Journal of Orthopaedic Translation最新文献

{"title":"Human umbilical cord mesenchymal stem cell-derived exosomes ameliorate muscle atrophy via the miR-132-3p/FoxO3 axis","authors":"Huihui Ma , Yujie Jing , Jiangping Zeng , Jiaying Ge , Siqi Sun , Ran Cui , Chunhua Qian , Shen Qu , Hui Sheng","doi":"10.1016/j.jot.2024.08.005","DOIUrl":"10.1016/j.jot.2024.08.005","url":null,"abstract":"<div><h3>Background</h3><div>Muscle atrophy or sarcopenia is the loss of muscle mass and strength and leads to an increased risk of disability and death including osteoporotic fractures. Currently, there are no available clinical biologic agents for the treatment of sarcopenia. Since exosomes have become increasingly attractive as a novel therapeutic approach due to their ability to facilitate cell-cell transfer of proteins and RNAs, promoting cell repair and function recovery, we hypothesized that human umbilical cord mesenchymal stem cell-derived exosomes (hucMSC-Exos) might benefit muscle atrophy in age-related and dexamethasone-induced sarcopenia animal models.</div></div><div><h3>Methods</h3><div>HucMSC-Exos were harvested by ultrafast centrifugation and identified by transmission electron microscopy, particle size analysis, and Western blot analysis. The effects of hucMSC-Exos on muscle atrophy were evaluated using age-related and dexamethasone-induced muscle atrophy mice models. Body weight, grip strength, muscle weight, and muscle histology of these mice were assessed. The expression levels of muscle RING finger 1 (MuRF1) and muscle atrophy F-box (atrogin-1) were measured by Western blot. Dexamethasone-induced C2C12 myotube atrophy was used to establish the cell model of muscle atrophy. Myotube diameter was evaluated by immunofluorescence staining. Bioinformatic analysis, RNA sequencing analysis, and Western blot analysis were performed to explore the underlying mechanisms.</div></div><div><h3>Results</h3><div>In vivo experiments, hucMSC-Exos demonstrated a remarkable capacity to improve grip strength, increase muscle mass, and muscle fiber cross-sectional area, while concurrently reducing the expression of MuRF1 and atrogin-1 in age-related and dexamethasone-induced muscle atrophy mice. In vitro experiments, hucMSC-Exos can promote the proliferation of C2C12 cells, and rescue the dexamethasone-induced decline in the viability of C2C12 myotubes. In addition, hucMSC-Exos can increase the diameter of C2C12 myotubes, and reduce dexamethasone-induced upregulation of MuRF1 and atrogin-1. Combined with bioinformatics analysis and RNA sequencing analysis, we further showed that miR-132-3p was one of the essential miRNAs in hucMSC-Exos and played an important role by targeting FoxO3.</div></div><div><h3>Conclusion</h3><div>Our findings suggested that hucMSC-Exos can improve age-related and dexamethasone-induced muscle atrophy in mice models. This study first demonstrated that hucMSC-Exos may ameliorate muscle atrophy via the miR-132-3p/FoxO3 axis. These data may provide novel and valuable insights into the clinical transformation of hucMSC-Exos for the treatment of sarcopenia.</div></div><div><h3>The translational potential of this article</h3><div>HucMSC-Exos are easily available for clinical application, this study further consolidates the evidence for the clinical transformation potential of hucMSC-Exos for sarcopenia and provides its new targ","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"49 ","pages":"Pages 23-36"},"PeriodicalIF":5.9,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142421805","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":"Sustained BMP-2 delivery via alginate microbeads and polydopamine-coated 3D-Printed PCL/β-TCP scaffold enhances bone regeneration in long bone segmental defects","authors":"Seoyun Lee ,&nbsp;Jae-Hun Kim ,&nbsp;Yong-Hun Kim ,&nbsp;Jihyeock Hong ,&nbsp;Woo Keyoung Kim ,&nbsp;Songwan Jin ,&nbsp;Byung-Jae Kang","doi":"10.1016/j.jot.2024.08.013","DOIUrl":"10.1016/j.jot.2024.08.013","url":null,"abstract":"<div><h3>Background/Objective</h3><div>Repair of long bone defects remains a major challenge in clinical practice, necessitating the use of bone grafts, growth factors, and mechanical stability. Hence, a combination therapy involving a 3D-printed polycaprolactone (PCL)/β-tricalcium phosphate (β-TCP) scaffold coated with polydopamine (PDA) and alginate microbeads (AM) for sustained delivery of bone morphogenetic protein-2 (BMP-2) was investigated to treat long bone segmental defects.</div></div><div><h3>Methods</h3><div>Several in vitro analyses were performed to evaluate the scaffold osteogenic effects in vitro such as PDA surface modification, namely, hydrophilicity and cell adhesion; cytotoxicity and BMP-2 release kinetics using CCK-8 assay and ELISA, respectively; osteogenic differentiation in canine adipose-derived mesenchymal stem cells (Ad-MSCs); formation of mineralized nodules using ALP staining and ARS staining; and mRNA expression of osteogenic differentiation markers using RT-qPCR. Bone regeneration in femoral bone defects was evaluated in vivo using a rabbit femoral segmental bone defect model by performing radiography, micro-computed tomography, and histological observation (hematoxylin and eosin and Masson's trichrome staining).</div></div><div><h3>Results</h3><div>The PDA-coated 3D-printed scaffold demonstrated increased hydrophilicity, cell adhesion, and cell proliferation compared with that of the control. BMP-2 release kinetics assessment showed that BMP-2 AM showed a reduced initial burst and continuous release for 28 days. <em>In vitro</em> co-culture with canine Ad-MSCs showed an increase in mineralization and mRNA expression of osteogenic markers in the BMP-2 AM group compared with that of the BMP-2-adsorbed scaffold group. <em>In vivo</em> bone regeneration evaluation 12 weeks after surgery showed that the BMP-2 AM/PDA group exhibited the highest bone volume in the scaffold, followed by the BMP-2/PDA group. High cortical bone connectivity was observed in the PDA-coated scaffold groups.</div></div><div><h3>Conclusion</h3><div>These findings suggest that the combined use of PDA-coated 3D-printed bone scaffolds and BMP-2 AM can successfully induce bone regeneration even in load-bearing bone segmental defects.</div></div><div><h3>The translational potential of this article</h3><div>A 3D-printed PCL/β-TCP scaffold was fabricated to mimic the cortical bone of the femur. Along with the application of PDA surface modification and sustained BMP-2 release via AM, the developed scaffold could provide suitable osteoconduction, osteoinduction, and osteogenesis in both in vitro settings and in vivo rabbit femoral segmental bone defect models. Therefore, our findings suggest a promising therapeutic option for treating challenging long bone segmental defects, with potential for future clinical application.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"49 ","pages":"Pages 11-22"},"PeriodicalIF":5.9,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142421804","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":"Failure analysis and design improvement of retrieved plates from revision surgery","authors":"Ning-Ze Zhang ,&nbsp;Yang-Yang Shui ,&nbsp;Qi-Da Zhang ,&nbsp;Yuan-Tao Zhang ,&nbsp;Jian Su ,&nbsp;Ling Qin ,&nbsp;Cheng-Kung Cheng","doi":"10.1016/j.jot.2024.08.011","DOIUrl":"10.1016/j.jot.2024.08.011","url":null,"abstract":"<div><h3>Background</h3><div>The fracture of bone plate can cause considerable pain for the patient and increase the burden on the public finances. This study aims to explore the failure mechanism of 49 plates retrieved from revision surgery and introduce pure magnesium (Mg) block to improve the biomechanical performance of the plate via decreasing the stiffness and to stimulate the biological response of the plate potentially by the degradation of Mg block.</div></div><div><h3>Methods</h3><div>The morphological analysis and component analysis of the plates were conducted to determine the fracture reason of the plates combining the clinical data. According to the structural feature, the 49 retrieved plates were divided into: traditional plate (TP), asymmetrical plate (AP), reconstructive plate (RP) and central enhancement plate (CEP), and their structure features are normalized in a commercial plate, respectively. The biomechanical performance of the plates was evaluated using a validated femoral finite element model. A block of pure Mg with a thickness of 1 mm, 1.5 mm and 2 mm was also incorporated into the CEP to be assessed.</div></div><div><h3>Results</h3><div>The results indicated that the retrieved plates mainly failed due to fatigue fracture induced by delayed union or nonunion (44/49), and using pure titanium plates in weight-bearing areas increased the risk of fracture compared with Ti alloy plates when the delayed union or nonunion occurred. The TP demonstrated the highest compression resistance and bending resistance, while CEP had the highest rotational resistance. As the thickness of the Mg block was increased, the stress on the plate in compression decreased, but the stress in rotation increased. The plate with a 1.5 mm Mg block demonstrated excellent compression resistance, bending resistance and rotational resistance.</div></div><div><h3>Conclusion</h3><div>Fatigue fracture resulting from the delayed union or nonunion is the primary failure reason of plates in clinic. The incorporation of Mg block into plate improves the biomechanical performance and has the potential to promote bone healing. The plate with a 1.5 mm Mg block may be suitable for use in orthopaedics.</div></div><div><h3>The translational potential of this article</h3><div>This study assessed the failure mechanism of retrieved bone plates and used this data to develop a novel plate incorporating a 1.5 mm block of pure Mg block at the position corresponding to the fracture line. The novel plate exhibited excellent compression resistance, bending resistance and rotational resistance due to the alleviation of stress concentrations. The Mg block has the potential to degrade over time to promote fracture healing and prevents fatigue fracture of plates.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"49 ","pages":"Pages 1-10"},"PeriodicalIF":5.9,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142327734","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":"FOXO1-mTOR pathway in vascular pericyte regulates the formation of type H vessels to control bone metabolism","authors":"Caiyu Cheng ,&nbsp;Mingye Deng ,&nbsp;Chubin Cheng ,&nbsp;Hangtian Wu ,&nbsp;Yutian Wang ,&nbsp;Mincheng Lu ,&nbsp;Zilong Yao ,&nbsp;Kaiqun Li ,&nbsp;Xianrong Zhang ,&nbsp;Bin Yu","doi":"10.1016/j.jot.2024.08.010","DOIUrl":"10.1016/j.jot.2024.08.010","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;As the population aging progresses, age-related osteoporosis has become one of the most common and severe chronic degenerative diseases. Due to insufficient understanding of its complex pathomechanisms, current clinical treatments often suffer from many negative effects. Type H vessels play critical role in bone remodeling owing to their specialized function in coupling angiogenesis and osteogenesis. Increasing evidences have shown a close association between the age-related decline of type H vessels and bone loss. However, the underlying mechanisms whereby the regression of type H vessels with aging remain largely unknown.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;&lt;em&gt;Col2-Cre&lt;/em&gt;&lt;sup&gt;&lt;em&gt;ERT&lt;/em&gt;&lt;/sup&gt;&lt;em&gt;/Foxo1&lt;/em&gt;&lt;sup&gt;&lt;em&gt;flox/flox&lt;/em&gt;&lt;/sup&gt; mice and FOXO1 inhibitor (AS1842856) treated adult (6 months) and middle aged (10 months) mice were utilized for evaluating the variations in bone volume, bone microarchitecture and type H vessels through micro-CT scanning analysis, histological staining and immunofluorescence staining. &lt;em&gt;In vitro&lt;/em&gt; tube-forming and scratch assays were applied to evaluate the angiogenic capacity of human umbilical vein endothelial cells (HUVECs) exposed to AS1842856 or conditioned culture milieu of Human Brain Vascular Pericytes (HBVPs). The expression of pericyte marker proteins, myofibroblast-related proteins and genes in inhibitors-stimulated HBVPs were detected via western blot analysis and Reverse transcription-quantitative PCR (RT-qPCR). Furthermore, perivascular myofibroblastic-like transformation was confirmed in AS1842856-treated animal models through immunofluorescence staining. We also constructed &lt;em&gt;Adipoq-Cre/Foxo1&lt;/em&gt;&lt;sup&gt;&lt;em&gt;flox/flox&lt;/em&gt;&lt;/sup&gt; conditional knockout mice and measured their bone mass and type H vessels by micro-CT and immunofluorescence staining. Mechanistic experiments &lt;em&gt;in vitro&lt;/em&gt; were conducted via detection of mTOR signalling expression in HBVPs with pharmacological intervention (AS1842856 and rapamycin), genetic knockdown of &lt;em&gt;Foxo1&lt;/em&gt;, or FOXO1-overexpression plasmid treatment, verified by RT-qPCR, western blot analysis and cellular immunofluorescence staining. &lt;em&gt;In vivo&lt;/em&gt; validation was conducted on &lt;em&gt;Adipoq-Cre/Foxo1&lt;/em&gt;&lt;sup&gt;&lt;em&gt;flox/flox&lt;/em&gt;&lt;/sup&gt; mice using immunofluorescence staining. Finally, alterations in osteo-morphology and type H vessels were verified in AS1842856-treated and rapamycin-treated aged mouse models.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;This study identified FOXO1 in pericytes as key components for the formation of type H vessels. We found that FOXO1 expression in pericytes decreases with aging, and pharmacological blocking with AS1842856 promoted type H vessels degeneration and increased bone loss in adult and middle-aged mice, while rapamycin prevented the above pathology in middle-aged mice. We further showed that the loss of FOXO1 in &lt;em&gt;Adipoq&lt;/em&gt;&lt;sup&gt;+&lt;/sup&gt; pericytes led to degeneration of type H vessels","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"49 ","pages":"Pages 246-263"},"PeriodicalIF":5.9,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142526266","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":"Emerging role of liver-bone axis in osteoporosis","authors":"Hongliang Gao ,&nbsp;Xing Peng ,&nbsp;Ning Li ,&nbsp;Liming Gou ,&nbsp;Tao Xu ,&nbsp;Yuqi Wang ,&nbsp;Jian Qin ,&nbsp;Hui Liang ,&nbsp;Peiqi Ma ,&nbsp;Shu Li ,&nbsp;Jing Wu ,&nbsp;Xihu Qin ,&nbsp;Bin Xue","doi":"10.1016/j.jot.2024.07.008","DOIUrl":"10.1016/j.jot.2024.07.008","url":null,"abstract":"<div><h3>Background</h3><p>Increasing attention to liver-bone crosstalk has spurred interest in targeted interventions for various forms of osteoporosis. Liver injury induced by different liver diseases can cause an imbalance in bone metabolism, indicating a novel regulatory paradigm between the liver and bone. However, the role of the liver-bone axis in both primary and secondary osteoporosis remains inadequately elucidated. Therefore, exploring the exact regulatory mechanisms of the liver-bone axis may offer innovative clinical approaches for treating diseases associated with the liver and bone.</p></div><div><h3>Methods</h3><p>Here, we summarize the latest research on the liver-bone axis by searching the PubMed and Web of Science databases and discuss the possible mechanism of the liver-bone axis in different types of osteoporosis. The literature directly reporting the regulatory role of the liver-bone axis in different types of osteoporosis from the PubMed and Web of Science databases has been included in the discussion of this review (including but not limited to the definition of the liver-bone axis, clinical studies, and basic research). In addition, articles discussing changes in bone metabolism caused by different etiologies of liver injury have also been included in the discussion of this review (including but not limited to clinical studies and basic research).</p></div><div><h3>Results</h3><p>Several endocrine factors (IGF-1, FGF21, hepcidin, vitamin D, osteocalcin, OPN, LCAT, Fetuin-A, PGs, BMP2/9, IL-1/6/17, and TNF-α) and key genes (SIRT2, ABCB4, ALDH2, TFR2, SPTBN1, ZNF687 and SREBP2) might be involved in the regulation of the liver-bone axis. In addition to the classic metabolic pathways involved in inflammation and oxidative stress, iron metabolism, cholesterol metabolism, lipid metabolism and immunometabolism mediated by the liver-bone axis require more research to elucidate the regulatory mechanisms involved in osteoporosis.</p></div><div><h3>Conclusion</h3><p>During primary and secondary osteoporosis, the liver-bone axis is responsible for liver and bone homeostasis via several hepatokines and osteokines as well as biochemical signaling. Combining multiomics technology and data mining technology could further advance our understanding of the liver-bone axis, providing new clinical strategies for managing liver and bone-related diseases.</p><p><strong>The translational potential of this article</strong> is as follows: Abnormal metabolism in the liver could seriously affect the metabolic imbalance of bone. This review summarizes the indispensable role of several endocrine factors and biochemical signaling pathways involved in the liver-bone axis and emphasizes the important role of liver metabolic homeostasis in the pathogenesis of osteoporosis, which provides novel potential directions for the prevention, diagnosis, and treatment of liver and bone-related diseases.</p></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"48 ","pages":"Pages 217-231"},"PeriodicalIF":5.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214031X24000767/pdfft?md5=81f2e7a9c2b6b979ad8cbbfc8d695bf8&pid=1-s2.0-S2214031X24000767-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142136530","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":"Biomarkers for hypertrophic chondrocyte differentiation are associated with spatial cellular organisation and suggest endochondral ossification-like processes in osteoarthritic cartilage: An exploratory study","authors":"Julius Michael Wolfgart ,&nbsp;Lea Cathrine Grötzner ,&nbsp;Sascha Hemayatkar-Fink ,&nbsp;Maik Schwitalle ,&nbsp;Florian Christof Bonnaire ,&nbsp;Martina Feierabend ,&nbsp;Marina Danalache ,&nbsp;Ulf Krister Hofmann","doi":"10.1016/j.jot.2024.08.006","DOIUrl":"10.1016/j.jot.2024.08.006","url":null,"abstract":"<div><h3>Background</h3><p>In healthy articular cartilage, chondrocytes are found along arcades of collagen fibers as Single Strings. With onset of cartilage degeneration this pattern changes to Double Strings. In the course of osteoarthritis Small Clusters, and finally Big Clusters form. In highly degenerated articular cartilage, another poorly understood pattern is found where chondrocyte morphology differs considerably, and the distribution of cells is diffuse. Progression of osteoarthritis is accompanied by key processes such as chondrocyte proliferation, apoptosis, hypertrophic differentiation, inflammation, and angiogenesis. The aim of this exploratory study was to identify biomarkers for these processes in the context of spatial cellular organizational changes in articular cartilage.</p></div><div><h3>Methods</h3><p>Cartilage explants (n = 166 patients) were sorted according to their predominant cellular pattern. Quantitative or semi-quantitative analysis of 39 biomarkers were performed by multiplex assay (31) or ELISA (8), and qualitative analysis on 12 immunohistochemical markers.</p></div><div><h3>Results</h3><p>Hypertrophic differentiation (e.g. type-X collagen, osteopontin, osteocalcin and interleukin-6) and angiogenesis were associated with changes in chondrocyte organisation. First changes take place already at the transition from Single Strings to Double Strings. Drastic changes in the appearance of numerous biomarkers are found at the transition from Big Clusters to Diffuse.</p></div><div><h3>Conclusion</h3><p>Key processes in osteoarthritis and their biomarkers seem to depend on the spatial distribution of chondrocytes in articular cartilage. Abrupt changes in biomarker occurrence were observed between Big Clusters and Diffuse insinuating that the Diffuse pattern is composed of a different cell population or at least a different form of chondrocyte morphology.</p></div><div><h3>The Translational Potential of this Article</h3><p>In situ identification of the different spatial chondrocyte patterns by fluorescence microscopy has already been established in the recent past. Analysing human in-situ cartilage explants rather than isolated OA chondrocytes closes the gap between in vitro and in vivo studies and as such, stretches a big step towards translation of the observed findings. The direct association between tissue biomarker profile and cellular arrangements representing different states of OA sheds new light on the molecular and cellular physiopathology, especially in the context of larger processes such as angiogenesis, cellular proliferation, differentiation, and apoptosis. This also opens an interesting perspective for future investigation of such biomarkers and processes in clinical studies.</p></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"48 ","pages":"Pages 232-243"},"PeriodicalIF":5.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214031X24000937/pdfft?md5=2300829e74c4b5b2ff19c1bba55a0590&pid=1-s2.0-S2214031X24000937-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142229907","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":"Corrigendum to ‘JD-312 – A novel small molecule that facilitates cartilage repair and alleviates osteoarthritis progression’[Journal of Orthopaedic Translation 44 (2024) 60–71]","authors":"Jingduo Gao ,&nbsp;Haixiang Pei ,&nbsp;Fang Lv ,&nbsp;Xin Niu ,&nbsp;Yu You ,&nbsp;Liang He ,&nbsp;Shijia Hu ,&nbsp;Karan M. Shah ,&nbsp;Mingyao Liu ,&nbsp;Yihua Chen ,&nbsp;Bing Du ,&nbsp;Hai Xiong ,&nbsp;Jian Luo","doi":"10.1016/j.jot.2024.08.017","DOIUrl":"10.1016/j.jot.2024.08.017","url":null,"abstract":"","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"48 ","pages":"Pages 244-246"},"PeriodicalIF":5.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214031X24001049/pdfft?md5=f2fe10427d493a4bb5c7e32136af2778&pid=1-s2.0-S2214031X24001049-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142310294","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":"Corrigendum to “Sirt1 protects against intervertebral disc degeneration induced by 1,25-Dihydroxyvitamin D insufficiency in mice by inhibiting the NF-κB inflammatory pathway”[Journal of Orthopaedic Translation 40 (2023) 13–26]","authors":"Peng Wang ,&nbsp;Cuicui Yang ,&nbsp;Jinhong Lu ,&nbsp;Yongxin Ren ,&nbsp;David Goltzman ,&nbsp;Dengshun Miao","doi":"10.1016/j.jot.2024.08.019","DOIUrl":"10.1016/j.jot.2024.08.019","url":null,"abstract":"","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"48 ","pages":"Pages 247-253"},"PeriodicalIF":5.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214031X24001062/pdfft?md5=25ef67a88727873a459e713e0a3e0239&pid=1-s2.0-S2214031X24001062-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142310291","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":"Addressing musculoskeletal disorders through new treatment strategies","authors":"Heng Sun,&nbsp;Bin Li,&nbsp;Huilin Yang","doi":"10.1016/j.jot.2024.09.001","DOIUrl":"10.1016/j.jot.2024.09.001","url":null,"abstract":"","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"48 ","pages":"Pages A1-A2"},"PeriodicalIF":5.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214031X24001128/pdfft?md5=95072c3fc6fa7f1148f91c5afd092014&pid=1-s2.0-S2214031X24001128-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142310293","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":"METTL14-mediated HOXA5 m6A modification alleviates osteoporosis via promoting WNK1 transcription to suppress NLRP3-dependent macrophage pyroptosis","authors":"Hao Tang ,&nbsp;Yuxuan Du ,&nbsp;Zejiu Tan ,&nbsp;Dongpeng Li ,&nbsp;Jiang Xie","doi":"10.1016/j.jot.2024.08.008","DOIUrl":"10.1016/j.jot.2024.08.008","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;p&gt;Osteoporosis is a commonly diagnosed metabolic bone disease. NLRP3 inflammasome activation and pyroptosis are observed during osteoporosis. However, the mechanism by which NLRP3-mediated pyroptosis contributes to osteoporosis remains largely undefined.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;p&gt;Ovariectomized (OVX) mice were employed as an &lt;em&gt;in vivo&lt;/em&gt; model of osteoclastogenesis. H&amp;E staining and micro-CT detected the histological changes and bone parameters in the femur tissues. RANKL-treated macrophages were used as the &lt;em&gt;in vitro&lt;/em&gt; model of osteoclastogenesis, and LPS/ATP treatment was used as the macrophage pyroptosis model. The cytotoxicity, cytokine secretion and caspase-1 activity were assessed by LDH release assay, ELISA and flow cytometry, respectively. The osteoclast formation ability was detected by TRAP staining. qRT-PCR, IHC and Western blotting detected the expression and localization of METTL14, pyroptosis-related or osteoclast-specific molecules in femur tissues or macrophages. Mechanistically, MeRIP assessed the m&lt;sup&gt;6&lt;/sup&gt;A modification of &lt;em&gt;HOXA5&lt;/em&gt;. Luciferase and ChIP assays were employed to detect the direct association between HOXA5 and &lt;em&gt;WNK1&lt;/em&gt; promoter in macrophages.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;p&gt;METTL14, HOXA5 and WNK1 were decreased in OVX mice, which was associated with pyroptosis. METTL14 or HOXA5 overexpression suppressed macrophage-osteoclast differentiation and pyroptosis, along with the upregulation of WNK1. METTL14-mediated m&lt;sup&gt;6&lt;/sup&gt;A modification stabilized &lt;em&gt;HOXA5&lt;/em&gt; mRNA and increased its expression, and HOXA5 regulated &lt;em&gt;WNK1&lt;/em&gt; expression via direct binding to its promoter. Functional studies showed that WNK1 knockdown counteracted METTL14- or HOXA5-suppressed pyroptosis and macrophage-osteoclast differentiation. In OVX mice, overexpression of METTL14 or HOXA5 alleviated osteoporosis via suppressing WNK1-dependent NLRP3 signaling.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;p&gt;METTL14-mediated &lt;em&gt;HOXA5&lt;/em&gt; m&lt;sup&gt;6&lt;/sup&gt;A modification increased its expression, thereby inducing &lt;em&gt;WNK1&lt;/em&gt; expression and suppressing NLRP3-dependent pyroptosis to alleviate osteoporosis. The combination of METTL14 or HOXA5 agonist with pyroptosis targeted therapy may be a promising therapeutic approach for osteoporosis.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;The Translational Potential of this Article·&lt;/h3&gt;&lt;p&gt;&lt;/p&gt;&lt;ul&gt;&lt;li&gt;&lt;span&gt;•&lt;/span&gt;&lt;span&gt;&lt;p&gt;METTL14 or HOXA5 overexpression suppressed macrophage-osteoclast differentiation and pyroptosis in macrophages.·&lt;/p&gt;&lt;/span&gt;&lt;/li&gt;&lt;li&gt;&lt;span&gt;•&lt;/span&gt;&lt;span&gt;&lt;p&gt;METTL14-mediated m6A modification stabilized HOXA5 mRNA and increased its expression.&lt;/p&gt;&lt;/span&gt;&lt;/li&gt;&lt;li&gt;&lt;span&gt;•&lt;/span&gt;&lt;span&gt;&lt;p&gt;HOXA5 regulated WNK1 expression via direct binding to its promoter.&lt;/p&gt;&lt;/span&gt;&lt;/li&gt;&lt;li&gt;&lt;span&gt;•&lt;/span&gt;&lt;span&gt;&lt;p&gt;Silencing of WNK1 reversed METTL14- or HOXA5-suppressed pyroptosis and macrophageosteoclast differentiation.·&lt;/p&gt;&lt;/span&gt;&lt;/li&gt;&lt;li&gt;&lt;span&gt;•&lt;/span&gt;&lt;span&gt;&lt;p&gt;METTL14 or HOXA5 over","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"48 ","pages":"Pages 190-203"},"PeriodicalIF":5.9,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214031X24000950/pdfft?md5=7eb5c8164c8519c68ffa80f040877e93&pid=1-s2.0-S2214031X24000950-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142076678","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}