Bone & Joint Research最新文献

{"title":"Enhanced antibiofilm potential of low-intensity pulsed ultrasound combined with 0.35% povidone-iodine in a rat model of periprosthetic joint infection.","authors":"Tianxing Wang, Chenchen Yang, Guoqing Li, Yang Wang, Baochao Ji, Yongjie Chen, Haikang Zhou, Li Cao","doi":"10.1302/2046-3758.137.BJR-2023-0339.R1","DOIUrl":"10.1302/2046-3758.137.BJR-2023-0339.R1","url":null,"abstract":"<p><strong>Aims: </strong>Although low-intensity pulsed ultrasound (LIPUS) combined with disinfectants has been shown to effectively eliminate portions of biofilm in vitro, its efficacy in vivo remains uncertain. Our objective was to assess the antibiofilm potential and safety of LIPUS combined with 0.35% povidone-iodine (PI) in a rat debridement, antibiotics, and implant retention (DAIR) model of periprosthetic joint infection (PJI).</p><p><strong>Methods: </strong>A total of 56 male Sprague-Dawley rats were established in acute PJI models by intra-articular injection of bacteria. The rats were divided into four groups: a Control group, a 0.35% PI group, a LIPUS and saline group, and a LIPUS and 0.35% PI group. All rats underwent DAIR, except for Control, which underwent a sham procedure. General status, serum biochemical markers, weightbearing analysis, radiographs, micro-CT analysis, scanning electron microscopy of the prostheses, microbiological analysis, macroscope, and histopathology evaluation were performed 14 days after DAIR.</p><p><strong>Results: </strong>The group with LIPUS and 0.35% PI exhibited decreased levels of serum biochemical markers, improved weightbearing scores, reduced reactive bone changes, absence of viable bacteria, and decreased inflammation compared to the Control group. Despite the greater antibiofilm activity observed in the PI group compared to the LIPUS and saline group, none of the monotherapies were successful in preventing reactive bone changes or eliminating the infection.</p><p><strong>Conclusion: </strong>In the rat model of PJI treated with DAIR, LIPUS combined with 0.35% PI demonstrated stronger antibiofilm potential than monotherapy, without impairing any local soft-tissue.</p>","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"13 7","pages":"332-341"},"PeriodicalIF":4.7,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11223899/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141533498","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":"Effects of metformin on knee joint capsule fibrosis in a diabetic mouse model.","authors":"Toichiro Naito, Yoshiaki Yamanaka, Kotaro Tokuda, Naohito Sato, Takafumi Tajima, Manabu Tsukamoto, Hitoshi Suzuki, Makoto Kawasaki, Eiichiro Nakamura, Akinori Sakai","doi":"10.1302/2046-3758.137.BJR-2023-0384.R1","DOIUrl":"10.1302/2046-3758.137.BJR-2023-0384.R1","url":null,"abstract":"<p><strong>Aims: </strong>The antidiabetic agent metformin inhibits fibrosis in various organs. This study aims to elucidate the effects of hyperglycaemia and metformin on knee joint capsule fibrosis in mice.</p><p><strong>Methods: </strong>Eight-week-old wild-type (WT) and type 2 diabetic (db/db) mice were divided into four groups without or with metformin treatment (WT met(-/+), Db met(-/+)). Mice received daily intraperitoneal administration of metformin and were killed at 12 and 14 weeks of age. Fibrosis morphology and its related genes and proteins were evaluated. Fibroblasts were extracted from the capsules of 14-week-old mice, and the expression of fibrosis-related genes in response to glucose and metformin was evaluated in vitro.</p><p><strong>Results: </strong>The expression of all fibrosis-related genes was higher in Db met(-) than in WT met(-) and was suppressed by metformin. Increased levels of fibrosis-related genes, posterior capsule thickness, and collagen density were observed in the capsules of db/db mice compared with those in WT mice; these effects were suppressed by metformin. Glucose addition increased fibrosis-related gene expression in both groups of mice in vitro. When glucose was added, metformin inhibited the expression of fibrosis-related genes other than cellular communication network factor 2 (<i>Ccn2</i>) in WT mouse cells.</p><p><strong>Conclusion: </strong>Hyperglycaemia promotes fibrosis in the mouse knee joint capsule, which is inhibited by metformin. These findings can help inform the development of novel strategies for treating knee joint capsule fibrosis.</p>","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"13 7","pages":"321-331"},"PeriodicalIF":4.7,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11219202/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141490817","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":"Factors associated with Achilles tendon re-rupture following operative fixation.","authors":"Yoon Hyo Choi, Tae Hoon Kwon, Ji Hyun Choi, Hee Seok Han, Kyoung Min Lee","doi":"10.1302/2046-3758.137.BJR-2023-0258.R1","DOIUrl":"10.1302/2046-3758.137.BJR-2023-0258.R1","url":null,"abstract":"<p><strong>Aims: </strong>Achilles tendon re-rupture (ATRR) poses a significant risk of postoperative complication, even after a successful initial surgical repair. This study aimed to identify risk factors associated with Achilles tendon re-rupture following operative fixation.</p><p><strong>Methods: </strong>This retrospective cohort study analyzed a total of 43,287 patients from national health claims data spanning 2008 to 2018, focusing on patients who underwent surgical treatment for primary Achilles tendon rupture. Short-term ATRR was defined as cases that required revision surgery occurring between six weeks and one year after the initial surgical repair, while omitting cases with simultaneous infection or skin necrosis. Variables such as age, sex, the presence of Achilles tendinopathy, and comorbidities were systematically collected for the analysis. We employed multivariate stepwise logistic regression to identify potential risk factors associated with short-term ATRR.</p><p><strong>Results: </strong>From 2009 to 2018, the short-term re-rupture rate for Achilles tendon surgeries was 2.14%. Risk factors included male sex, younger age, and the presence of Achilles tendinopathy.</p><p><strong>Conclusion: </strong>This large-scale, big-data study reaffirmed known risk factors for short-term Achilles tendon re-rupture, specifically identifying male sex and younger age. Moreover, this study discovered that a prior history of Achilles tendinopathy emerges as an independent risk factor for re-rupture, even following initial operative fixation.</p>","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"13 7","pages":"315-320"},"PeriodicalIF":4.7,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11214864/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141466034","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":"Prosthetic spacers in two-stage revision for knee periprosthetic joint infection achieve better function and similar infection control.","authors":"Baijian Wu, Jinhui Su, Zhishuo Zhang, Jinyuan Zeng, Xinyu Fang, Wenbo Li, Wenming Zhang, Zida Huang","doi":"10.1302/2046-3758.136.BJR-2023-0251.R1","DOIUrl":"10.1302/2046-3758.136.BJR-2023-0251.R1","url":null,"abstract":"<p><strong>Aims: </strong>To explore the clinical efficacy of using two different types of articulating spacers in two-stage revision for chronic knee periprosthetic joint infection (kPJI).</p><p><strong>Methods: </strong>A retrospective cohort study of 50 chronic kPJI patients treated with two types of articulating spacers between January 2014 and March 2022 was conducted. The clinical outcomes and functional status of the different articulating spacers were compared. Overall, 17 patients were treated with prosthetic spacers (prosthetic group (PG)), and 33 patients were treated with cement spacers (cement group (CG)). The CG had a longer mean follow-up period (46.67 months (SD 26.61)) than the PG (24.82 months (SD 16.46); p = 0.001).</p><p><strong>Results: </strong>Infection was eradicated in 45 patients overall (90%). The PG had a better knee range of motion (ROM) and Knee Society Score (KSS) after the first-stage revision (p = 0.004; p = 0.002), while both groups had similar ROMs and KSSs at the last follow-up (p = 0.136; p = 0.895). The KSS in the CG was significantly better at the last follow-up (p = 0.013), while a larger percentage (10 in 17, 58.82%) of patients in the PG chose to retain the spacer (p = 0.008).</p><p><strong>Conclusion: </strong>Prosthetic spacers and cement spacers are both effective at treating chronic kPJI because they encourage infection control, and the former improved knee function status between stages. For some patients, prosthetic spacers may not require reimplantation.</p>","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"13 6","pages":"306-314"},"PeriodicalIF":4.7,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11188966/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141417704","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":"Panoramic heat map for spatial distribution of necrotic lesions.","authors":"Peng Yang, Wei He, Weiming Yang, Luoyong Jiang, Tianye Lin, Weichao Sun, Qingwen Zhang, Xueling Bai, Da Guo, Wei Sun","doi":"10.1302/2046-3758.136.BJR-2023-0181.R2","DOIUrl":"10.1302/2046-3758.136.BJR-2023-0181.R2","url":null,"abstract":"<p><strong>Aims: </strong>In this study, we aimed to visualize the spatial distribution characteristics of femoral head necrosis using a novel measurement method.</p><p><strong>Methods: </strong>We retrospectively collected CT imaging data of 108 hips with non-traumatic osteonecrosis of the femoral head from 76 consecutive patients (mean age 34.3 years (SD 8.1), 56.58% male (n = 43)) in two clinical centres. The femoral head was divided into 288 standard units (based on the orientation of units within the femoral head, designated as N[Superior], S[Inferior], E[Anterior], and W[Posterior]) using a new measurement system called the longitude and latitude division system (LLDS). A computer-aided design (CAD) measurement tool was also developed to visualize the measurement of the spatial location of necrotic lesions in CT images. Two orthopaedic surgeons independently performed measurements, and the results were used to draw 2D and 3D heat maps of spatial distribution of necrotic lesions in the femoral head, and for statistical analysis.</p><p><strong>Results: </strong>The results showed that the LLDS has high inter-rater reliability. As illustrated by the heat map, the distribution of Japanese Investigation Committee (JIC) classification type C necrotic lesions exhibited clustering characteristics, with the lesions being concentrated in the northern and eastern regions, forming a hot zone (90% probability) centred on the N4-N6E2, N3-N6E units of outer ring blocks. Statistical results showed that the distribution difference between type C2 and type C1 was most significant in the E1 and E2 units and, combined with the heat map, indicated that the spatial distribution differences at N3-N6E1 and N1-N3E2 units are crucial in understanding type C1 and C2 necrotic lesions.</p><p><strong>Conclusion: </strong>The LLDS can be used to accurately measure the spatial location of necrotic lesions and display their distribution characteristics.</p>","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"13 6","pages":"294-305"},"PeriodicalIF":4.6,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11181948/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141330336","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":"Adenosine, lidocaine, and magnesium therapy augments joint tissue healing following experimental anterior cruciate ligament rupture and reconstruction.","authors":"Jodie L Morris, Hayley L Letson, Peter C McEwen, Geoffrey P Dobson","doi":"10.1302/2046-3758.136.BJR-2023-0360.R1","DOIUrl":"10.1302/2046-3758.136.BJR-2023-0360.R1","url":null,"abstract":"<p><strong>Aims: </strong>Adenosine, lidocaine, and Mg²⁺ (ALM) therapy exerts differential immuno-inflammatory responses in males and females early after anterior cruciate ligament (ACL) reconstruction (ACLR). Our aim was to investigate sex-specific effects of ALM therapy on joint tissue repair and recovery 28 days after surgery.</p><p><strong>Methods: </strong>Male (n = 21) and female (n = 21) adult Sprague-Dawley rats were randomly divided into ALM or Saline control treatment groups. Three days after ACL rupture, animals underwent ACLR. An ALM or saline intravenous infusion was commenced prior to skin incision, and continued for one hour. An intra-articular bolus of ALM or saline was also administered prior to skin closure. Animals were monitored to 28 days, and joint function, pain, inflammatory markers, histopathology, and tissue repair markers were assessed.</p><p><strong>Results: </strong>Despite comparable knee function, ALM-treated males had reduced systemic inflammation, synovial fluid angiogenic and pro-inflammatory mediators, synovitis, and fat pad fibrotic changes, compared to controls. Within the ACL graft, ALM-treated males had increased expression of tissue repair markers, decreased inflammation, increased collagen organization, and improved graft-bone healing. In contrast to males, females had no evidence of persistent systemic inflammation. Compared to controls, ALM-treated females had improved knee extension, gait biomechanics, and elevated synovial macrophage inflammatory protein-1 alpha (MIP-1α). Within the ACL graft, ALM-treated females had decreased inflammation, increased collagen organization, and improved graft-bone healing. In articular cartilage of ALM-treated animals, matrix metalloproteinase (MMP)-13 expression was blunted in males, while in females repair markers were increased.</p><p><strong>Conclusion: </strong>At 28 days, ALM therapy reduces inflammation, augments tissue repair patterns, and improves joint function in a sex-specific manner. The study supports transition to human safety trials.</p>","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"13 6","pages":"279-293"},"PeriodicalIF":4.6,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11156504/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141282905","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":"Vibratory insertion of press-fit acetabular components requires less force than a single blow technique.","authors":"Yasaman Niki, Gerd Huber, Kambiz Behzadi, Michael M Morlock","doi":"10.1302/2046-3758.136.BJR-2023-0263.R1","DOIUrl":"10.1302/2046-3758.136.BJR-2023-0263.R1","url":null,"abstract":"<p><strong>Aims: </strong>Periprosthetic fracture and implant loosening are two of the major reasons for revision surgery of cementless implants. Optimal implant fixation with minimal bone damage is challenging in this procedure. This pilot study investigates whether vibratory implant insertion is gentler compared to consecutive single blows for acetabular component implantation in a surrogate polyurethane (PU) model.</p><p><strong>Methods: </strong>Acetabular components (cups) were implanted into 1 mm nominal under-sized cavities in PU foams (15 and 30 per cubic foot (PCF)) using a vibratory implant insertion device and an automated impaction device for single blows. The impaction force, remaining polar gap, and lever-out moment were measured and compared between the impaction methods.</p><p><strong>Results: </strong>Impaction force was reduced by 89% and 53% for vibratory insertion in 15 and 30 PCF foams, respectively. Both methods positioned the component with polar gaps under 2 mm in 15 PCF foam. However, in 30 PCF foam, the vibratory insertion resulted in a clinically undesirable polar gap of over 2 mm. A higher lever-out moment was achieved with the consecutive single blow insertion by 42% in 15 PCF and 2.7 times higher in 30 PCF foam.</p><p><strong>Conclusion: </strong>Vibratory implant insertion may lower periprosthetic fracture risk by reducing impaction forces, particularly in low-quality bone. Achieving implant seating using vibratory insertion requires adjustment of the nominal press-fit, especially in denser bone. Further preclinical testing on real bone tissue is necessary to assess whether its viscoelasticity in combination with an adjusted press-fit can compensate for the reduced primary stability after vibratory insertion observed in this study.</p>","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"13 6","pages":"272-278"},"PeriodicalIF":4.6,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11150042/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141247066","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":"Cartilage oligomeric matrix protein as a potential biomarker for knee osteoarthritis.","authors":"Wanvisa Udomsinprasert, Natcha Mookkhan, Thanyalak Tabtimnark, Teerapong Aramruang, Tachatra Ungsudechachai, Wacharapol Saengsiwaritt, Jiraphun Jittikoon, Usa Chaikledkaew, Sittisak Honsawek","doi":"10.1302/2046-3758.136.BJR-2023-0180.R1","DOIUrl":"10.1302/2046-3758.136.BJR-2023-0180.R1","url":null,"abstract":"<p><strong>Aims: </strong>This study aimed to determine the expression and clinical significance of a cartilage protein, cartilage oligomeric matrix protein (COMP), in knee osteoarthritis (OA) patients.</p><p><strong>Methods: </strong>A total of 270 knee OA patients and 93 healthy controls were recruited. COMP messenger RNA (mRNA) and protein levels in serum, synovial fluid, synovial tissue, and fibroblast-like synoviocytes (FLSs) of knee OA patients were determined using enzyme-linked immunosorbent assay, real-time polymerase chain reaction, and immunohistochemistry.</p><p><strong>Results: </strong>COMP protein levels were significantly elevated in serum and synovial fluid of knee OA patients, especially those in the advanced stages of the disease. Serum COMP was significantly correlated with radiological severity as well as measures of body composition, physical performance, knee pain, and disability. Receiver operating characteristic curve analysis unveiled a diagnostic value of serum COMP as a biomarker of knee OA (41.64 ng/ml, area under the curve (AUC) = 1.00), with a sensitivity of 99.6% and a specificity of 100.0%. Further analysis uncovered that <i>COMP</i> mRNA expression was markedly upregulated in the inflamed synovium of knee OA, consistent with immunohistochemical staining revealing localization of COMP protein in the lining and sub-lining layers of knee OA inflamed synovium. Most notably, relative <i>COMP</i> mRNA expression in knee OA synovium was positively associated with its protein levels in serum and synovial fluid of knee OA patients. In human knee OA FLSs activated with tumour necrosis factor-alpha, <i>COMP</i> mRNA expression was considerably up-regulated in a time-dependent manner.</p><p><strong>Conclusion: </strong>All results indicate that COMP might serve as a supportive diagnostic marker for knee OA in conjunction with the standard diagnostic methods.</p>","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"13 6","pages":"261-271"},"PeriodicalIF":4.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11142849/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141199354","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":"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":4.6,"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":"https://doi.org/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":4.6,"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}