{"title":"Inhibition of PA28γ expression can alleviate osteoarthritis by inhibiting endoplasmic reticulum stress and promoting STAT3 phosphorylation.","authors":"Haokun Mo, Kai Sun, Yanjun Hou, Zhaoxuan Ruan, Zhiyi He, Haigang Liu, Liang Li, Zhenggang Wang, Fengjing Guo","doi":"10.1302/2046-3758.1311.BJR-2023-0361.R2","DOIUrl":"https://doi.org/10.1302/2046-3758.1311.BJR-2023-0361.R2","url":null,"abstract":"<p><strong>Aims: </strong>Osteoarthritis (OA) is a common degenerative disease. PA28γ is a member of the 11S proteasome activator and is involved in the regulation of several important cellular processes, including cell proliferation, apoptosis, and inflammation. This study aimed to explore the role of PA28γ in the occurrence and development of OA and its potential mechanism.</p><p><strong>Methods: </strong>A total of 120 newborn male mice were employed for the isolation and culture of primary chondrocytes. OA-related indicators such as anabolism, catabolism, inflammation, and apoptosis were detected. Effects and related mechanisms of PA28γ in chondrocyte endoplasmic reticulum (ER) stress were studied using western blotting, real-time polymerase chain reaction (PCR), and immunofluorescence. The OA mouse model was established by destabilized medial meniscus (DMM) surgery, and adenovirus was injected into the knee cavity of 15 12-week-old male mice to reduce the expression of PA28γ. The degree of cartilage destruction was evaluated by haematoxylin and eosin (HE) staining, safranin O/fast green staining, toluidine blue staining, and immunohistochemistry.</p><p><strong>Results: </strong>We found that PA28γ knockdown in chondrocytes can effectively improve anabolism and catabolism and inhibit inflammation, apoptosis, and ER stress. Moreover, PA28γ knockdown affected the phosphorylation of IRE1α and the expression of TRAF2, thereby affecting the mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) signalling pathways, and finally affecting the inflammatory response of chondrocytes. In addition, we found that PA28γ knockdown can promote the phosphorylation of signal transducer and activator of transcription 3 (STAT3), thereby inhibiting ER stress in chondrocytes. The use of Stattic (an inhibitor of STAT3 phosphorylation) enhanced ER stress. In vivo, we found that PA28γ knockdown effectively reduced cartilage destruction in a mouse model of OA induced by the DMM surgery.</p><p><strong>Conclusion: </strong>PA28γ knockdown in chondrocytes can inhibit anabolic and catabolic dysregulation, inflammatory response, and apoptosis in OA. Moreover, PA28γ knockdown in chondrocytes can inhibit ER stress by promoting STAT3 phosphorylation.</p>","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"13 11","pages":"659-672"},"PeriodicalIF":4.7,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675254","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}
Bone & Joint ResearchPub Date : 2024-11-12DOI: 10.1302/2046-3758.1311.BJR-2024-0247.R1
Kangpeng Li, Qiang Zhang
{"title":"Urgent focus on enhanced recovery after surgery of AIDS patients with limb fractures.","authors":"Kangpeng Li, Qiang Zhang","doi":"10.1302/2046-3758.1311.BJR-2024-0247.R1","DOIUrl":"10.1302/2046-3758.1311.BJR-2024-0247.R1","url":null,"abstract":"<p><strong>Aims: </strong>The incidence of limb fractures in patients living with HIV (PLWH) is increasing. However, due to their immunodeficiency status, the operation and rehabilitation of these patients present unique challenges. Currently, it is urgent to establish a standardized perioperative rehabilitation plan based on the concept of enhanced recovery after surgery (ERAS). This study aimed to validate the effectiveness of ERAS in the perioperative period of PLWH with limb fractures.</p><p><strong>Methods: </strong>A total of 120 PLWH with limb fractures, between January 2015 and December 2023, were included in this study. We established a multidisciplinary team to design and implement a standardized ERAS protocol. The demographic, surgical, clinical, and follow-up information of the patients were collected and analyzed retrospectively.</p><p><strong>Results: </strong>Compared with the control group, the ERAS group had a shorter operating time, hospital stay, preoperative waiting time, postoperative discharge time, less intraoperative blood loss, and higher albumin and haemoglobin on the first postoperative day. The time to removal of the urinary catheter/drainage tube was shortened, and the drainage volume was also significantly reduced in the ERAS group. There was no significant difference in the visual analogue scale (VAS) scores on postoperative return to the ward, but the ERAS group had lower scores on the first, second, and third postoperative days. There were no significant differences in the incidence of complications, other than 10% more nausea and vomiting in the control group. The limb function scores at one-year follow-up were similar between the two groups, but time to radiological fracture union and time to return to physical work and sports were significantly reduced in the ERAS group.</p><p><strong>Conclusion: </strong>The implementation of a series of perioperative nursing measures based on the concept of ERAS in PLWH with limb fracture can significantly reduce the operating time and intraoperative blood loss, reduce the occurrence of postoperative pain and complications, and accelerate the improvement of the functional status of the affected limb in the early stage, which is worthy of applying in more medical institutions.</p>","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"13 11","pages":"647-658"},"PeriodicalIF":4.7,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11555538/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142614493","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}
Bone & Joint ResearchPub Date : 2024-11-07DOI: 10.1302/2046-3758.1311.BJR-2024-0148.R1
Fernando Diaz Dilernia, David Watson, David Heinrichs, Edward Vasarhelyi
{"title":"The antimicrobial properties of exogenous copper in human synovial fluid against Staphylococcus aureus.","authors":"Fernando Diaz Dilernia, David Watson, David Heinrichs, Edward Vasarhelyi","doi":"10.1302/2046-3758.1311.BJR-2024-0148.R1","DOIUrl":"10.1302/2046-3758.1311.BJR-2024-0148.R1","url":null,"abstract":"<p><strong>Aims: </strong>The mechanism by which synovial fluid (SF) kills bacteria has not yet been elucidated, and a better understanding is needed. We sought to analyze the antimicrobial properties of exogenous copper in human SF against <i>Staphylococcus aureus</i>.</p><p><strong>Methods: </strong>We performed in vitro growth and viability assays to determine the capability of <i>S. aureus</i> to survive in SF with the addition of 10 µM of copper. We determined the minimum bactericidal concentration of copper (MBC-Cu) and evaluated its sensitivity to killing, comparing wild type (WT) and CopAZB-deficient USA300 strains.</p><p><strong>Results: </strong>UAMS-1 demonstrated a greater sensitivity to SF compared to USA300 WT at 12 hours (p = 0.001) and 24 hours (p = 0.027). UAMS-1 died in statistically significant quantities at 24 hours (p = 0.017), and USA300 WT survived at 24 hours. UAMS-1 was more susceptible to the addition of copper at four (p = 0.001), 12 (p = 0.005), and 24 hours (p = 0.006). We confirmed a high sensitivity to killing with the addition of exogenous copper on both strains at four (p = 0.011), 12 (p = 0.011), and 24 hours (p = 0.011). WT and CopAZB-deficient USA300 strains significantly died in SF, demonstrating a MBC-Cu of 50 µM against USA300 WT (p = 0.011).</p><p><strong>Conclusion: </strong>SF has antimicrobial properties against <i>S. aureus</i>, and UAMS-1 was more sensitive than USA300 WT. Adding 10 µM of copper was highly toxic, confirming its bactericidal effect. We found CopAZB proteins to be involved in copper effluxion by demonstrating the high sensitivity of mutant strains to lower copper concentrations. Thus, we propose CopAZB proteins as potential targets and use exogenous copper as a treatment alternative against <i>S. aureus</i>.</p>","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"13 11","pages":"632-646"},"PeriodicalIF":4.7,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11540464/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590074","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}
Bone & Joint ResearchPub Date : 2024-11-01DOI: 10.1302/2046-3758.1311.BJR-2023-0334.R2
David C Markel, Therese Bou-Akl, Bin Wu, Paula Pawlitz, Weiping Ren
{"title":"Efficacy of a saline wash plus vancomycin/tobramycin-doped PVA composite (PVA-VAN/TOB-P) in a mouse pouch infection model implanted with 3D-printed porous titanium cylinders.","authors":"David C Markel, Therese Bou-Akl, Bin Wu, Paula Pawlitz, Weiping Ren","doi":"10.1302/2046-3758.1311.BJR-2023-0334.R2","DOIUrl":"10.1302/2046-3758.1311.BJR-2023-0334.R2","url":null,"abstract":"<p><strong>Aims: </strong>The efficacy of saline irrigation for treatment of implant-associated infections is limited in the presence of porous metallic implants. This study evaluated the therapeutic efficacy of antibiotic doped bioceramic (vancomycin/tobramycin-doped polyvinyl alcohol composite (PVA-VAN/TOB-P)) after saline wash in a mouse infection model implanted with titanium cylinders.</p><p><strong>Methods: </strong>Air pouches created in female BalBc mice by subcutaneous injection of air. In the first of two independent studies, pouches were implanted with titanium cylinders (400, 700, and 100 µm pore sizes) and inoculated with <i>Staphylococcus aureus</i> (1 × 10<sup>3</sup> or 1 × 10<sup>6</sup> colony-forming units (CFU)/pouch) to establish infection and biofilm formation. Mice were killed after one week for microbiological analysis. In the second study, pouches were implanted with 400 µm titanium cylinders and inoculated with <i>S. aureus</i> (1 × 10<sup>3</sup> or 1 × 10<sup>6</sup> CFU/pouch). Four groups were tested: 1) no bacteria; 2) bacteria without saline wash; 3) saline wash only; and 4) saline wash plus PVA-VAN/TOB-P. After seven days, the pouches were opened and washed with saline alone, or had an additional injection of PVA-VAN/TOB-P. Mice were killed 14 days after pouch wash.</p><p><strong>Results: </strong>The first part of the study showed that low-grade infection was more significant in 400 µm cylinders than cylinders with larger pore sizes (p < 0.05). The second part of the study showed that saline wash alone was ineffective in eradicating both low- and high-grade infections. Saline plus PVA-VAN/TOB-P eradicated the titanium cylinder-associated infections, as manifested by negative cultures of the washouts and supported by scanning electron microscopy and histology.</p><p><strong>Conclusion: </strong>Porous titanium cylinders were vulnerable to bacterial infection and biofilm formation that could not be treated by saline irrigation alone. Application of PVA-VAN/TOB-P directly into the surgical site alone or after saline wash represents a feasible approach for prevention and/or treatment of porous implant-related infections.</p>","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"13 11","pages":"622-631"},"PeriodicalIF":4.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11527520/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557091","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}
Bone & Joint ResearchPub Date : 2024-10-24DOI: 10.1302/2046-3758.1310.BJR-2023-0362.R2
Qian Wan, Qing Han, Yang Liu, Hao Chen, Aobo Zhang, Xue Zhao, Jincheng Wang
{"title":"Appropriate sagittal positioning of femoral components in total knee arthroplasty to prevent fracture and loosening.","authors":"Qian Wan, Qing Han, Yang Liu, Hao Chen, Aobo Zhang, Xue Zhao, Jincheng Wang","doi":"10.1302/2046-3758.1310.BJR-2023-0362.R2","DOIUrl":"https://doi.org/10.1302/2046-3758.1310.BJR-2023-0362.R2","url":null,"abstract":"<p><strong>Aims: </strong>This study aimed to investigate the optimal sagittal positioning of the uncemented femoral component in total knee arthroplasty to minimize the risk of aseptic loosening and periprosthetic fracture.</p><p><strong>Methods: </strong>Ten different sagittal placements of the femoral component, ranging from -5 mm (causing anterior notch) to +4 mm (causing anterior gap), were analyzed using finite element analysis. Both gait and squat loading conditions were simulated, and Von Mises stress and interface micromotion were evaluated to assess fracture and loosening risk.</p><p><strong>Results: </strong>During gait, varied sagittal positioning did not lead to excessive Von Mises stress or micromotion. However, under squat conditions, posterior positioning (-4 and -5 mm) resulted in stress exceeding 150 MPa at the femoral notch, indicating potential fracture risk. Conversely, +1 mm and 0 mm sagittal positions demonstrated minimal interface micromotion.</p><p><strong>Conclusion: </strong>Slightly anterior sagittal positioning (+1 mm) or neutral positioning (0 mm) effectively reduced stress concentration at the femoral notch and minimized interface micromotion. Thus, these positions are deemed suitable to decrease the risk of aseptic loosening and periprosthetic femoral fracture.</p>","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"13 10","pages":"611-621"},"PeriodicalIF":4.7,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11500212/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494909","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}
Bone & Joint ResearchPub Date : 2024-10-21DOI: 10.1302/2046-3758.1310.BJR-2024-0026.R1
Stefan Toegel, Luca Martelanz, Juergen Alphonsus, Lena Hirtler, Ruth Gruebl-Barabas, Melanie Cezanne, Mario Rothbauer, Philipp Heuberer, Reinhard Windhager, Leo Pauzenberger
{"title":"The degenerated glenohumeral joint.","authors":"Stefan Toegel, Luca Martelanz, Juergen Alphonsus, Lena Hirtler, Ruth Gruebl-Barabas, Melanie Cezanne, Mario Rothbauer, Philipp Heuberer, Reinhard Windhager, Leo Pauzenberger","doi":"10.1302/2046-3758.1310.BJR-2024-0026.R1","DOIUrl":"10.1302/2046-3758.1310.BJR-2024-0026.R1","url":null,"abstract":"<p><strong>Aims: </strong>This study aimed to define the histopathology of degenerated humeral head cartilage and synovial inflammation of the glenohumeral joint in patients with omarthrosis (OmA) and cuff tear arthropathy (CTA). Additionally, the potential of immunohistochemical tissue biomarkers in reflecting the degeneration status of humeral head cartilage was evaluated.</p><p><strong>Methods: </strong>Specimens of the humeral head and synovial tissue from 12 patients with OmA, seven patients with CTA, and four body donors were processed histologically for examination using different histopathological scores. Osteochondral sections were immunohistochemically stained for collagen type I, collagen type II, collagen neoepitope C1,2C, collagen type X, and osteocalcin, prior to semiquantitative analysis. Matrix metalloproteinase (MMP)-1, MMP-3, and MMP-13 levels were analyzed in synovial fluid using enzyme-linked immunosorbent assay (ELISA).</p><p><strong>Results: </strong>Cartilage degeneration of the humeral head was associated with the histological presentation of: 1) pannus overgrowing the cartilage surface; 2) pores in the subchondral bone plate; and 3) chondrocyte clusters in OmA patients. In contrast, hyperplasia of the synovial lining layer was revealed as a significant indicator of inflammatory processes predominantly in CTA. The abundancy of collagen I, collagen II, and the C1,2C neoepitope correlated significantly with the histopathological degeneration of humeral head cartilage. No evidence for differences in MMP levels between OmA and CTA patients was found.</p><p><strong>Conclusion: </strong>This study provides a comprehensive histological characterization of humeral cartilage and synovial tissue within the glenohumeral joint, both in normal and diseased states. It highlights synovitis and pannus formation as histopathological hallmarks of OmA and CTA, indicating their roles as drivers of joint inflammation and cartilage degradation, and as targets for therapeutic strategies such as rotator cuff reconstruction and synovectomy.</p>","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"13 10","pages":"596-610"},"PeriodicalIF":4.7,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11491170/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457763","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}
Bone & Joint ResearchPub Date : 2024-10-17DOI: 10.1302/2046-3758.1310.BJR-2023-0275.R3
Rosmarie Breu, Carolina Avelar, Zsolt Bertalan, Johannes Grillari, Heinz Redl, Richard Ljuhar, Stefan Quadlbauer, Thomas Hausner
{"title":"Artificial intelligence in traumatology.","authors":"Rosmarie Breu, Carolina Avelar, Zsolt Bertalan, Johannes Grillari, Heinz Redl, Richard Ljuhar, Stefan Quadlbauer, Thomas Hausner","doi":"10.1302/2046-3758.1310.BJR-2023-0275.R3","DOIUrl":"https://doi.org/10.1302/2046-3758.1310.BJR-2023-0275.R3","url":null,"abstract":"<p><strong>Aims: </strong>The aim of this study was to create artificial intelligence (AI) software with the purpose of providing a second opinion to physicians to support distal radius fracture (DRF) detection, and to compare the accuracy of fracture detection of physicians with and without software support.</p><p><strong>Methods: </strong>The dataset consisted of 26,121 anonymized anterior-posterior (AP) and lateral standard view radiographs of the wrist, with and without DRF. The convolutional neural network (CNN) model was trained to detect the presence of a DRF by comparing the radiographs containing a fracture to the inconspicuous ones. A total of 11 physicians (six surgeons in training and five hand surgeons) assessed 200 pairs of randomly selected digital radiographs of the wrist (AP and lateral) for the presence of a DRF. The same images were first evaluated without, and then with, the support of the CNN model, and the diagnostic accuracy of the two methods was compared.</p><p><strong>Results: </strong>At the time of the study, the CNN model showed an area under the receiver operating curve of 0.97. AI assistance improved the physician's sensitivity (correct fracture detection) from 80% to 87%, and the specificity (correct fracture exclusion) from 91% to 95%. The overall error rate (combined false positive and false negative) was reduced from 14% without AI to 9% with AI.</p><p><strong>Conclusion: </strong>The use of a CNN model as a second opinion can improve the diagnostic accuracy of DRF detection in the study setting.</p>","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"13 10","pages":"588-595"},"PeriodicalIF":4.7,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11484119/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457761","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":"Employing single-cell RNA sequencing coupled with an array of bioinformatics approaches to ascertain the shared genetic characteristics between osteoporosis and obesity.","authors":"Dingzhuo Liu, Fangming Cao, Dian Liu, Hao Li, Lin Tao, Yue Zhu","doi":"10.1302/2046-3758.1310.BJR-2023-0366.R1","DOIUrl":"https://doi.org/10.1302/2046-3758.1310.BJR-2023-0366.R1","url":null,"abstract":"<p><strong>Aims: </strong>This study examined the relationship between obesity (OB) and osteoporosis (OP), aiming to identify shared genetic markers and molecular mechanisms to facilitate the development of therapies that target both conditions simultaneously.</p><p><strong>Methods: </strong>Using weighted gene co-expression network analysis (WGCNA), we analyzed datasets from the Gene Expression Omnibus (GEO) database to identify co-expressed gene modules in OB and OP. These modules underwent Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and protein-protein interaction analysis to discover Hub genes. Machine learning refined the gene selection, with further validation using additional datasets. Single-cell analysis emphasized specific cell subpopulations, and enzyme-linked immunosorbent assay (ELISA), protein blotting, and cellular staining were used to investigate key genes.</p><p><strong>Results: </strong>WGCNA revealed critical gene modules for OB and OP, identifying the <i>Toll-like receptor</i> (<i>TLR</i>) signalling pathway as a common factor. <i>TLR2</i> was the most significant gene, with a pronounced expression in macrophages. Elevated TLR2 expression correlated with increased adipose accumulation, inflammation, and osteoclast differentiation, linking it to OP development.</p><p><strong>Conclusion: </strong>Our study underscores the pivotal role of <i>TLR2</i> in connecting OP and OB. It highlights the influence of <i>TLR2</i> in macrophages, driving both diseases through a pro-inflammatory mechanism. These insights propose <i>TLR2</i> as a potential dual therapeutic target for treating OP and OB.</p>","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"13 10","pages":"573-587"},"PeriodicalIF":4.7,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11482281/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457762","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":"Mechanism research of elastic fixation promoting fracture healing based on proteomics and fracture microenvironment.","authors":"Weiyong Wu, Zhihui Zhao, Yongqing Wang, Meiyue Liu, Genbao Zhu, Lili Li","doi":"10.1302/2046-3758.1310.BJR-2023-0257.R2","DOIUrl":"https://doi.org/10.1302/2046-3758.1310.BJR-2023-0257.R2","url":null,"abstract":"<p><strong>Aims: </strong>This study aimed to demonstrate the promoting effect of elastic fixation on fracture, and further explore its mechanism at the gene and protein expression levels.</p><p><strong>Methods: </strong>A closed tibial fracture model was established using 12 male Japanese white rabbits, and divided into elastic and stiff fixation groups based on different fixation methods. Two weeks after the operation, a radiograph and pathological examination of callus tissue were used to evaluate fracture healing. Then, the differentially expressed proteins (DEPs) were examined in the callus using proteomics. Finally, in vitro cell experiments were conducted to investigate hub proteins involved in this process.</p><p><strong>Results: </strong>Mean callus volume was larger in the elastic fixation group (1,755 mm<sup>3</sup> (standard error of the mean (SEM) 297)) than in the stiff fixation group (258 mm<sup>3</sup> (SEM 65)). Pathological observation found that the expression levels of osterix (OSX), collagen, type I, alpha 1 (COL1α1), and alkaline phosphatase (ALP) in the callus of the elastic fixation group were higher than those of the stiff fixation group. The protein sequence of the callus revealed 199 DEPs, 124 of which were highly expressed in the elastic fixation group. In the in vitro study, it was observed that a stress of 200 g led to upregulation of thrombospondin 1 (THBS1) and osteoglycin (OGN) expression in bone marrow mesenchymal stem cells (BMSCs). Additionally, these genes were found to be upregulated during the osteogenic differentiation process of the BMSCs.</p><p><strong>Conclusion: </strong>Elastic fixation can promote fracture healing and osteoblast differentiation in callus, and the ability of elastic fixation to promote osteogenic differentiation of BMSCs may be achieved by upregulating genes such as THBS1 and OGN.</p>","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"13 10","pages":"559-572"},"PeriodicalIF":4.7,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11460404/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142387870","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}
Bone & Joint ResearchPub Date : 2024-10-04DOI: 10.1302/2046-3758.1310.BJR-2024-0119.R1
Yicheng Li, Shalitanati Wuermanbieke, Fei Wang, Wenbo Mu, Baochao Ji, Xiaobin Guo, Chen Zou, Yanyang Chen, Xiaogang Zhang, Li Cao
{"title":"Efficacy and safety of intra-articular-only meropenem after one-stage revision for treating Escherichia coli-induced periprosthetic joint infection in a rat model.","authors":"Yicheng Li, Shalitanati Wuermanbieke, Fei Wang, Wenbo Mu, Baochao Ji, Xiaobin Guo, Chen Zou, Yanyang Chen, Xiaogang Zhang, Li Cao","doi":"10.1302/2046-3758.1310.BJR-2024-0119.R1","DOIUrl":"10.1302/2046-3758.1310.BJR-2024-0119.R1","url":null,"abstract":"<p><strong>Aims: </strong>The optimum type of antibiotics and their administration route for treating Gram-negative (GN) periprosthetic joint infection (PJI) remain controversial. This study aimed to determine the GN bacterial species and antibacterial resistance rates related to clinical GN-PJI, and to determine the efficacy and safety of intra-articular (IA) antibiotic injection after one-stage revision in a GN pathogen-induced PJI rat model of total knee arthroplasty.</p><p><strong>Methods: </strong>A total of 36 consecutive PJI patients who had been infected with GN bacteria between February 2015 and December 2021 were retrospectively recruited in order to analyze the GN bacterial species involvement and antibacterial resistance rates. Antibiotic susceptibility assays of the GN bacterial species were performed to screen for the most sensitive antibiotic, which was then used to treat the most common GN pathogen-induced PJI rat model. The rats were randomized either to a PJI control group or to three meropenem groups (intraperitoneal (IP), IA, and IP + IA groups). After two weeks of treatment, infection control level, the side effects, and the volume of antibiotic use were evaluated.</p><p><strong>Results: </strong><i>Escherichia coli</i> was the most common pathogen in GN-PJI, and meropenem was the most sensitive antibiotic. Serum inflammatory markers, weightbearing activity, and Rissing score were significantly improved by meropenem, especially in the IA and IP + IA groups ( p < 0.05). Meropenem in the IA group eradicated <i>E. coli</i> from soft-tissue, bone, and prosthetic surfaces, with the same effect as in the IP + IA group. Radiological results revealed that IA and IP + IA meropenem were effective at relieving bone damage. Haematoxylin and eosin staining also showed that IA and IP + IA meropenem improved synovial inflammation and bone destruction. No pathological changes in the main organs or abnormal serum markers were observed in any of the meropenem-treated rats. The IA group required the lowest amount of meropenem, followed by the IP and IP + IA groups.</p><p><strong>Conclusion: </strong>IA-only meropenem with a two-week treatment course was effective and safe for PJI control following one-stage revision in a rat model, with less meropenem use.</p>","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"13 10","pages":"546-558"},"PeriodicalIF":4.7,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11449542/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142370950","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}