Journal of Orthopaedic Translation最新文献

{"title":"Global, regional, national trends of femur fracture and machine learning prediction: Comprehensive findings and questions from global burden of disease 1990–2019","authors":"Jinyi Wu ,&nbsp;Yanjun Che ,&nbsp;Yue Zhang ,&nbsp;Junwen Wang ,&nbsp;Ming Chen ,&nbsp;Jun Jiang ,&nbsp;Qingwu Jiang ,&nbsp;Yibiao Zhou","doi":"10.1016/j.jot.2024.03.002","DOIUrl":"https://doi.org/10.1016/j.jot.2024.03.002","url":null,"abstract":"<div><h3>Background</h3><p>Femur fracture is a type of fracture with high disability and mortality. There is no comprehensive analysis and prediction of the global distribution of femur fractures, so we conducted this study.</p></div><div><h3>Methods</h3><p>Age-standardized incidence rate (ASIR), age-standardized prevalence rate (ASPR), and years living with disability (YLDs) of femur fractures (excluding femoral neck) were downloaded from the Global burden of disease database. Trend analysis was performed, and 6 time-series machine learning algorithms were applied to predict the global ASIR, ASPR, and YLDs.</p></div><div><h3>Results</h3><p>ASPR for femur fracture had been increasing in most countries worldwide from 1990 to 2019, with the highest in East Asia (AAPC = 1.25 95%Confidence Interval (1.2, 1.3)) and lowest in Central Latin America (AAPC = −0.74 95%CI (−0.81, −0.67)). However, ASIR showed a significant downward trend worldwide, with East Saharan Africa decreasing the most (AAPC = −4.04 95%CI (−5.56, −2.47)), and East Asia elevating the most (AAPC = 1.11 95%CI (0.87, 1.42)). YLDs were increasing over the world, with East Asia still elevating the most AAPC= (3.9 95%CI (3.85, 3.95)), with the only region of decrease being Eastern Europe (AAPC = −0.28 95%CI (−0.3, −0.26)). Both ASPR and ASIR were higher in women than in men in the &gt;75 year group, whereas YLDs was lower in women than in men in the &gt;60 year group. Globally, the ARIMA model was optimal in the prediction of ASPR, the PROPHET model effected in the prediction of ASIR, and the PROPHET WITH XGBOOST model was the best in the prediction of YLDs. The projections showed increase in both ASPR and YLDs, except for ASIR decreasing by 2030.</p></div><div><h3>Conclusions</h3><p>Our study found a rise in femur fracture ASPR and ASIR from 1990 to 2019 in war conflict areas and East Asia, meanwhile, the YLDs of femur fracture increased in populous countries. In both 1990 and 2019, both ASPR and ASIR were higher in women over 75 years than that in men, but YLDs was higher in men over 60 years than that in women. In 2020–2030, while global femur fracture ASIR might decline, both ASPR and YLDs might rise.</p></div><div><h3>The Translational Potential of this article</h3><p>Femur fracture is a high-energy injury due to direct violence, and in war, conflicting and underdeveloped regions such as East Asia. Accidental injuries may occur due to the rapid development of industry and the frequent traffic accidents. This study suggests that we should focus on elderly women (≥75 years) in the above regions in the future. For older men (&gt;60 years old), more attention should be paid to post-fracture functional rehabilitation and early reintegration into society to reduce the disability rate and lower the socio-economic burden.</p></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"46 ","pages":"Pages 46-52"},"PeriodicalIF":6.6,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214031X24000263/pdfft?md5=b9814b591ace9bd721022d2348397b9a&pid=1-s2.0-S2214031X24000263-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140950917","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":"YAP maintains cartilage stem/progenitor cell homeostasis in osteoarthritis","authors":"Lina Zhang ,&nbsp;Xinxing Wang ,&nbsp;Guang Xia ,&nbsp;Junjie Huang ,&nbsp;Zi Wen ,&nbsp;Chi Liang ,&nbsp;Xu Cao ,&nbsp;Yong Zhou ,&nbsp;Song Wu","doi":"10.1016/j.jot.2024.03.004","DOIUrl":"https://doi.org/10.1016/j.jot.2024.03.004","url":null,"abstract":"<div><h3>Background</h3><p>The cartilage stem/progenitor cells (CSPC) play a critical role in maintaining cartilage homeostasis. However, the effects of phenotypic fluctuations of CSPC on cartilage degeneration and the role of CSPC in the pathogenesis of OA is largely unknown.</p></div><div><h3>Methods</h3><p>The cartilage samples of 3 non-OA and 10 OA patients were collected. Human CSPC (hCSPC) derived from these patients were isolated, identified, and evaluated for cellular functions. Additionally, chondrocytes derived from OA patients were isolated. The effect of Yes-associated protein (YAP) expression on hCSPC was investigated <em>in vitro</em>. The OA rat model was established by Hulth's method. Lentivirus-mediated YAP (Lv-YAP) or lentivirus-mediated YAP RNAi (Lv-YAP-RNAi) was injected intra-articularly to modulate YAP expression in rat joints. In addition, allogeneic rat CSPC (rCSPC) overexpressing or silencing YAP were transplanted by intra-articularly injection. We also evaluated the functions of rCSPC and the OA-related cartilage phenotype in the rat model. Finally, the transcriptome of OA rCSPC overexpressing YAP was examined to explore the potential downstream targets of YAP in rCSPC.</p></div><div><h3>Results</h3><p>hCSPC derived from OA patients exhibited differential chondrogenesis capacity. Among them, a subset of hCSPC showed pronounced dysfunction, including impaired chondrogenic differentiation, inhibition of proliferation and migration, and downregulation of lubricin. Additionally, YAP was lowly expressed in quiescent non-OA hCSPC, upregulated in activated OA hCSPC, but significantly downregulated in dysfunctional OA hCSPC. Notably, the overexpression of YAP in OA hCSPC improved the proliferation, lubricin production, cell migration, and senescence, while silencing YAP had the opposite effect. In vivo, upregulation of YAP in the joint delayed OA progression and improved the cartilage regeneration capacity of rCSPC. Using transcriptomic analysis, we found that YAP may regulate rCSPC function by upregulating Baculoviral IAP repeat-containing 2 (BIRC2). Importantly, the knockdown of BIRC2 partly blocked the regulation of YAP on the CSPC function.</p></div><div><h3>Conclusion</h3><p>Dysfunction of CSPC compromises the intrinsic repair capacity of cartilage and impairs cartilage homeostasis in OA. Notably, the transcriptional co-activator YAP plays a critical role in maintaining CSPC function through potential target gene BIRC2.</p></div><div><h3>The Translational Potential of this Article</h3><p>In this study, we observed targeting the YAP-BIRC2 axis improved the CSPC function and restored the cartilage homeostasis in OA. This study provides a potential stem cell-modifying OA therapy.</p></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"46 ","pages":"Pages 79-90"},"PeriodicalIF":6.6,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214031X24000299/pdfft?md5=0b62e06315d07b53f23f0b498aa8c1ac&pid=1-s2.0-S2214031X24000299-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141083808","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":"Aging and musculoskeletal health","authors":"Tingting Tang","doi":"10.1016/j.jot.2024.05.006","DOIUrl":"https://doi.org/10.1016/j.jot.2024.05.006","url":null,"abstract":"","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"46 ","pages":"Pages A1-A2"},"PeriodicalIF":6.6,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214031X24000482/pdfft?md5=0af013808d5dd681af67e7eceb9658e2&pid=1-s2.0-S2214031X24000482-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141314163","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":"Decellularized laser micro-patterned osteochondral implants exhibit zonal recellularization and self-fixing for osteochondral regeneration in a goat model","authors":"Haoye Meng ,&nbsp;Xuejian Liu ,&nbsp;Ronghui Liu ,&nbsp;Yudong Zheng ,&nbsp;Angyang Hou ,&nbsp;Shuyun Liu ,&nbsp;Wei He ,&nbsp;Yu Wang ,&nbsp;Aiyuan Wang ,&nbsp;Quanyi Guo ,&nbsp;Jiang Peng","doi":"10.1016/j.jot.2024.04.005","DOIUrl":"https://doi.org/10.1016/j.jot.2024.04.005","url":null,"abstract":"<div><h3>Background</h3><p>Osteochondral regeneration has long been recognized as a complex and challenging project in the field of tissue engineering. In particular, reconstructing the osteochondral interface is crucial for determining the effectiveness of the repair. Although several artificial layered or gradient scaffolds have been developed recently to simulate the natural interface, the functions of this unique structure have still not been fully replicated. In this paper, we utilized laser micro-patterning technology (LMPT) to modify the natural osteochondral “plugs” for use as grafts and aimed to directly apply the functional interface unit to repair osteochondral defects in a goat model.</p></div><div><h3>Methods</h3><p>For in vitro evaluations, the optimal combination of LMPT parameters was confirmed through mechanical testing, finite element analysis, and comparing decellularization efficiency. The structural and biological properties of the laser micro-patterned osteochondral implants (LMP-OI) were verified by measuring the permeability of the interface and assessing the recellularization processes. In the goat model for osteochondral regeneration, a conical frustum-shaped defect was specifically created in the weight-bearing area of femoral condyles using a customized trephine with a variable diameter. This unreported defect shape enabled the implant to properly self-fix as expected.</p></div><div><h3>Results</h3><p>The micro-patterning with the suitable pore density and morphology increased the permeability of the LMP-OIs, accelerated decellularization, maintained mechanical stability, and provided two relative independent microenvironments for subsequent recellularization. The LMP-OIs with goat's autologous bone marrow stromal cells in the cartilage layer have securely integrated into the osteochondral defects. At 6 and 12 months after implantation, both imaging and histological assessments showed a significant improvement in the healing of the cartilage and subchondral bone.</p></div><div><h3>Conclusion</h3><p>With the natural interface unit and zonal recellularization, the LMP-OI is an ideal scaffold to repair osteochondral defects especially in large animals.</p></div><div><h3>The translational potential of this article</h3><p>These findings suggest that such a modified xenogeneic osteochondral implant could potentially be explored in clinical translation for treatment of osteochondral injuries. Furthermore, trimming a conical frustum shape to the defect region, especially for large-sized defects, may be an effective way to achieve self-fixing for the implant.</p></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"46 ","pages":"Pages 18-32"},"PeriodicalIF":6.6,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214031X24000421/pdfft?md5=accc0f1e9f084a3ffec7c5b50e01064e&pid=1-s2.0-S2214031X24000421-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140900921","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":"SPARCL1 promotes chondrocytes extracellular matrix degradation and inflammation in osteoarthritis via TNF/NF-κB pathway","authors":"Yu Miao ,&nbsp;Shenghui Wu ,&nbsp;Ziling Gong ,&nbsp;Yiwei Chen ,&nbsp;Feng Xue ,&nbsp;Kexin Liu ,&nbsp;Jian Zou ,&nbsp;Yong Feng ,&nbsp;Guangyi Li","doi":"10.1016/j.jot.2024.02.009","DOIUrl":"https://doi.org/10.1016/j.jot.2024.02.009","url":null,"abstract":"<div><h3>Objectives</h3><p>SPARCL1 is a matricellular protein that mediates the cell–matrix interactions and participates in physiological processes such as cell adhesion, differentiation and proliferation. However, its role in chondrocyte and osteoarthritis (OA) progression has not been fully characterized. We aimed to evaluate the effects of SPARCL1 on OA through in vitro and <em>in vivo</em> experiments.</p></div><div><h3>Methods</h3><p>Expression of SPARCL1 was examined in 55 paired human OA samples. Effects of Sparcl1 on chondrocytes were identified in vitro. Intra-articular injection was performed in an anterior cruciate ligament transection (ACLT) mouse model. Alterations of SPARCL1-mediated signaling pathway were identified by RNA-seq analysis. qPCR and western-blot were used to demonstrate the potential signaling pathway.</p></div><div><h3>Results</h3><p>SPARCL1 expression in the OA cartilage was increased compared with undamaged cartilage. Recombinant Sparcl1 protein induced extracellular matrix degradation in chondrocytes. Furthermore, intra-articular injection of recombinant Sparcl1 protein in ACLT mice could promote OA pathogenesis. Mechanistically, Sparcl1 activated TNF/NF-κB pathway and consequently led to increased transcription of inflammatory factors and catabolism genes of cartilage, which could be reversed by NF-κB inhibitor BAY 11–7082.</p></div><div><h3>Conclusion</h3><p>SPARCL1 could promote extracellular matrix degradation and inflammatory response to accelerate OA progression via TNF/NF-κB pathway.</p></div><div><h3>The translational potential of this article</h3><p>The current research could help to gain further insights into the underlying molecular mechanism in OA development, and provides a biological rationale for the use of SPARCL1 as a potential therapeutic target of OA.</p></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"46 ","pages":"Pages 116-128"},"PeriodicalIF":6.6,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214031X24000287/pdfft?md5=effeaf6d49eea846f1d729be0ef9b128&pid=1-s2.0-S2214031X24000287-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141164440","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":"Metformin prevents mandibular bone loss in a mouse model of accelerated aging by correcting dysregulated AMPK-mTOR signaling and osteoclast differentiation","authors":"Boyang Liu ,&nbsp;Jiao Zhang ,&nbsp;Jinge Zhang ,&nbsp;Xiaolei Ji ,&nbsp;Rong Wang ,&nbsp;Aixiu Gong ,&nbsp;Dengshun Miao","doi":"10.1016/j.jot.2024.03.001","DOIUrl":"https://doi.org/10.1016/j.jot.2024.03.001","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;p&gt;Age-related mandibular osteoporosis frequently causes loose teeth, difficulty eating, and disfiguration in elders. Bmi1&lt;sup&gt;−/−&lt;/sup&gt; mice displaying accelerated skeletal aging represent a useful model for testing interventions against premature jaw bone loss. As an anti-aging agent, metformin may ameliorate molecular dysfunction driving osteoporosis pathogenesis. We explored the mechanisms of mandibular osteopenia in Bmi1&lt;sup&gt;−/−&lt;/sup&gt; mice and prevention by metformin treatment.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;p&gt;Three mouse groups were utilized: wild-type controls, untreated Bmi1&lt;sup&gt;−/−&lt;/sup&gt;, and Bmi1&lt;sup&gt;−/−&lt;/sup&gt; receiving 1 g/kg metformin diet. Mandibular bone phenotype was assessed by X-ray, micro-CT, histology, and immunohistochemistry. AMPK-mTOR pathway analysis, senescence markers, osteoblast and osteoclast gene expression were evaluated in jaw tissue. Osteoclast differentiation capacity and associated signaling molecules were examined in cultured Bmi1&lt;sup&gt;−/−&lt;/sup&gt; bone marrow mononuclear cells ± metformin.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;p&gt;Bmi1 loss reduced mandible bone density concomitant with decreased AMPK activity, increased mTOR signaling and cellular senescence in jaw tissue versus wild-type controls. This was accompanied by impaired osteoblast function and upregulated osteoclastogenesis markers. Metformin administration normalized AMPK-mTOR balance, oxidative stress and senescence signaling to significantly improve mandibular bone architecture in Bmi1&lt;sup&gt;−/−&lt;/sup&gt; mice. In culture, metformin attenuated excessive osteoclast differentiation from Bmi1&lt;sup&gt;−/−&lt;/sup&gt; marrow precursors by correcting dysregulated AMPK-mTOR-p53 pathway activity and suppressing novel pro-osteoclastogenic factor Stfa1.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;p&gt;Our study newly demonstrates metformin prevents accelerated jaw bone loss in a premature aging murine model by rectifying molecular dysfunction in cellular energy sensors, redox state, senescence and osteoclastogenesis pathways. Targeting such age-associated mechanisms contributing to osteoporosis pathogenesis may help maintain oral health and aesthetics in the growing elderly population.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Translational potential&lt;/h3&gt;&lt;p&gt;The pronounced mandibular osteopenia exhibited in Bmi1&lt;sup&gt;−/−&lt;/sup&gt; mice represents an accelerated model of jaw bone deterioration observed during human aging. Our finding that metformin preserves mandibular bone integrity in this progeroid model has important clinical implications. As an inexpensive oral medication already widely used to manage diabetes, metformin holds translational promise for mitigating age-related osteoporosis. The mandible is essential for chewing, swallowing, speech and facial structure, but progressively loses bone mass and strength with advancing age, significantly impacting seniors' nutrition, physical function and self-image. Our results suggest metformin's ability to rectify cellular energy imbalance, oxidative str","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"46 ","pages":"Pages 129-142"},"PeriodicalIF":6.6,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214031X24000251/pdfft?md5=79d26fac88a2c5498e49b75231a25415&pid=1-s2.0-S2214031X24000251-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141164441","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":"l-arginine promotes angio-osteogenesis to enhance oxidative stress-inhibited bone formation by ameliorating mitophagy","authors":"Yang Shen ,&nbsp;Haoming Wang ,&nbsp;Hongwei Xie ,&nbsp;Jiateng Zhang ,&nbsp;Qingliang Ma ,&nbsp;Shiyu Wang ,&nbsp;Putao Yuan ,&nbsp;Hong Xue ,&nbsp;Huaxing Hong ,&nbsp;Shunwu Fan ,&nbsp;Wenbin Xu ,&nbsp;Ziang Xie","doi":"10.1016/j.jot.2024.03.003","DOIUrl":"https://doi.org/10.1016/j.jot.2024.03.003","url":null,"abstract":"<div><h3>Background</h3><p>Osteoporosis is one of the most common bone diseases in middle-aged and elderly populations worldwide. The development of new drugs to treat the disease is a key focus of research. Current treatments for osteoporosis are mainly directed at promoting osteoblasts and inhibiting osteoclasts. However, there is currently no ideal approach for osteoporosis treatment. <span>l</span>-arginine is a semi-essential amino acid involved in a number of cellular processes, including nitric production, protein biosynthesis, and immune responses. We previously reported that <span>l</span>-arginine-derived compounds can play a regulatory role in bone homeostasis.</p></div><div><h3>Purpose</h3><p>To investigate the specific effect of <span>l</span>-arginine on bone homeostasis.</p></div><div><h3>Methods</h3><p>Mildly aged and ovariectomized mouse models were used to study the effects of <span>l</span>-arginine on osteogenesis and angiogenesis, assessed by micro-computed tomography and immunostaining of bone tissue. The effect of <span>l</span>-arginine on osteogenesis, angiogenesis, and adipogenesis was further studied in vitro using osteoblasts obtained from cranial cap bone, endothelial cells, and an adipogenic cell line. Specific methods to assess these processes included lipid staining, cell migration, tube-forming, and wound-healing assays. Protein and mRNA expression was determined for select biomarkers.</p></div><div><h3>Results</h3><p>We found that <span>l</span>-arginine attenuated bone loss and promoted osteogenesis and angiogenesis. <span>l</span>-arginine increased the activity of vascular endothelial cells, whereas it inhibited adipogenesis in vitro. In addition, we found that <span>l</span>-arginine altered the expression of PINK1/Parkin and Bnip3 in the mitochondria of osteoblast-lineage and endothelial cells, thereby promoting mitophagy and protecting cells from ROS. Similarly, <span>l</span>-arginine treatment effectively ameliorated osteoporosis in an ovariectomized mouse model.</p></div><div><h3>Conclusion</h3><p><span>l</span>-arginine promotes angio-osteogenesis, and inhibits adipogenesis, effects mediated by the PINK1/Parkin- and Bnip3-mediated mitophagy.</p></div><div><h3>The Translational Potential of this Article</h3><p>L-arginine supplementation may be an effective adjunct therapy in the treatment of osteoporosis.</p></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"46 ","pages":"Pages 53-64"},"PeriodicalIF":6.6,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214031X24000275/pdfft?md5=f778df8bd039a297ac9ffe9d86a22309&pid=1-s2.0-S2214031X24000275-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141073076","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":"Effects of physical exercise on neuromuscular junction degeneration during ageing: A systematic review","authors":"Qianjin Wang ,&nbsp;Can Cui ,&nbsp;Ning Zhang ,&nbsp;Wujian Lin ,&nbsp;Senlin Chai ,&nbsp;Simon Kwoon-Ho Chow ,&nbsp;Ronald Man Yeung Wong ,&nbsp;Yong Hu ,&nbsp;Sheung Wai Law ,&nbsp;Wing-Hoi Cheung","doi":"10.1016/j.jot.2024.03.007","DOIUrl":"https://doi.org/10.1016/j.jot.2024.03.007","url":null,"abstract":"<div><p>The neuromuscular junction (NMJ) is a specialized chemical synapse that converts neural impulses into muscle action. Age-associated NMJ degeneration, which involves nerve terminal and postsynaptic decline, denervation, and loss of motor units, significantly contributes to muscle weakness and dysfunction. Although physical training has been shown to make substantial modifications in NMJ of both young and aged animals, the results are often influenced by methodological variables in existing studies. Moreover, there is still lack of strong consensus on the specific effects of exercise on improving the morphology and function of the ageing NMJ. Consequently, the purpose of this study was to conduct a systematic review to elucidate the effects of exercise training on NMJ compartments in the elderly.</p><p>We conducted a systematic review using PubMed, Embase, and Web of Science databases, employing relevant keywords. Two independent reviewers selected studies that detailed NMJ changes during exercise in ageing, written in English, and available in full text.</p><p>In total, 20 papers were included. We examined the altered adaptation of the NMJ to exercise, focusing on presynaptic and postsynaptic structures and myofibers in older animals or humans. Our findings indicated that aged NMJs exhibited different adaptive responses to physical exercise compared to younger counterparts. Endurance training, compared with resistance and voluntary exercise regimens, was found to have a more pronounced effect on NMJ structural remodeling, particularly in fast twitch muscle fibers. Physical exercise was observed to promote the formation and maintenance of acetylcholine receptor (AChR) clusters by increasing the recombinant docking protein 7 (Dok7) expression and stabilizing Agrin and lipoprotein receptor-related protein 4 (LRP4). These insights suggest that research on exercise-related therapies could potentially attenuate the progression of neuromuscular degeneration.</p><p>Translational potential of this article: This systematic review provides a detailed overview of the effects of different types of physical exercise on improving NMJ in the elderly, providing scientific support for the timely intervention of muscle degeneration in the elderly by physical exercise, and providing help for the development of new therapeutic interventions in the future.</p></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"46 ","pages":"Pages 91-102"},"PeriodicalIF":6.6,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214031X2400038X/pdfft?md5=aca3649b019d26e1fcc498c32afe81ce&pid=1-s2.0-S2214031X2400038X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141083807","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":"HIF-2α/TFR1 mediated iron homeostasis disruption aggravates cartilage endplate degeneration through ferroptotic damage and mtDNA release: A new mechanism of intervertebral disc degeneration","authors":"Xingzhi Jing ,&nbsp;Wenchao Wang ,&nbsp;Xining He ,&nbsp;Xiaoyang Liu ,&nbsp;Xiaoxia Yang ,&nbsp;Cheng Su ,&nbsp;Yuandong Shao ,&nbsp;Zhongpeng Ge ,&nbsp;Heran Wang ,&nbsp;Xingang Cui","doi":"10.1016/j.jot.2024.03.005","DOIUrl":"https://doi.org/10.1016/j.jot.2024.03.005","url":null,"abstract":"<div><h3>Backgroud</h3><p>Iron overload is a prevalent condition in the elderly, often associated with various degenerative diseases, including intervertebral disc degeneration (IDD). Nevertheless, the mechanisms responsible for iron ion accumulation in tissues and the mechanism that regulate iron homeostasis remain unclear. Transferrin receptor-1 (TFR1) serves as the primary cellular iron gate, playing a pivotal role in controlling intracellular iron levels, however its involvement in IDD pathogenesis and the underlying mechanism remains obscure.</p></div><div><h3>Methods</h3><p>Firstly, IDD mice model was established to determine the iron metabolism associated proteins changes during IDD progression. Then CEP chondrocytes were isolated and treated with TBHP or pro-inflammatory cytokines to mimic pathological environment, western blotting, immunofluorescence assay and tissue staining were employed to explore the underlying mechanisms. Lastly, TfR1 siRNA and Feristatin II were employed and the degeneration of IDD was examined using micro-CT and immunohistochemical analysis.</p></div><div><h3>Results</h3><p>We found that the IDD pathological environment, characterized by oxidative stress and pro-inflammatory cytokines, could enhance iron influx by upregulating TFR1 expression in a HIF-2α dependent manner. Excessive iron accumulation not only induces chondrocytes ferroptosis and exacerbates oxidative stress, but also triggers the innate immune response mediated by c-GAS/STING, by promoting mitochondrial damage and the release of mtDNA. The inhibition of STING through siRNA or the reduction of mtDNA replication using ethidium bromide alleviated the degeneration of CEP chondrocytes induced by iron overload.</p></div><div><h3>Conclusion</h3><p>Our study systemically explored the role of TFR1 mediated iron homeostasis in IDD and its underlying mechanisms, implying that targeting TFR1 to maintain balanced iron homeostasis could offer a promising therapeutic approach for IDD management.</p></div><div><h3>The translational potential of this article</h3><p>Our study demonstrated the close link between iron metabolism dysfunction and IDD, indicated that targeting TfR1 may be a novel therapeutic strategy for IDD.</p></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"46 ","pages":"Pages 65-78"},"PeriodicalIF":6.6,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214031X24000305/pdfft?md5=f696ffc796d7be98460c6e42e3ab5f8d&pid=1-s2.0-S2214031X24000305-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141077742","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":"Smoking and osteoimmunology: Understanding the interplay between bone metabolism and immune homeostasis","authors":"Guangyang Xie ,&nbsp;Cheng Huang ,&nbsp;Shide Jiang ,&nbsp;Hengzhen Li ,&nbsp;Yihan Gao ,&nbsp;Tingwei Zhang ,&nbsp;Qidong Zhang ,&nbsp;Volotovski Pavel ,&nbsp;Masoud Rahmati ,&nbsp;Yusheng Li","doi":"10.1016/j.jot.2024.04.003","DOIUrl":"https://doi.org/10.1016/j.jot.2024.04.003","url":null,"abstract":"<div><p>Smoking continues to pose a global threat to morbidity and mortality in populations. The detrimental impact of smoking on health and disease includes bone destruction and immune disruption in various diseases. Osteoimmunology, which explores the communication between bone metabolism and immune homeostasis, aims to reveal the interaction between the osteoimmune systems in disease development. Smoking impairs the differentiation of mesenchymal stem cells and osteoblasts in bone formation while promoting osteoclast differentiation in bone resorption. Furthermore, smoking stimulates the Th17 response to increase inflammatory and osteoclastogenic cytokines that promote the receptor activator of NF-κB ligand (RANKL) signaling in osteoclasts, thus exacerbating bone destruction in periodontitis and rheumatoid arthritis. The pro-inflammatory role of smoking is also evident in delayed bone fracture healing and osteoarthritis development. The osteoimmunological therapies are promising in treating periodontitis and rheumatoid arthritis, but further research is still required to block the smoking-induced aggravation in these diseases.</p></div><div><h3>Translational potential</h3><p>This review summarizes the adverse effect of smoking on mesenchymal stem cells, osteoblasts, and osteoclasts and elucidates the smoking-induced exacerbation of periodontitis, rheumatoid arthritis, bone fracture healing, and osteoarthritis from an osteoimmune perspective. We also propose the therapeutic potential of osteoimmunological therapies for bone destruction aggravated by smoking.</p></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"46 ","pages":"Pages 33-45"},"PeriodicalIF":6.6,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214031X24000408/pdfft?md5=7dd412068790f6c6e18184d3ae4dd30b&pid=1-s2.0-S2214031X24000408-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140906543","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}