Bone & Joint Research最新文献

{"title":"siRNA incorporated in slow-release injectable hydrogel continuously silences DDIT4 and regulates nucleus pulposus cell pyroptosis through the ROS/TXNIP/NLRP3 axis to alleviate intervertebral disc degeneration.","authors":"Miao Ma, Chongjing Zhang, Zeyuan Zhong, Yajun Wang, Xuegang He, Daxue Zhu, Zhi Qian, Baoqing Yu, Xuewen Kang","doi":"10.1302/2046-3758.135.BJR-2023-0320.R1","DOIUrl":"10.1302/2046-3758.135.BJR-2023-0320.R1","url":null,"abstract":"<p><strong>Aims: </strong>In this investigation, we administered oxidative stress to nucleus pulposus cells (NPCs), recognized DNA-damage-inducible transcript 4 (DDIT4) as a component in intervertebral disc degeneration (IVDD), and devised a hydrogel capable of conveying small interfering RNA (siRNA) to IVDD.</p><p><strong>Methods: </strong>An in vitro model for oxidative stress-induced injury in NPCs was developed to elucidate the mechanisms underlying the upregulation of DDIT4 expression, activation of the reactive oxygen species (ROS)-thioredoxin-interacting protein (TXNIP)-NLRP3 signalling pathway, and nucleus pulposus pyroptosis. Furthermore, the mechanism of action of small interfering DDIT4 (siDDIT4) on NPCs in vitro was validated. A triplex hydrogel named siDDIT4@G5-P-HA was created by adsorbing siDDIT4 onto fifth-generation polyamidoamine (PAMAM) dendrimer using van der Waals interactions, and then coating it with hyaluronic acid (HA). In addition, we established a rat puncture IVDD model to decipher the hydrogel's mechanism in IVDD.</p><p><strong>Results: </strong>A correlation between DDIT4 expression levels and disc degeneration was shown with human nucleus pulposus and needle-punctured rat disc specimens. We confirmed that DDIT4 was responsible for activating the ROS-TXNIP-NLRP3 axis during oxidative stress-induced pyroptosis in rat nucleus pulposus in vitro. Mitochondria were damaged during oxidative stress, and DDIT4 contributed to mitochondrial damage and ROS production. In addition, siDDIT4@G5-P-HA hydrogels showed good delivery activity of siDDIT4 to NPCs. In vitro studies illustrated the potential of the siDDIT4@G5-P-HA hydrogel for alleviating IVDD in rats.</p><p><strong>Conclusion: </strong>DDIT4 is a key player in mediating pyroptosis and IVDD in NPCs through the ROS-TXNIP-NLRP3 axis. Additionally, siDDIT4@G5-P-HA hydrogel has been found to relieve IVDD in rats. Our research offers an innovative treatment option for IVDD.</p>","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"13 5","pages":"247-260"},"PeriodicalIF":4.7,"publicationDate":"2024-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11107476/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141070519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of cell-specific epigenetic patterns associated with chondroitin sulfate treatment response in an endemic arthritis, Kashin-Beck disease.","authors":"Bolun Cheng, Cuiyan Wu, Wenming Wei, Hui Niu, Yan Wen, Cheng Li, Ping Chen, Hong Chang, Zhengjun Yang, Feng Zhang","doi":"10.1302/2046-3758.135.BJR-2023-0271.R1","DOIUrl":"10.1302/2046-3758.135.BJR-2023-0271.R1","url":null,"abstract":"<p><strong>Aims: </strong>To assess the alterations in cell-specific DNA methylation associated with chondroitin sulphate response using peripheral blood collected from Kashin-Beck disease (KBD) patients before initiation of chondroitin sulphate treatment.</p><p><strong>Methods: </strong>Peripheral blood samples were collected from KBD patients at baseline of chondroitin sulphate treatment. Methylation profiles were generated using reduced representation bisulphite sequencing (RRBS) from peripheral blood. Differentially methylated regions (DMRs) were identified using MethylKit, while DMR-related genes were defined as those annotated to the gene body or 2.2-kilobase upstream regions of DMRs. Selected DMR-related genes were further validated by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) to assess expression levels. Tensor composition analysis was performed to identify cell-specific differential DNA methylation from bulk tissue.</p><p><strong>Results: </strong>This study revealed 21,060 hypermethylated and 44,472 hypomethylated DMRs, and 13,194 hypermethylated and 22,448 hypomethylated CpG islands for differential global methylation for chondroitin sulphate treatment response. A total of 12,666 DMR-related genes containing DMRs were identified in their promoter regions, such as <i>CHL1</i> (false discovery rate (FDR) = 2.11 × 10^-11), <i>RIC8A</i> (FDR = 7.05 × 10^-4), and <i>SOX12</i> (FDR = 1.43 × 10^-3). Additionally, <i>RIC8A</i> and <i>CHL1</i> were hypermethylated in responders, while <i>SOX12</i> was hypomethylated in responders, all showing decreased gene expression. The patterns of cell-specific differential global methylation associated with chondroitin sulphate response were observed. Specifically, we found that DMRs located in <i>TESPA1</i> and <i>ATP11A</i> exhibited differential DNA methylation between responders and non-responders in granulocytes, monocytes, and B cells.</p><p><strong>Conclusion: </strong>Our study identified cell-specific changes in DNA methylation associated with chondroitin sulphate response in KBD patients.</p>","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"13 5","pages":"237-246"},"PeriodicalIF":4.7,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11098597/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140956092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stable polyethylene inlay fixation and low polyethylene wear rate in fixed-bearing total knee arthroplasty at five to six years' follow-up.","authors":"Jonathan H Jürgens-Lahnstein, Emil T Petersen, Søren Rytter, Frank Madsen, Kjeld Søballe, Maiken Stilling","doi":"10.1302/2046-3758.135.BJR-2023-0126.R1","DOIUrl":"10.1302/2046-3758.135.BJR-2023-0126.R1","url":null,"abstract":"<p><strong>Aims: </strong>Micromotion of the polyethylene (PE) inlay may contribute to backside PE wear in addition to articulate wear of total knee arthroplasty (TKA). Using radiostereometric analysis (RSA) with tantalum beads in the PE inlay, we evaluated PE micromotion and its relationship to PE wear.</p><p><strong>Methods: </strong>A total of 23 patients with a mean age of 83 years (77 to 91), were available from a RSA study on cemented TKA with Maxim tibial components (Zimmer Biomet). PE inlay migration, PE wear, tibial component migration, and the anatomical knee axis were evaluated on weightbearing stereoradiographs. PE inlay wear was measured as the deepest penetration of the femoral component into the PE inlay.</p><p><strong>Results: </strong>At mean six years' follow-up, the PE wear rate was 0.08 mm/year (95% confidence interval 0.06 to 0.09 mm/year). PE inlay external rotation was below the precision limit and did not influence PE wear. Varus knee alignment did not influence PE wear (p = 0.874), but increased tibial component total translation (p = 0.041).</p><p><strong>Conclusion: </strong>The PE inlay was well fixed and there was no relationship between PE stability and PE wear. The PE wear rate was low and similar in the medial and lateral compartments. Varus knee alignment did not influence PE wear.</p>","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"13 5","pages":"226-236"},"PeriodicalIF":4.7,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11090217/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140891048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fracture haematoma proteomics.","authors":"Rald V M Groven, Christel Kuik, Johannes Greven, Ümit Mert, Freek G Bouwman, Martijn Poeze, Taco J Blokhuis, Markus Huber-Lang, Frank Hildebrand, Berta Cillero-Pastor, Martijn van Griensven","doi":"10.1302/2046-3758.135.bjr-2023-0323.r1","DOIUrl":"https://doi.org/10.1302/2046-3758.135.bjr-2023-0323.r1","url":null,"abstract":"The aim of this study was to determine the fracture haematoma (fxH) proteome after multiple trauma using label-free proteomics, comparing two different fracture treatment strategies.","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"226 1","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140835347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic factors associated with failure of total elbow arthroplasty.","authors":"Zaid Hamoodi, Celina K Gehringer, Lucy M Bull, Tom Hughes, Lianne Kearsley-Fleet, Jamie C Sergeant, Adam C Watts","doi":"10.1302/2046-3758.135.BJR-2023-0281.R1","DOIUrl":"10.1302/2046-3758.135.BJR-2023-0281.R1","url":null,"abstract":"<p><strong>Aims: </strong>The aims of this study were to identify and evaluate the current literature examining the prognostic factors which are associated with failure of total elbow arthroplasty (TEA).</p><p><strong>Methods: </strong>Electronic literature searches were conducted using MEDLINE, Embase, PubMed, and Cochrane. All studies reporting prognostic estimates for factors associated with the revision of a primary TEA were included. The risk of bias was assessed using the Quality In Prognosis Studies (QUIPS) tool, and the quality of evidence was assessed using the modified Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework. Due to low quality of the evidence and the heterogeneous nature of the studies, a narrative synthesis was used.</p><p><strong>Results: </strong>A total of 19 studies met the inclusion criteria, investigating 28 possible prognostic factors. Most QUIPS domains (84%) were rated as moderate to high risk of bias. The quality of the evidence was low or very low for all prognostic factors. In low-quality evidence, prognostic factors with consistent associations with failure of TEA in more than one study were: the sequelae of trauma leading to TEA, either independently or combined with acute trauma, and male sex. Several other studies investigating sex reported no association. The evidence for other factors was of very low quality and mostly involved exploratory studies.</p><p><strong>Conclusion: </strong>The current evidence investigating the prognostic factors associated with failure of TEA is of low or very low quality, and studies generally have a moderate to high risk of bias. Prognostic factors are subject to uncertainty, should be interpreted with caution, and are of little clinical value. Higher-quality evidence is required to determine robust prognostic factors for failure of TEA.</p>","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"13 5","pages":"201-213"},"PeriodicalIF":4.7,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11060869/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140847345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HDACi vorinostat protects muscle from degeneration after acute rotator cuff injury in mice.","authors":"Lara Gil-Melgosa, Rafael Llombart-Blanco, Leire Extramiana, Isabel Lacave, Gloria Abizanda, Estibaliz Miranda, Xabier Agirre, Felipe Prósper, Antonio Pineda-Lucena, Juan Pons-Villanueva, Ana Pérez-Ruiz","doi":"10.1302/2046-3758.134.bjr-2023-0292.r1","DOIUrl":"https://doi.org/10.1302/2046-3758.134.bjr-2023-0292.r1","url":null,"abstract":"Rotator cuff (RC) injuries are characterized by tendon rupture, muscle atrophy, retraction, and fatty infiltration, which increase injury severity and jeopardize adequate tendon repair. Epigenetic drugs, such as histone deacetylase inhibitors (HDACis), possess the capacity to redefine the molecular signature of cells, and they may have the potential to inhibit the transformation of the fibro-adipogenic progenitors (FAPs) within the skeletal muscle into adipocyte-like cells, concurrently enhancing the myogenic potential of the satellite cells.","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"17 1","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140595790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Repurposing the diuretic benzamil as an anti-osteosarcoma agent that acts by suppressing integrin/FAK/STAT3 signalling and compromising mitochondrial function.","authors":"Meng-Chieh Lin, Guan-Yu Chen, Hsin-Hsien Yu, Pei-Ling Hsu, Chu-Wan Lee, Chih-Cheng Cheng, Shih-Ying Wu, Bo-Syong Pan, Bor-Chyuan Su","doi":"10.1302/2046-3758.134.bjr-2023-0289.r1","DOIUrl":"https://doi.org/10.1302/2046-3758.134.bjr-2023-0289.r1","url":null,"abstract":"Osteosarcoma is the most common primary bone malignancy among children and adolescents. We investigated whether benzamil, an amiloride analogue and sodium-calcium exchange blocker, may exhibit therapeutic potential for osteosarcoma in vitro.","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"68 1","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140595615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mild aseptic lymphocyte-dominated vasculitis-associated lesion (ALVAL)-type reactions also present in patients with failed knee prostheses.","authors":"Anni Rajamäki, Lari Lehtovirta, Mika Niemeläinen, Aleksi Reito, Jyrki Parkkinen, Sirpa Peräniemi, Jouko Vepsäläinen, Antti Eskelinen","doi":"10.1302/2046-3758.134.bjr-2023-0255.r1","DOIUrl":"https://doi.org/10.1302/2046-3758.134.bjr-2023-0255.r1","url":null,"abstract":"Metal particles detached from metal-on-metal hip prostheses (MoM-THA) have been shown to cause inflammation and destruction of tissues. To further explore this, we investigated the histopathology (aseptic lymphocyte-dominated vasculitis-associated lesions (ALVAL) score) and metal concentrations of the periprosthetic tissues obtained from patients who underwent revision knee arthroplasty. We also aimed to investigate whether accumulated metal debris was associated with ALVAL-type reactions in the synovium.","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"49 1","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140595791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PEDF peptide plus hyaluronic acid stimulates cartilage regeneration in osteoarthritis via STAT3-mediated chondrogenesis.","authors":"Yung-Chang Lu, Tsung-Chuan Ho, Chang-Hung Huang, Shu-I Yeh, Show-Li Chen, Yeou-Ping Tsao","doi":"10.1302/2046-3758.134.BJR-2023-0179.R2","DOIUrl":"10.1302/2046-3758.134.BJR-2023-0179.R2","url":null,"abstract":"<p><strong>Aims: </strong>Pigment epithelium-derived factor (PEDF) is known to induce several types of tissue regeneration by activating tissue-specific stem cells. Here, we investigated the therapeutic potential of PEDF 29-mer peptide in the damaged articular cartilage (AC) in rat osteoarthritis (OA).</p><p><strong>Methods: </strong>Mesenchymal stem/stromal cells (MSCs) were isolated from rat bone marrow (BM) and used to evaluate the impact of 29-mer on chondrogenic differentiation of BM-MSCs in culture. Knee OA was induced in rats by a single intra-articular injection of monosodium iodoacetate (MIA) in the right knees (set to day 0). The 29-mer dissolved in 5% hyaluronic acid (HA) was intra-articularly injected into right knees at day 8 and 12 after MIA injection. Subsequently, the therapeutic effect of the 29-mer/HA on OA was evaluated by the Osteoarthritis Research Society International (OARSI) histopathological scoring system and changes in hind paw weight distribution, respectively. The regeneration of chondrocytes in damaged AC was detected by dual-immunostaining of 5-bromo-2'-deoxyuridine (BrdU) and chondrogenic markers.</p><p><strong>Results: </strong>The 29-mer promoted expansion and chondrogenic differentiation of BM-MSCs cultured in different defined media. MIA injection caused chondrocyte death throughout the AC, with cartilage degeneration thereafter. The 29-mer/HA treatment induced extensive chondrocyte regeneration in the damaged AC and suppressed MIA-induced synovitis, accompanied by the recovery of cartilage matrix. Pharmacological inhibitors of PEDF receptor (PEDFR) and signal transducer and activator of transcription 3 (STAT3) signalling substantially blocked the chondrogenic promoting activity of 29-mer on the cultured BM-MSCs and injured AC.</p><p><strong>Conclusion: </strong>The 29-mer/HA formulation effectively induces chondrocyte regeneration and formation of cartilage matrix in the damaged AC.</p>","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"13 4","pages":"137-148"},"PeriodicalIF":4.7,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10981997/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140331520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum.","authors":"Raja Amri, Ameni Chelly, Mariem Ayedi, Mohamed Ali Rebaii, Sami Aifa, Sabeur Masmoudi, Hassib Keskes","doi":"10.1302/2046-3758.134.BJR-2024-00002","DOIUrl":"10.1302/2046-3758.134.BJR-2024-00002","url":null,"abstract":"","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"13 4","pages":"136"},"PeriodicalIF":4.7,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10981995/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140331487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}