventions.</div></div><div><h3>The translational potential of this article</h3><div>Our study revealed shared genes and ligand-receptor pairs in the activated monocyte/macrophage lineage within inflammaging bone marrow. These findings offer potential therapeutic targets for cell-specific anti-inflammatory treatments.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"50 ","pages":"Pages 85-96"},"PeriodicalIF":5.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762928/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047035","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":"Clinical and omics biomarkers in osteoarthritis diagnosis and treatment","authors":"Muhai Deng ,&nbsp;Cong Tang ,&nbsp;Li Yin ,&nbsp;Yunsheng Jiang ,&nbsp;Yang Huang ,&nbsp;Yong Feng ,&nbsp;Cheng Chen","doi":"10.1016/j.jot.2024.12.007","DOIUrl":"10.1016/j.jot.2024.12.007","url":null,"abstract":"<div><div>Osteoarthritis (OA) is a prevalent degenerative joint disease that significantly impacts the quality of life for hundreds of millions, and is a major cause of disability. Despite this, diagnostic and therapeutic options for OA are still limited. With advances in molecular biology, an increasing number of OA biomarkers have been identified, which not only enhances our understanding of OA pathogenesis, but also offers new approaches for OA diagnosis and treatment. This review discussed the research progress on traditional OA biomarkers, and analyzed the application of various omics, including genomics, transcriptomics, proteomics, and metabolomics, in the diagnosis and treatment of OA. Furthermore, we explored how integrating multi-omics methods can reveal interactions among different biomolecules and their roles in the development of OA. This emerging interdisciplinary approach not only provides a more comprehensive understanding of the fundamental biological characteristics of OA, but also aids in identifying new integrated biomarkers, thereby allowing for more accurate predictions of disease progression and treatment responses. The identification and development of biomarkers offer new perspectives in understanding OA, enhancing the specificity and sensitivity of biological diagnostic markers, providing a basis for the design of targeted drugs, and ultimately advancing the development of precision diagnosis and treatment strategies in clinical OA.</div><div>This study provides an overview of both commonly used and emerging biomarkers of OA which is beneficial for a more accurate, timely, effective clinical diagnosis and treatment for OA.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"50 ","pages":"Pages 295-305"},"PeriodicalIF":5.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143177862","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":"Sirt1 blocks nucleus pulposus and macrophages crosstalk by inhibiting RelA/Lipocalin 2 axis","authors":"Yi-Fan Wei ,&nbsp;He-Long Zhang ,&nbsp;Ling-Zhi Li ,&nbsp;You Lv ,&nbsp;He Li ,&nbsp;Zhi Li ,&nbsp;Feng-Lei Yu ,&nbsp;Tao Jiang ,&nbsp;Tian-You Zhang ,&nbsp;Feng Xin ,&nbsp;Cheng Ma ,&nbsp;Yong-Xin Ren","doi":"10.1016/j.jot.2024.11.008","DOIUrl":"10.1016/j.jot.2024.11.008","url":null,"abstract":"<div><h3>Background</h3><div>Intervertebral disc degeneration (IVDD) stands as a primary pathophysiological driver of low back pain, yet no therapeutic intervention effectively arrests its progression. Evidence shows that certain Sirt1 agonists may confer protective effects on intervertebral discs, but the underlying mechanisms remain unclear. This study aims to delineate the interaction between Sirt1 and the inflammatory microenvironment, offering potential novel avenues for IVDD prevention and treatment.</div></div><div><h3>Methods</h3><div><em>In vitro</em> IL-1β-induced nucleus pulposus cells (NPCs) degenerative model and <em>in vivo</em> a mouse annulus fibrosus needle puncture model in Sirt1 transgenic (Sirt1^TG) and the same litter WT mice were used to investigate the role of Sirt1 in homeostasis and inflammation. Mechanistic insights were obtained through RNA sequencing, co-immunoprecipitation (Co-IP), luciferase assays, and chromatin immunoprecipitation-(ChIP)-PCR. A co-culture system of Raw264.7 and NPCs was employed to assess the involvement of Lipocalin 2.</div></div><div><h3>Results</h3><div>Our study demonstrated reduced Sirt1 expression in degenerating human nucleus pulposus (NP) tissue. Both <em>in vitro</em> and <em>in vivo</em> data revealed that NP-specific overexpression of Sirt1 inhibited extracellular matrix degradation and inflammation. Mechanistically, Sirt1 suppressed the acetylation of RelA/p65 at lysine 310 and phosphorylation at serine 536, with the C-terminus of Sirt1 and the RHD-NLS domain of RelA mediating to their interaction. Furthermore, NPCs-derived Lipocalin 2 was identified as a cytokine involved in macrophage chemotaxis and M1 polarization to exacerbate inflammation.</div></div><div><h3>Conclusion</h3><div>Our work revealed that Sirt1 negatively regulates Lipocalin 2, thereby ameliorating the inflammatory milieu and blocking NPCs and macrophages crosstalk.</div></div><div><h3>The Translational Potential of this Article</h3><div>This study illuminates the crucial role and molecular mechanisms of Sirt1 in regulating the NP microenvironment. These insights shed light on strategies for the prevention and treatment of IVDD-related herniation and low back pain. By pinpointing specific biological targets, the screening of smallmolecule compounds with significant clinical implications can be facilitated. This translational innovation promises to optimize cells communication within intervertebral disc microenvironment via localized drug delivery, potentially improving patient outcomes and satisfaction following spinal fusion or discectomy surgeries.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"50 ","pages":"Pages 30-43"},"PeriodicalIF":5.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11699611/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142931269","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":"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":"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":"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}