Hui Zang, Liuyan Wang, Yang Wu, Junfei Chang, Wanjun Liu
{"title":"Integrated bioinformatics and network pharmacology to identify and validate macrophage polarization related hub genes in the treatment of osteoarthritis with Astragalus membranaceus.","authors":"Hui Zang, Liuyan Wang, Yang Wu, Junfei Chang, Wanjun Liu","doi":"10.1186/s13018-025-05799-9","DOIUrl":"https://doi.org/10.1186/s13018-025-05799-9","url":null,"abstract":"<p><strong>Background: </strong>Macrophage polarization exacerbates the pathological processes of osteoarthritis (OA). Astragalus membranaceus (AM) can repair chondrocytes and serve as a protective agent for OA. Therefore, the study intended to identify macrophage polarization-related genes (MPRGs) in the treatment of OA with AM.</p><p><strong>Methods: </strong>We utilized data from GSE57218 as training set, while GSE117999 serves as a validation set, all obtained from Gene Expression Omnibus(GEO). The MPRGs were exported from the Molecular Signatures Database. Target genes of AM were obtained by network pharmacology. Differentially expressed genes (DEGs) were identified in OA vs. control groups. Then key module genes were acquired through weighted gene co-expression network analysis (WGCNA) and intersected with DEGs and target genes of AM to obtain candidate genes. Subsequently, the candidate genes were further screened for hub genes by machine learning, receiver operating characteristic (ROC) curve analysis, and expression validation. Further, reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) was applied to verify the mRNA expression levels of hub genes. In addition, the mechanism of these hub genes was investigated through enrichment analysis, immune microenvironment analysis, regulatory network construction, and molecular docking.</p><p><strong>Results: </strong>Ultimately, 1,430 DEGs, 4,577 key module genes, and 486 target genes of AM were intersected to derive 28 candidate genes. After machine learning, ROC curve analysis and expression validation, CREBBP and PIM3 were identified. The mRNA expression of tissue CREBBP and PIM3 was significantly decreased in OA compared with the control group. Furthermore, the enrichment analysis indicated that eight pathways, including oxidative phosphorylation, were simultaneously enriched by two hub genes. Microenvironment analysis revealed negative correlations between both hub genes and 11 differential immune cells. We identified that CREBBP and PIM3 were regulated by 6 miRNAs (e.g., hsa-mir-942-5p) and 79 transcription factors (TFs) (e.g., IRF1). Molecular docking experiments indicated that isoflavone strongly bound to CREBBP, while (3R)-3-(2-hydroxy-3,4-dimethoxyphenyl) chroman-7-ol exhibited significant binding affinity for PIM3, suggesting that these two active ingredients were core components of AM in treating OA via hub genes.</p><p><strong>Conclusion: </strong>This study identified CREBBP and PIM3 as potential focal points for the treatment of OA with AM, providing valuable clues to help treat and predict OA.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":16629,"journal":{"name":"Journal of Orthopaedic Surgery and Research","volume":"20 1","pages":"543"},"PeriodicalIF":2.8,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144183578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yiming Fan, Han Yu, Yi Huang, Chao Xue, Guoquan Zheng, Yan Wang
{"title":"Assessing radiological factors: the role of pelvic tilt in surgery for geriatric patients with degenerative spinal disorders.","authors":"Yiming Fan, Han Yu, Yi Huang, Chao Xue, Guoquan Zheng, Yan Wang","doi":"10.1186/s13018-025-05939-1","DOIUrl":"https://doi.org/10.1186/s13018-025-05939-1","url":null,"abstract":"","PeriodicalId":16629,"journal":{"name":"Journal of Orthopaedic Surgery and Research","volume":"20 1","pages":"544"},"PeriodicalIF":2.8,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144181863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Manar Y Abd El-Aziz, Doaa H Elgohary, Y A Abo El Amaim, Elham A Hassan
{"title":"Ex vivo mechanical testing of double strand, braided and knitted polyethylene suture for acute transverse section of the Achilles tendon in a dog model.","authors":"Manar Y Abd El-Aziz, Doaa H Elgohary, Y A Abo El Amaim, Elham A Hassan","doi":"10.1186/s13018-025-05947-1","DOIUrl":"https://doi.org/10.1186/s13018-025-05947-1","url":null,"abstract":"<p><strong>Background: </strong>Acute tendon cut represents a great challenge both in human and veterinary medical practice. The current study aimed to compare the ultimate biomechanical properties (tensile strength, elongation, stress load, yield load and break load) of double strand, braided and knitted polyethylene suture in an ex vivo model of acute transverse section of the Achilles tendon in dog model using locking loop suture and three-loop pulley suture.</p><p><strong>Methods: </strong>A-thirty-six Achilles tendon was transected from 18 dog cadavers. Tendon samples were randomly allocated (6 tendons/group) to be sutured either by double strand, braided and novel knitted formation techniques from polyethylene suture using either three-loop pulley suture or locking loop suture patterns. Biomechanical testing of different yarn for tensile strength, elongation, stress, yield load, break load was performed.</p><p><strong>Results: </strong>Braided polyethylene sutures demonstrated superior biomechanical properties, showing the highest maximum tension, load, stress, and yield load, while knitted sutures exhibited the greatest strain and elongation due to their looped structure. Despite the knitted yarn's high elongation, its tensile strength and load-bearing capabilities were significantly lower. Overall, yarn formation had a greater influence on biomechanical performance in association with suturing technique. The three-loop pulley suturing demonstrated significantly improved suturing outcomes.</p><p><strong>Conclusion: </strong>Both novel knitted, and braided suture structure demonstrated improved biomechanical properties of tendon suturing by increasing the number of strands within the tendon, simplifying the suturing process, reducing the needle passes, and minimizing tendon punctures that may interfere with healing and the overall strength. Suturing technique had a major influence on the biomechanical properties where the three-loop pulley suture demonstrated superior biomechanical properties compared to locking loop suturing.</p>","PeriodicalId":16629,"journal":{"name":"Journal of Orthopaedic Surgery and Research","volume":"20 1","pages":"545"},"PeriodicalIF":2.8,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144182460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yuanzhen Zhang, Jiayun Liu, Jinhua Yang, Ye Yuan, Guoyong Yin, Yu Zhang, Chun Lu
{"title":"Age-related traumatic anatomy and personalized medial incision design for calcaneal fractures in older adults using three-dimensional mapping.","authors":"Yuanzhen Zhang, Jiayun Liu, Jinhua Yang, Ye Yuan, Guoyong Yin, Yu Zhang, Chun Lu","doi":"10.1186/s13018-025-05934-6","DOIUrl":"https://doi.org/10.1186/s13018-025-05934-6","url":null,"abstract":"<p><strong>Background: </strong>Calcaneal fractures usually arise from high-energy trauma and predominantly impact young individuals. In older adults (aged ≥ 50 years), declining bone density and muscle strength increase fracture risk from low-energy trauma, leading to a bimodal epidemiological distribution. The intricacies of calcaneal fractures in older adults, alongside osteoporosis and soft tissue fragility, complicate surgical intervention. This study aims to analyze age-related differences in calcaneal fracture characteristics using three-dimensional(3D) mapping and assess their impact on medial incision design.</p><p><strong>Method: </strong>A total of 95 patients with closed calcaneal fractures were categorized into two groups: Younger (< 50 years, n = 61) and Older (≥ 50 years, n = 34). The process of 3D fracture mapping was executed utilizing Mimics and 3-matic software, alongside the reconstruction of soft tissue, which encompassed the posterior tibial neurovascular bundle. Differences in fracture distribution and incision parameters (length, α angle, D1, and D2) were statistically analyzed, with p < 0.05 considered statistically significant.</p><p><strong>Results: </strong>Fracture lines in both groups were predominantly located around the lateral Gissane's angle and critical weight-bearing areas of the calcaneus. In the Younger Group, fracture lines were long, continuous, and involved fewer fragments, correlating with high-energy trauma. The Older Group showed more comminuted lines, characteristic of osteoporotic fractures. The α angle and D1 distance were significantly smaller in the Older Group (p < 0.05), indicating closer proximity to the medial malleolus. D2 values were also smaller (p < 0.05), with 48.65% intersecting the neurovascular bundle compared to 31.34% in the Younger Group.</p><p><strong>Conclusion: </strong>Age significantly influences medial wall fracture patterns and complexity in calcaneal injuries. A personalized medial incision based on fracture morphology provides better exposure and reduction compared to traditional methods. Although the incision is closer to the neurovascular bundle in older patients, meticulous surgical technique guarantees safety. The integration of a medial incision with sinus-tarsi (ST) approach minimizes the necessity for extensive lateral exposure, thereby diminishing soft tissue complications and improving surgical outcomes for the elderly population.</p><p><strong>Level of evidence: </strong>Level IV, retrospective case series.</p>","PeriodicalId":16629,"journal":{"name":"Journal of Orthopaedic Surgery and Research","volume":"20 1","pages":"546"},"PeriodicalIF":2.8,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144181862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Leilei Gao, Hui Xiao, Rui Ma, Jun Liu, Xiaoxia Huang, Luyao Li, Kai Ye, Tao Liu, Yong Teng
{"title":"Prognostic factors of selective nerve root block under fluoroscopic guidance for the treatment of young patients with lumbar disc herniation and its role in preventing surgery.","authors":"Leilei Gao, Hui Xiao, Rui Ma, Jun Liu, Xiaoxia Huang, Luyao Li, Kai Ye, Tao Liu, Yong Teng","doi":"10.1186/s13018-025-05852-7","DOIUrl":"https://doi.org/10.1186/s13018-025-05852-7","url":null,"abstract":"<p><strong>Background: </strong>As a transitional treatment between conservative treatment and surgical treatment for lumbar disc herniation (LDH), selec tive nerve root block (SNRB) has attracted increasing attention recently. The objective of this study was to evaluate the efficacy and prognostic factors of SNRB in young patients with LDH.</p><p><strong>Methods: </strong>A prospective observational cohort study was employed. A total of 134 patients with LDH who received SNRB treatment in our hospital from January 2023 to August 2023 were selected and divided into a recurrence group and a nonrecurrence group according to whether they experienced recurrence after SNRB. The demographic characteristics, clinical and imaging data and SNRB-related information were compared between the two groups. Multivariate logistic regression was used to analyze the factors influencing symptom recurrence after SNRB surgery.</p><p><strong>Results: </strong>Surgery was avoided in 95.522%, 86.567%, 78.358% and 64.925% of the patients at 2 weeks, 3 months, 6 months and 12 months after SNRB treatment, respectively. Multivariate logistic regression analysis revealed that a disease course of ≥ 3 months (OR = 6.031, 95% CI: 2.592-14.035, P = 0.001) was an independent risk factor for postoperative recurrence of SNRB, and extreme lateral protrusion (OR = 0.273, 95% CI: 0.078-0.956, P = 0.042) and the HIZ sign (OR = 0.200, 95% CI: 0.057-0.702, P = 0.012) were protective factors against postoperative recurrence of SNRB.</p><p><strong>Conclusions: </strong>The curative effect of SNRB in the treatment of young patients with LDH is significant. A disease course of ≤ 3 months, far-lateral protrusion and the HIZ sign are predictors of good outcomes. In addition, SNRB combined with medication and physical therapy is recommended as an alternative to surgery for patients who do not have acute surgical indications.</p>","PeriodicalId":16629,"journal":{"name":"Journal of Orthopaedic Surgery and Research","volume":"20 1","pages":"540"},"PeriodicalIF":2.8,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144180876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gonzalo Mariscal, Francisco José Tarazona-Santabalbina, Oliver Marin-Peña, Erika Rotavista, Sara Arroyo Martín, María Estrella Fernández de Sevilla, Jesús Gómez-Vallejo
{"title":"Efficacy and safety of fondaparinux in elective total hip arthroplasty and hip fracture surgery: a systematic review and meta-analysis.","authors":"Gonzalo Mariscal, Francisco José Tarazona-Santabalbina, Oliver Marin-Peña, Erika Rotavista, Sara Arroyo Martín, María Estrella Fernández de Sevilla, Jesús Gómez-Vallejo","doi":"10.1186/s13018-025-05950-6","DOIUrl":"https://doi.org/10.1186/s13018-025-05950-6","url":null,"abstract":"<p><strong>Background: </strong>As life expectancy increases, the incidence of hip fractures and the demand for total hip arthroplasties (THA) are expected to rise. This demographic shift poses significant challenges, particularly in managing post-operative complications such as venous thromboembolism (VTE), a major cause of mortality. Despite advancements, the effectiveness of various anticoagulants, in preventing VTE post-THA or hip fracture surgery remains unclear due to conflicting study results. This study aims to thoroughly evaluate the efficacy and safety of fondaparinux in patients undergoing elective THA or hip fracture surgery.</p><p><strong>Methods: </strong>This review adhered to PRISMA guidelines. Inclusion criteria targeted studies on hip surgery patients treated with fondaparinux versus placebo or other anticoagulants. Data was collected from three major databases in November 2024 using the PICOS framework, focusing on following outcomes: venous thromboembolism, mortality, and bleeding rates. Meta-analysis utilized Review Manager 5.4, and applying a fixed-effects model unless significant heterogeneity (I² ≥ 50%) was detected. Sensitivity and subgroup analyses further refined the results based on surgery type and control groups.</p><p><strong>Results: </strong>Nineteen studies (n = 32534) were included in the meta-analysis. Fondaparinux significantly reduced the incidence of VTE compared to controls (OR 0.43, 95% CI 0.31 to 0.61) and low molecular weight heparins (LMWHs) (OR 0.55, 95% CI 0.41 to 0.74). The incidence of distal deep vein thrombosis (DVT) was also lower in fondaparinux group compared to LMWHs (OR 0.43, 95% CI 0.31 to 0.62). Proximal DVT showed a significant reduction overall (OR 0.33, 95% CI 0.15 to 0.75) in fondaparinux group, with no significant difference compared to enoxaparin specifically (OR 0.48, 95% CI 0.20 to 1.17). Additionally, there were no substantial differences in clinically significant bleeding. The average costs (euros, pounds and/or dollars) per patient per thromboembolic event at 90 days were lower in the fondaparinux group compared to enoxaparin, both in patients undergoing elective THA (132 vs. 216) and hip fracture surgery (339 vs. 518).</p><p><strong>Conclusion: </strong>Based on the results of this meta-analysis, fondaparinux significantly reduced VTE and DVT incidence compared to LMWHs in patients undergoing elective THA and hip fracture surgery, with a similar incidence of clinically significant bleeding. Additionally, it demonstrated lower costs per thrombsoembolic event per patient than enoxaparin.</p>","PeriodicalId":16629,"journal":{"name":"Journal of Orthopaedic Surgery and Research","volume":"20 1","pages":"538"},"PeriodicalIF":2.8,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144181887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A-485 alleviates postmenopausal osteoporosis by activating GLUD1 deacetylation through the SENP1-Sirt3 signal pathway.","authors":"Yinghong Ma, Xiaohua Zou, Qianhong Jian, Jiaxin Dong, Xianbing Huang, Yue Zhai, Li Qian","doi":"10.1186/s13018-025-05839-4","DOIUrl":"https://doi.org/10.1186/s13018-025-05839-4","url":null,"abstract":"<p><strong>Objective: </strong>Postmenopausal osteoporosis (OP) is a bone disease caused by estrogen deficiency. A-485 is a selective inhibitor of p300/CBP histone acetyltransferase (HAT) with potential regulatory effects on bone remodeling. This study aims to investigate the effects of A-485 on postmenopausal OP and its underlying mechanisms.</p><p><strong>Methods: </strong>For animal experiments, 61 female Wistar rats were used to establish an OP model through ovariectomy (OVX). The rats were administered with A-485 (100 mg/kg/day) via intraperitoneal injection for six weeks. Bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry (DXA). Histopathological changes were observed using HE and Masson's trichrome staining. ELISA was used to measure bone resorption markers (CTX-1, DPD) and the bone formation marker (P1NP) in rats. Osteoblast differentiation markers (Runx2, OCN), SENP1, Sirt3 expression levels, and GLUD1 acetylation were assessed via Western blot (WB) and RT-qPCR. In vitro, MC3T3-E1 osteogenic progenitor cells were cultured in osteogenic differentiation medium supplemented with ascorbic acid, β-glycerophosphate, dexamethasone, and fulvestrant. CCK-8 was performed to evaluate cell proliferation. Flow cytometry was selected to measure apoptosis and mitochondrial membrane potential. WB and RT-qPCR were employed to analyze ERα, ERβ, Runx2, Sirt3, and GLUD1 acetylation. Additionally, Alizarin red staining was applied to monitor osteoblast mineralization. ATP levels were detected using a commercial kit, and ROS levels were measured by MitoSOX Red.</p><p><strong>Results: </strong>In vivo, ovariectomized rats exhibited lower BMD, impaired bone trabeculae, increased CTX-1 and DPD, and altered expression of Runx2 and OCN, all of which were reversed by A-485 treatment. In vitro, A-485 activated GLUD1 deacetylation, enhanced osteogenic differentiation, and improved mitochondrial function. Regarding the mechanism, A-485 activated the SENP1-Sirt3 signal pathway, with SENP1 knockdown negating the effects of A-485. In vivo, A-485 reduced GLUD1 acetylation and promoted improvement of OP, which were reversed by SENP1 knockdown.</p><p><strong>Conclusion: </strong>A-485 ameliorates postmenopausal OP by activating GLUD1 deacetylation via the SENP1-Sirt3 signal pathway, thus improving mitochondrial function, and promoting osteogenic differentiation and mineralization.</p>","PeriodicalId":16629,"journal":{"name":"Journal of Orthopaedic Surgery and Research","volume":"20 1","pages":"542"},"PeriodicalIF":2.8,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144180026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xinrui Yin, Xue Tian, Bingyi Wang, Yi Yang, Xiaodong Tang, Yi Feng, Luyang Jiang
{"title":"The efficacy of combined lateral and anterior quadratus lumborum blocks in postoperative pain management following pelvic tumor resection: a randomized controlled trial.","authors":"Xinrui Yin, Xue Tian, Bingyi Wang, Yi Yang, Xiaodong Tang, Yi Feng, Luyang Jiang","doi":"10.1186/s13018-025-05968-w","DOIUrl":"https://doi.org/10.1186/s13018-025-05968-w","url":null,"abstract":"<p><strong>Background: </strong>A wide range of pain management techniques have been investigated following pelvic tumor resection and reconstruction surgery; however, the optimal components remain a subject of debate. In this prospective randomized controlled trial, we assessed the postoperative analgesic efficacy of integrating lateral quadratus lumborum block (Lateral-QLB) and anterior quadratus lumborum block (Anterior-QLB) with multimodal analgesia (MMA) regimen, compared to MMA regimen alone, in patients undergoing pelvic tumor resection and reconstruction.</p><p><strong>Methods: </strong>A total of 56 patients were randomly allocated to either the QLB group (n = 28) or the No Block group (n = 28). The QLB group received an ultrasound-guided Combined quadratus lumborum block (a combination of Lateral-QLB and Anterior-QLB), with 20 mL of 0.375% ropivacaine administered on each approach. The No Block group received standardized multimodal analgesia. Both groups followed an identical postoperative patient-controlled intravenous analgesia protocol. Outcomes included opioid consumption (intravenous morphine milligram equivalents, IV MME) at multiple time points within 48 h postoperatively, time to first opioid request, resting/activity-related pain scores, postoperative neurological assessments (lower extremity motor and sensory function), recovery quality quantified using QoR-15 (Quality of Recovery-15) scores on postoperative days (POD) 1, 2, and 7, and chronic pain prevalence during a 3-month follow-up.</p><p><strong>Results: </strong>The QLB group exhibited significant reductions in cumulative IV MME at 24 h (18.56 ± 6.63 vs. 24.29 ± 5.69 mg, p = 0.001) and 48 h (27.87 ± 9.95 vs. 41.29 ± 9.67 mg, p < 0.001), along with an extended time to the first opioid request (median 5.0 vs. 4.0 h, p = 0.005). Resting/activity pain scores were consistently lower (p = 0.008/p = 0.003), accompanied by transient sensory changes in the abdomen/thigh without motor impairment. QoR-15 scores significantly favored the QLB group (p < 0.05), with lower chronic pain rates at 3 months post-surgery compared to the No Block group (7.1% vs. 32.1%, p = 0.021).</p><p><strong>Conclusion: </strong>The ultrasound-guided QLB demonstrated superior analgesic efficacy and reduced morphine consumption compared to patients without the block. Our findings provide evidence supporting the hypothesis that QLB is an effective component of multimodal analgesia for individuals undergoing pelvic tumor resection and reconstructive surgery.</p>","PeriodicalId":16629,"journal":{"name":"Journal of Orthopaedic Surgery and Research","volume":"20 1","pages":"541"},"PeriodicalIF":2.8,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144182210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jun Yu, Ming Yang, Yun Jin, Kaijie Yang, Haibo Yang
{"title":"Insights into the potential role of BMSCs-exo delivered USP14 on SIRT1 deubiquitination in Staphylococcus aureus-induced model of osteomyelitis.","authors":"Jun Yu, Ming Yang, Yun Jin, Kaijie Yang, Haibo Yang","doi":"10.1186/s13018-025-05898-7","DOIUrl":"https://doi.org/10.1186/s13018-025-05898-7","url":null,"abstract":"<p><p>Osteomyelitis resulting from a traumatic fracture is a recurrent and difficult-to-treat bone infection. Ubiquitin-specific protease 14 (USP14), a deubiquitinating enzyme, and Sirtuin-1 (SIRT1), an NAD+-dependent deacetylase, both play critical roles in regulating cellular processes, including inflammation. It has been discovered that exosomes originated from bone marrow mesenchymal stem cells (BMSCs-exo) can promote the repair and regeneration of bone fractures. In this study, we aimed to investigate the role of BMSCs-exo in osteoblast differentiation in osteomyelitis and the related molecular mechanisms. MC3T3-E1 cells induced with S. aureus were used as an in vitro model of osteomyelitis. BMSCs-exo were isolated and characterized using ultracentrifugation, transmission electron microscopy (TEM), and Western blot. RT-qPCR, Western blot, CCK-8, ALP staining, ELISA, and CO-IP were utilized to evaluate USP14 and SIRT1 levels, the osteogenic differentiation ability of MC3T3-E1 cells, and the deubiquitination level of SIRT1. Low expression of USP14 and SIRT1 was observed in the bone tissue of osteomyelitis patients. BMSCs-exo could upregulate the expression of USP14 and promote the expression of SIRT1 protein in the cell model of osteomyelitis. In addition, BMSCs-exo reduced the levels of inflammatory factors TNFα and IL-6, enhanced cell viability, promoted the expression of osteogenic differentiation markers RUNX2 and OCN in MC3T3-E1 cells, and improved cell osteogenic capacity. However, these trends were significantly reversed in MC3T3-E1 cells following treatment with BMSCs-exo transfected with si-USP14. Furthermore, knockdown of USP14 promoted SIRT1 ubiquitination and degradation, the process that was reversed by the proteasome inhibitor MG132, whereas USP14 overexpression inhibited SIRT1 ubiquitination. In MC3T3-E1 cells infected with S. aureus, BMSCs-exo delivers USP14, which may enhance SIRT1 deubiquitination and increase SIRT1 protein activity. This process inhibits inflammation and promotes osteogenesis, warranting further investigation into its mechanisms and in vivo efficacy.</p>","PeriodicalId":16629,"journal":{"name":"Journal of Orthopaedic Surgery and Research","volume":"20 1","pages":"539"},"PeriodicalIF":2.8,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144180318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Targeting TYROBP to influence the immune microenvironment and osteogenic differentiation of mesenchymal stem cells.","authors":"Liangkun Huang, Zijie Pei, Tongyi Zhang, Ze Zhang, Fengpo Sun, Liangyuan Wen","doi":"10.1186/s13018-025-05925-7","DOIUrl":"https://doi.org/10.1186/s13018-025-05925-7","url":null,"abstract":"","PeriodicalId":16629,"journal":{"name":"Journal of Orthopaedic Surgery and Research","volume":"20 1","pages":"535"},"PeriodicalIF":2.8,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144174161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}