Bone & Joint Research最新文献

{"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}

{"title":"Implant retention in a rabbit model of fracture-related infection.","authors":"Jan Puetzler, Alejandro Vallejo Diaz, Georg Gosheger, Martin Schulze, Daniel Arens, Stephan Zeiter, Claudia Siverino, Robert G Richards, Thomas F Moriarty","doi":"10.1302/2046-3758.133.BJR-2023-0077.R2","DOIUrl":"10.1302/2046-3758.133.BJR-2023-0077.R2","url":null,"abstract":"<p><strong>Aims: </strong>Fracture-related infection (FRI) is commonly classified based on the time of onset of symptoms. Early infections (< two weeks) are treated with debridement, antibiotics, and implant retention (DAIR). For late infections (> ten weeks), guidelines recommend implant removal due to tolerant biofilms. For delayed infections (two to ten weeks), recommendations are unclear. In this study we compared infection clearance and bone healing in early and delayed FRI treated with DAIR in a rabbit model.</p><p><strong>Methods: </strong><i>Staphylococcus aureus</i> was inoculated into a humeral osteotomy in 17 rabbits after plate osteosynthesis. Infection developed for one week (early group, n = 6) or four weeks (delayed group, n = 6) before DAIR (systemic antibiotics: two weeks, nafcillin + rifampin; four weeks, levofloxacin + rifampin). A control group (n = 5) received revision surgery after four weeks without antibiotics. Bacteriology of humerus, soft-tissue, and implants was performed seven weeks after revision surgery. Bone healing was assessed using a modified radiological union scale in tibial fractures (mRUST).</p><p><strong>Results: </strong>Greater bacterial burden in the early group compared to the delayed and control groups at revision surgery indicates a retraction of the infection from one to four weeks. Infection was cleared in all animals in the early and delayed groups at euthanasia, but not in the control group. Osteotomies healed in the early group, but bone healing was significantly compromised in the delayed and control groups.</p><p><strong>Conclusion: </strong>The duration of the infection from one to four weeks does not impact the success of infection clearance in this model. Bone healing, however, is impaired as the duration of the infection increases.</p>","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"13 3","pages":"127-135"},"PeriodicalIF":4.7,"publicationDate":"2024-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10958740/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140183723","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":"Infographic: Chongqing technique.","authors":"Jie Shen, Zhiyuan Wei, Dong Sun, Hongri Wu, Xiaohua Wang, Shulin Wang, Fei Luo, Zhao Xie","doi":"10.1302/2046-3758.133.BJR-2023-0358","DOIUrl":"10.1302/2046-3758.133.BJR-2023-0358","url":null,"abstract":"","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"13 3","pages":"124-126"},"PeriodicalIF":4.7,"publicationDate":"2024-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10924692/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140093463","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":"Inhibition of SAT1 alleviates chondrocyte inflammation and ferroptosis by repressing ALOX15 expression and activating the Nrf2 pathway.","authors":"Jingting Xu, Zhaoxuan Ruan, Zhou Guo, Liangcai Hou, Genchun Wang, Zehang Zheng, Xiong Zhang, Haigang Liu, Kai Sun, Fengjing Guo","doi":"10.1302/2046-3758.133.BJR-2023-0250.R1","DOIUrl":"10.1302/2046-3758.133.BJR-2023-0250.R1","url":null,"abstract":"<p><strong>Aims: </strong>Osteoarthritis (OA) is the most common chronic pathema of human joints. The pathogenesis is complex, involving physiological and mechanical factors. In previous studies, we found that ferroptosis is intimately related to OA, while the role of Sat1 in chondrocyte ferroptosis and OA, as well as the underlying mechanism, remains unclear.</p><p><strong>Methods: </strong>In this study, interleukin-1β (IL-1β) was used to simulate inflammation and Erastin was used to simulate ferroptosis in vitro. We used small interfering RNA (siRNA) to knock down the spermidine/spermine N1-acetyltransferase 1 (Sat1) and arachidonate 15-lipoxygenase (Alox15), and examined damage-associated events including inflammation, ferroptosis, and oxidative stress of chondrocytes. In addition, a destabilization of the medial meniscus (DMM) mouse model of OA induced by surgery was established to investigate the role of Sat1 inhibition in OA progression.</p><p><strong>Results: </strong>The results showed that inhibition of Sat1 expression can reduce inflammation, ferroptosis changes, reactive oxygen species (ROS) level, and lipid-ROS accumulation induced by IL-1β and Erastin. Knockdown of Sat1 promotes nuclear factor-E2-related factor 2 (Nrf2) signalling. Additionally, knockdown Alox15 can alleviate the inflammation-related protein expression induced by IL-1β and ferroptosis-related protein expression induced by Erastin. Furthermore, knockdown Nrf2 can reverse these protein expression alterations. Finally, intra-articular injection of diminazene aceturate (DA), an inhibitor of Sat1, enhanced type II collagen (collagen II) and increased Sat1 and Alox15 expression.</p><p><strong>Conclusion: </strong>Our results demonstrate that inhibition of Sat1 could alleviate chondrocyte ferroptosis and inflammation by downregulating Alox15 activating the Nrf2 system, and delaying the progression of OA. These findings suggest that Sat1 provides a new approach for studying and treating OA.</p>","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"13 3","pages":"110-123"},"PeriodicalIF":4.7,"publicationDate":"2024-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10917474/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140048772","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":"Halicin remains active against Staphylococcus aureus in biofilms grown on orthopaedically relevant substrates.","authors":"Shota Higashihira, Stefanie J Simpson, Akira Morita, Joash R Suryavanshi, Christopher J Arnold, Roman M Natoli, Edward M Greenfield","doi":"10.1302/2046-3758.133.BJR-2023-0038.R2","DOIUrl":"10.1302/2046-3758.133.BJR-2023-0038.R2","url":null,"abstract":"<p><strong>Aims: </strong>Biofilm infections are among the most challenging complications in orthopaedics, as bacteria within the biofilms are protected from the host immune system and many antibiotics. Halicin exhibits broad-spectrum activity against many planktonic bacteria, and previous studies have demonstrated that halicin is also effective against <i>Staphylococcus aureus</i> biofilms grown on polystyrene or polypropylene substrates. However, the effectiveness of many antibiotics can be substantially altered depending on which orthopaedically relevant substrates the biofilms grow. This study, therefore, evaluated the activity of halicin against less mature and more mature <i>S. aureus</i> biofilms grown on titanium alloy, cobalt-chrome, ultra-high molecular weight polyethylene (UHMWPE), devitalized muscle, or devitalized bone.</p><p><strong>Methods: </strong><i>S. aureus</i>-Xen36 biofilms were grown on the various substrates for 24 hours or seven days. Biofilms were incubated with various concentrations of halicin or vancomycin and then allowed to recover without antibiotics. Minimal biofilm eradication concentrations (MBECs) were defined by CFU counting and resazurin reduction assays, and were compared with the planktonic minimal inhibitory concentrations (MICs).</p><p><strong>Results: </strong>Halicin continued to exert significantly (p < 0.01) more antibacterial activity against biofilms grown on all tested orthopaedically relevant substrates than vancomycin, an antibiotic known to be affected by biofilm maturity. For example, halicin MBECs against both less mature and more mature biofilms were ten-fold to 40-fold higher than its MIC. In contrast, vancomycin MBECs against the less mature biofilms were 50-fold to 200-fold higher than its MIC, and 100-fold to 400-fold higher against the more mature biofilms.</p><p><strong>Conclusion: </strong>Halicin is a promising antibiotic that should be tested in animal models of orthopaedic infection.</p>","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"13 3","pages":"101-109"},"PeriodicalIF":4.7,"publicationDate":"2024-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10909403/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140020924","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 high antibiotic concentrations applied to continuous local antibiotic perfusion on human bone tissue-derived cells.","authors":"Yuya Yamamoto, Tomoaki Fukui, Kenichi Sawauchi, Ryo Yoshikawa, Kyohei Takase, Yohei Kumabe, Akihiro Maruo, Takahiro Niikura, Ryosuke Kuroda, Keisuke Oe","doi":"10.1302/2046-3758.133.BJR-2023-0198.R1","DOIUrl":"10.1302/2046-3758.133.BJR-2023-0198.R1","url":null,"abstract":"<p><strong>Aims: </strong>Continuous local antibiotic perfusion (CLAP) has recently attracted attention as a new drug delivery system for orthopaedic infections. CLAP is a direct continuous infusion of high-concentration gentamicin (1,200 μg/ml) into the bone marrow. As it is a new system, its influence on the bone marrow is unknown. This study aimed to examine the effects of high-concentration antibiotics on human bone tissue-derived cells.</p><p><strong>Methods: </strong>Cells were isolated from the bone tissue grafts collected from six patients using the Reamer-Irrigator-Aspirator system, and exposed to different gentamicin concentrations. Live cells rate, apoptosis rate, alkaline phosphatase (ALP) activity, expression of osteoblast-related genes, mineralization potential, and restoration of cell viability and ALP activity were examined by in vitro studies.</p><p><strong>Results: </strong>The live cells rate (the ratio of total number of cells in the well plate to the absorbance-measured number of live cells) was significantly decreased at ≥ 500 μg/ml of gentamicin on day 14; apoptosis rate was significantly increased at ≥ 750 μg/ml, and ALP activity was significantly decreased at ≥ 750 μg/ml. Real-time reverse transcription-polymerase chain reaction results showed no significant decrease in the ALP and activating transcription factor 4 transcript levels at ≥ 1,000 μg/ml on day 7. Mineralization potential was significantly decreased at all concentrations. Restoration of cell viability was significantly decreased at 750 and 1,000 μg/ml on day 21 and at 500 μg/ml on day 28, and ALP activity was significantly decreased at 500 μg/ml on day 28.</p><p><strong>Conclusion: </strong>Our findings suggest that the exposure concentration and duration of antibiotic administration during CLAP could affect cell functions. However, further in vivo studies are needed to determine the optimal dose in a clinical setting.</p>","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"13 3","pages":"91-100"},"PeriodicalIF":4.7,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10904204/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139995555","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":"RANKL, OPG, and RUNX2 expression and epigenetic modifications in giant cell tumour of bone in 32 patients.","authors":"Raja Amri, Ameni Chelly, Mariem Ayedi, Mohamed Ali Rebaii, Sami Aifa, Sabeur Masmoudi, Hassib Keskes","doi":"10.1302/2046-3758.132.BJR-2023-0023.R2","DOIUrl":"10.1302/2046-3758.132.BJR-2023-0023.R2","url":null,"abstract":"<p><strong>Aims: </strong>The present study investigated receptor activator of nuclear factor kappa-Β ligand (RANKL), osteoprotegerin (OPG), and Runt-related transcription factor 2 (RUNX2) gene expressions in giant cell tumour of bone (GCTB) patients in relationship with tumour recurrence. We also aimed to investigate the influence of CpG methylation on the transcriptional levels of RANKL and OPG.</p><p><strong>Methods: </strong>A total of 32 GCTB tissue samples were analyzed, and the expression of RANKL, OPG, and RUNX2 was evaluated by quantitative polymerase chain reaction (qPCR). The methylation status of RANKL and OPG was also evaluated by quantitative methylation-specific polymerase chain reaction (qMSP).</p><p><strong>Results: </strong>We found that RANKL and RUNX2 gene expression was upregulated more in recurrent than in non-recurrent GCTB tissues, while OPG gene expression was downregulated more in recurrent than in non-recurrent GCTB tissues. Additionally, we proved that changes in DNA methylation contribute to upregulating the expression of RANKL and downregulating the expression of OPG, which are critical for bone homeostasis and GCTB development.</p><p><strong>Conclusion: </strong>Our results suggest that the overexpression of RANKL/RUNX2 and the lower expression of OPG are associated with recurrence in GCTB patients.</p>","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"13 2","pages":"83-90"},"PeriodicalIF":4.7,"publicationDate":"2024-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10875390/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139899318","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}