Journal of Orthopaedic Translation最新文献

{"title":"Augmentation of functional recovery via ROCK/PI3K/AKT pathway by Fasudil Hydrochloride in a rat sciatic nerve transection model","authors":"Hai Wang , Fang Fang , Xing jing , Dan Xu , Zhenyu Ren , Shuang Dou , Yun Xie , Yuehong Zhuang","doi":"10.1016/j.jot.2024.06.006","DOIUrl":"https://doi.org/10.1016/j.jot.2024.06.006","url":null,"abstract":"<div><h3>Backgrounds</h3><p>The functional recovery after peripheral nerve injury remains unsatisfactory. This study aims to perform a comprehensive evaluation of the efficacy of Fasudil Hydrochloride at treating the sciatic nerve transection injury in rats and the mechanism involved.</p></div><div><h3>Materials and methods</h3><p>In animal experiments, 75 Sprague Dawley rats that underwent transection and repair of the right sciatic nerve were divided into a control, Fasudil, and Fas + LY group, receiving daily intraperitoneal injection of saline, Fasudil Hydrochloride (10 mg/kg), and Fasudil Hydrochloride plus LY294002 (5 mg/kg), respectively. At day 3 after surgery, the expression of ROCK2, p-PI3K, and p-AKT in L<sub>4-5</sub> DRG and the lumbosacral enlargement was determined using Western blotting. At day 7 and 14, axon density in the distal stump was evaluated with immunostaining using the anti-Neurofilament-200 antibody. At day 30, retrograde tracing by injecting Fluoro-gold in the distal stump was performed. Three months after surgery, remyelination was analyzed with immostaining using the anti-MPZ antibody and the transmission electron microscope; Moreover, Motion-Evoked Potential, and recovery of sensorimotor functions was evaluated with a neuromonitor, Footprint, Hot Plate and Von Frey Filaments, respectively. Moveover, the Gastrocnemius muscles were weighed, and then underwent H＆E staining, and staining of the neuromuscular junction using α-Bungarotoxin to evaluate the extent of atrophy and degeneration of the endplates in the Gastrocnemius. In vitro, spinal motor neurons (SMNs) and dorsal root ganglia (DRG) were cultured to examine the impact of Fasudil Hydrochloride and LY294002 on the axon outgrowth.</p></div><div><h3>Results</h3><p>Three days after injury, the expression of ROCK2 increased significantly (P＜0.01), and Fasudil application significantly increased the expression of p-PI3K and p-AKT in L<sub>4-6</sub> DRG and the lumbosacral enlargement (P < 0.05). At day 7 and 14 after surgery, a higher axon density could be observed in the Fasudil group(P < 0.05). At day 30 after surgery, a larger number of motor and sensory neurons absorbing Fluoro-gold could be observed in the Fasudil group (P < 0.01) Three months after surgery, a greater thickness of myelin sheath could be observed in the Fasudil group (P < 0.05). The electrophysiological test showed that a larger amplitude of motion-evoked potential could be triggered in the Fasudil group (P < 0.01). Behavioral tests showed that a higher sciatic function index and a lower threshold for reacting to heat and mechanical stimuli could be measured in the Fasudil group. (P < 0.01). The wet weight ratio of the Gastrocnemius muscles and the area of the cross section of its myofibrils were greater in the Fasudil group (P < 0.01), which also demonstrated a higer ratio of axon-endplate connection and a larger size of endplates (P < 0.05). And there were no significan","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"47 ","pages":"Pages 74-86"},"PeriodicalIF":5.9,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214031X24000548/pdfft?md5=5457b8ff320753f3be4fc5f775415d4b&pid=1-s2.0-S2214031X24000548-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141435034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting the senescence-related genes MAPK12 and FOS to alleviate osteoarthritis","authors":"Nana Geng ,&nbsp;Menglin Xian ,&nbsp;Lin Deng ,&nbsp;Biao Kuang ,&nbsp;Yiming Pan ,&nbsp;Kaiwen Liu ,&nbsp;Yuanlan Ye ,&nbsp;Mengtian Fan ,&nbsp;Zhixun Bai ,&nbsp;Fengjin Guo","doi":"10.1016/j.jot.2024.06.008","DOIUrl":"https://doi.org/10.1016/j.jot.2024.06.008","url":null,"abstract":"<div><h3>Background</h3><p>The mechanism by which chondrocyte senescence aggravate OA progression has not yet been well elucidated. The aim of this study was to investigate the chondrocyte senescence related gene biosignatures in OA, and to analyze on the underlying mechanisms of senescence in OA.</p></div><div><h3>Materials and methods</h3><p>We intersected osteoarthritis dataset GSE82107 from GEO database and senescence dataset from CellAge database of human senescence-associated genes based on genetic manipulations experiments plus gene expression profilin, and screened out 4 overlapping genes. The hub genes were verified <em>in vitro</em> and in human OA cartilage tissues by qRT-PCR. We further confirmed the function of mitogen-activated protein kinase 12 (MAPK12) and Fos proto-oncogene (FOS) in OA <em>in vitro</em> and <em>in vivo</em> by qRT-PCR, western blotting, Edu staining, immunofluorescence, SA-β-gal staining, HE, IHC, von frey test, and hot plate.</p></div><div><h3>Results</h3><p>1458 downregulated and 218 upregulated DEGs were determined from GSE82107, and 279 human senescence-associated genes were downloaded from CellAge database. After intersection assay, we screened out 4 overlapping genes, of which FOS, CYR61 and TNFSF15 were upregulated, MAPK12 was downregulated. The expression of MAPK12 was obviously downregulated, whereas the expression profiles of FOS, CYR61 and TNFSF15 were remarkedly upregulated in H₂O₂- or IL-1β-stimulated C28/I2 cells, human OA cartilage tissues, and knee cartilage of aging mice. Furthermore, both MAPK12 over-expression and FOS knock-down can promote cell proliferation and cartilage anabolism, inhibit cell senescence and cartilage catabolism, relieve joint pain in H₂O₂- or IL-1β-stimulated C28/I2 cells and mouse primary chondrocytes, destabilization of the medial meniscus (DMM) mice.</p></div><div><h3>Conclusion</h3><p>This study explored that MAPK12 and FOS are involved in the occurrence and development of OA through modulating chondrocyte senescence. They might be biomarkers of OA chondrocyte senescence, and provides some evidence as subsequent possible therapeutic targets for OA.</p></div><div><h3>The translational potential of this article</h3><p>The translation potential of this article is that we revealed MAPK12 and FOS can effectively alleviate OA by regulating chondrocyte senescence, and thus provided potential therapeutic targets for prevention or treatment of OA in the future.</p></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"47 ","pages":"Pages 50-62"},"PeriodicalIF":5.9,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214031X24000615/pdfft?md5=a8c50c0a6e9695d30505cdf1f9b17a6c&pid=1-s2.0-S2214031X24000615-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141435062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative effect of skeletal stem cells versus bone marrow mesenchymal stem cells on rotator cuff tendon-bone healing","authors":"Linfeng Wang ,&nbsp;Changbiao Guan ,&nbsp;Tao Zhang ,&nbsp;Yongchun Zhou ,&nbsp;Yuqian Liu ,&nbsp;Jianzhong Hu ,&nbsp;Daqi Xu ,&nbsp;Hongbin Lu","doi":"10.1016/j.jot.2024.05.005","DOIUrl":"https://doi.org/10.1016/j.jot.2024.05.005","url":null,"abstract":"<div><h3>Background</h3><p>Bone marrow mesenchymal stem cells (BMSCs) have immense potential in applications for the enhancement of tendon-bone (T-B) healing. Recently, it has been well-reported that skeletal stem cells (SSCs) could induce bone and cartilage regeneration. Therefore, SSCs represent a promising choice for cell-based therapies to improve T-B healing. In this study, we aimed to compare the therapeutic potential of SSCs and BMSCs for tendon-bone healing.</p></div><div><h3>Methods</h3><p>SSCs and BMSCs were isolated by flow cytometry, and their proliferation ability was measured by CCK-8 assay. The osteogenic, chondrogenic, and adipogenic gene expression in cells was detected by quantitative real-time polymerase chain reaction (qRT-PCR). C57BL/6 mice underwent unilateral supraspinatus tendon detachment and repair, and the mice were then randomly allocated to 4 groups: control group (tendon-bone interface without any treatment), hydrogel group (administration of blank hydrogel into the tendon-bone interface), hydrogel + BMSCs group (administration of hydrogel with BMSCs into the tendon-bone interface), and hydrogel + SSCs group (administration of hydrogel with SSCs into the tendon-bone interface). Histological staining, Micro-computed tomography (Micro-CT) scanning, biomechanical testing, and qRT-PCR were performed to assay T-B healing at 4 and 8 weeks after surgery.</p></div><div><h3>Results</h3><p>SSCs showed more cell proportion, exhibited stronger multiplication capacity, and expressed higher osteogenic and chondrogenic markers and lower adipogenic markers than BMSCs. In vivo assay, the SSCs group showed a better-maturated interface which was characterized by richer chondrocytes and more proteoglycan deposition, as well as more newly formed bone at the healing site and increased mechanical properties when compared to other there groups. qRT-PCR analysis revealed that the healing interface in the SSCs group expressed more transcription factors essential for osteogenesis and chondrogenesis than the interfaces in the other groups.</p></div><div><h3>Conclusions</h3><p>Overall, the results demonstrated the superior therapeutic potential of SSCs over BMSCs in tendon-bone healing.</p></div><div><h3>The translational potential of this article</h3><p>This current study provides valuable insights that SSCs may be a more effective cell therapy for enhancing T-B healing compared to BMSCs.</p></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"47 ","pages":"Pages 87-96"},"PeriodicalIF":5.9,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214031X24000470/pdfft?md5=4cdf608ebbe811e6e99cac3bb119dd42&pid=1-s2.0-S2214031X24000470-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141435063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Wnt/β-catenin signaling pathway as an important mediator in muscle and bone crosstalk: A systematic review","authors":"Wujian Lin ,&nbsp;Simon Kwoon Ho Chow ,&nbsp;Can Cui ,&nbsp;Chaoran Liu ,&nbsp;Qianjin Wang ,&nbsp;Senlin Chai ,&nbsp;Ronald Man Yeung Wong ,&nbsp;Ning Zhang ,&nbsp;Wing Hoi Cheung","doi":"10.1016/j.jot.2024.06.003","DOIUrl":"https://doi.org/10.1016/j.jot.2024.06.003","url":null,"abstract":"<div><h3>Background</h3><p>The interaction between muscle and bone is shown to be clinically important but the underlying mechanisms are largely unknown. The canonical Wnt/β-catenin signaling pathway is reported to be involved in muscle-bone crosstalk, but its detailed function remains unclear. This systematic review aims to investigate and elucidate the role of the Wnt/β-catenin signaling pathways in muscle-bone crosstalk.</p></div><div><h3>Methods</h3><p>We conducted a literature search on the Web of Science, PubMed, EBSCO and Embase with keywords “Wnt*”, “bone*” and “muscle*”. A systematic review was completed according to the guideline of preferred reporting items of systematic reviews and meta-analyses (PRISMA). Data synthesis included species (human, animal or cell type used), treatments involved, outcome measures and key findings with respect to Wnts.</p></div><div><h3>Results</h3><p>Seventeen papers were published from 2007 to 2021 and were extracted from a total of 1529 search results in the databases of Web of Science (468 papers), PubMed (457 papers), EBSCO (371) and Embase (233). 12 Wnt family members were investigated in the papers, including Wnt1, Wnt2, Wnt2b, Wnt3a, Wnt4, Wnt5a, Wnt8a, Wnt8b, Wnt9a, Wnt10a, Wnt10b and Wnt16. Many studies showed that muscles were able to increase or decrease osteogenesis of bone, while bone increased myogenesis of muscle through Wnt/β-catenin signaling pathways. Wnt3a, Wnt4 and Wnt10b were shown to play important roles in the crosstalk between muscle and bone.</p></div><div><h3>Conclusions</h3><p>Wnt3a, Wnt4 and Wnt10b are found to play important mediatory roles in muscle-bone crosstalk. The role of Wnt4 was mostly found to regulate muscle from the bone side. Whilst the role of Wnt10b during muscle ageing was proposed, current evidence is insufficient to clarify the specific role of Wnt/β-catenin signaling in the interplay between sarcopenia and osteoporosis. More future studies are required to investigate the exact regulatory roles of Wnts in muscle-bone crosstalk in musculoskeletal disease models such as sarcopenia and osteoporosis.</p></div><div><h3>Translational potential of this article</h3><p>The systematic review provides an extensive overview to reveal the roles of Wnt/β-catenin signaling pathways in muscle-bone crosstalk. These results provide novel research directions to further understand the underlying mechanism of sarcopenia, osteoporosis, and their crosstalk, finally helping the future development of new therapeutic interventions.</p></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"47 ","pages":"Pages 63-73"},"PeriodicalIF":5.9,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214031X24000512/pdfft?md5=f3cbfd88e7b6e8b5ad75a45029ff52ca&pid=1-s2.0-S2214031X24000512-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141435033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Three-dimensional distribution of subchondral fracture lines in osteonecrosis of the femoral head","authors":"Yan-Bin Wu ,&nbsp;Guang-Bo Liu ,&nbsp;Huo Li ,&nbsp;Jia-Zhou Wu ,&nbsp;Jin-Shu Tang ,&nbsp;Jian-Ting Ye ,&nbsp;Ying-Jie Xiong ,&nbsp;Xi-Wei Peng ,&nbsp;Ze-Xian Liu ,&nbsp;Yu-Zheng Lu ,&nbsp;Cong-Cong Guan ,&nbsp;Hao-Ye Meng ,&nbsp;Xiao-Han Sun ,&nbsp;Xin Wang ,&nbsp;Ai-Yuan Wang ,&nbsp;Zhe Zhao ,&nbsp;Yuan Hu ,&nbsp;Yu-Feng Liu ,&nbsp;Li-Jun Sun ,&nbsp;Ling Qin ,&nbsp;Jiang Peng","doi":"10.1016/j.jot.2024.06.004","DOIUrl":"https://doi.org/10.1016/j.jot.2024.06.004","url":null,"abstract":"<div><h3>Objective</h3><p>To investigate the characteristics of three-dimensional distribution of subchondral fracture lines on the surface of the osteonecrosis femoral head, and to discuss the underlying mechanisms that contribute to its collapse.</p></div><div><h3>Methods</h3><p>We retrospectively analyzed computed tomography (CT) images from 75 patients (comprising a total of 77 femoral heads) diagnosed with Association Research Circulation Osseous (ARCO) stage IIIA or IIIB femoral head necrosis. The three-dimensional structures of both the femoral head and the subchondral fracture line were reconstructed and subsequently fitted into normal femoral head model. A heat map of fracture line was generated to visualize its spatial distribution across the femoral heads surface.to observe its distribution. In addition to that, the femoral head was partitioned into four zones, and the frequency of each fracture line traversing different zones was calculated and analysed.</p></div><div><h3>Results</h3><p>Highest and lowest density of subchondral fracture lines was demonstrated in anterolateral and posterolateral zone respectively. and most sparse in posterolateral. Furthermore, the three-dimensional heat map of fracture lines highlighted their most frequent occurrence in the anterolateral area, particularly near the junction of the femoral head and neck. One fracture line may pass through multiple areas, passage frequencies for fracture lines was observed in zones I, II, III and IV for 66 times (85.7 %), 52 times (67.5 %), 25 times (32.5 %) and 46 times (59.7 %), respectively, with a significant difference between zone I and other zones (P &lt; 0.001).</p></div><div><h3>Conclusion</h3><p>Subchondral fracture line of femoral head occurs most frequently in anterolateral femoral head, suggesting that the anterolateral part may be the initial location of collapse.</p></div><div><h3>Translational potential of this article</h3><p>We found that the subchondral fracture line was most frequently located anterolateral to the femoral head, suggesting that this may be the site of initiation of collapse. Furthermore, we propose an innovative method for analyzing and visualizing subchondral fracture distribution in femoral head necrosis in the form of fracture line heat maps. By doing so, we provide a valuable reference for physicians, enabling them to enhance their management strategies for femoral head necrosis. Ultimately, this approach holds the promise of significantly improving the prognosis and outcomes for patients afflicted with this condition.</p></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"47 ","pages":"Pages 97-104"},"PeriodicalIF":5.9,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214031X24000524/pdfft?md5=7d851c5890e5156b30d86cd1272ec2d9&pid=1-s2.0-S2214031X24000524-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141435087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sclerostin inhibition in rare bone diseases: Molecular understanding and therapeutic perspectives","authors":"Tao Xiaohui ,&nbsp;Luyao Wang ,&nbsp;Xin Yang ,&nbsp;Hewen Jiang ,&nbsp;Ning Zhang ,&nbsp;Huarui Zhang ,&nbsp;Dijie Li ,&nbsp;Xiaofei Li ,&nbsp;Yihao Zhang ,&nbsp;Shenghang Wang ,&nbsp;Chuanxin Zhong ,&nbsp;Sifan Yu ,&nbsp;Meishen Ren ,&nbsp;Meiheng Sun ,&nbsp;Nanxi Li ,&nbsp;Tienan Chen ,&nbsp;Yuan Ma ,&nbsp;Fangfei Li ,&nbsp;Jin Liu ,&nbsp;Yuanyuan Yu ,&nbsp;Ge Zhang","doi":"10.1016/j.jot.2024.05.004","DOIUrl":"https://doi.org/10.1016/j.jot.2024.05.004","url":null,"abstract":"&lt;div&gt;&lt;p&gt;Sclerostin emerges as a novel target for bone anabolic therapy in bone diseases. Osteogenesis imperfecta (OI) and X-linked hypophosphatemia (XLH) are rare bone diseases in which therapeutic potential of sclerostin inhibition cannot be ignored. In OI, genetic/pharmacologic sclerostin inhibition promoted bone formation of mice, but responses varied by genotype and age. Serum sclerostin levels were higher in young OI-I patients, while lower in adult OI-I/III/IV. It's worth investigating whether therapeutic response of OI to sclerostin inhibition could be clinically predicted by genotype and age. In XLH, preclinical/clinical data suggested factors other than identified FGF23 contributing to XLH. Higher levels of circulating sclerostin were detected in XLH. Sclerostin inhibition promoted bone formation in &lt;em&gt;Hyp&lt;/em&gt; mice, while restored phosphate homeostasis in age-/gender-dependent manner. The role of sclerostin in regulating phosphate metabolism deserves investigation. Sclerostin/FGF23 levels of XLH patients with/without response to FGF23-antibody warrants study to develop precise sclerostin/FGF23 inhibition strategy or synergistic/additive strategy. Notably, OI patients were associated with cardiovascular abnormalities, so were XLH patients receiving conventional therapy. Targeting sclerostin loop3 promoted bone formation without cardiovascular risks. Further, blockade of sclerostin loop3-LRP4 interaction while preserving sclerostin loop2-ApoER2 interaction could be a potential precise sclerostin inhibition strategy for OI and XLH with cardiovascular safety.&lt;/p&gt;&lt;p&gt;The Translational Potential of this Article.&lt;/p&gt;&lt;p&gt;Preclinical data on the molecular understanding of sclerostin inhibition in OI and therapeutic efficacy in mouse models of different genotypes, as well as clinical data on serum sclerostin levels in patients with different phenotypes of OI, were reviewed and discussed. Translationally, it would facilitate to develop clinical prediction strategies (e.g. based on genotype and age, not just phenotype) for OI patients responsive to sclerostin inhibition. Both preclinical and clinical data suggested sclerostin as another factor contributing to XLH, in addition to the identified FGF23. The molecular understanding and therapeutic effects of sclerostin inhibition on both promoting bone anabolism and improving phosphate homostasis in &lt;em&gt;Hyp&lt;/em&gt; mice were reviewed and discussed. Translationaly, it would facilitate the development of precise sclerostin/FGF23 inhibition strategy or synergistic/additive strategy for the treatment of XLH. Cardiovascular risk could not be ruled out during sclerostin inhibition treatment, especially for OI and XLH patients with cardiovascular diseases history and cardiovascular abnormalities. Studies on the role of sclerostin in inhiting bone formation and protecting cardiovascular system were reviewed and discussed. Translationaly, blockade of sclerostin loop3-LRP4 interaction while preserving sclerostin loo","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"47 ","pages":"Pages 39-49"},"PeriodicalIF":6.6,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214031X24000469/pdfft?md5=8db4eba1898d809ec16c11a6e3da0a08&pid=1-s2.0-S2214031X24000469-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141429415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Four-year comparative analysis of return to sport and psychological recovery following ACL revision: Artificial ligament vs. anterior tibial tendon allograft","authors":"Tianwu Chen ,&nbsp;Yu Dong ,&nbsp;Yunxia Li ,&nbsp;Shiyi Chen","doi":"10.1016/j.jot.2024.05.003","DOIUrl":"https://doi.org/10.1016/j.jot.2024.05.003","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;p&gt;Research on return to sport and psychological recovery in anterior cruciate ligament (ACL) revision remains scarce. The clinical efficacy of artificial ligament in ACL revision requires further exploration. Our objectives were (1) to compare the midterm clinical outcomes of artificial ligament versus allogenic tendon graft in ACL revision and (2) to analyze the effects of employing artificial ligament on return to sport and psychological recovery in ACL revision.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;p&gt;This cohort study included the cases receiving ACL revision from 2014 to 2021 in Sports Medicine Department of Huashan Hospital. The grafts used were Ligament Advanced Reinforcement System (LARS) and ATT allograft. We recorded patients' baseline data. The final follow-up assessment included subjective scales, physical examination, and return to sport status. We recorded the rates and timings of return to sport. Subjective scales included the 2000 International Knee Documentation Committee (IKDC) subjective score, Lysholm Knee Scaling Score (LKSS), Knee injury and Osteoarthritis Outcome Score (KOOS), Tegner activity score, Marx activity rating score, and Anterior Cruciate Ligament-Return to Sport after Injury (ACL-RSI). Anterior knee stability was assessed using the KT-1000 arthrometer.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;p&gt;Fifty cases (LARS group: 27; ATT group: 23) enrolled and 45 (LARS group: 23; ATT group: 22) completed evaluations with a median follow-up period of 49 months. At recent follow-up, LARS group outperformed in knee stability (1.0 ± 1.9 mm vs. 2.6 ± 3.0 mm, P = 0.039), confidence (86.7 ± 12.4 vs. 69.4 ± 18.6, P &lt; 0.001), emotion (82.7 ± 11.3 vs. 70.7 ± 16.2, P &lt; 0.001), KOOS knee function (78.7 ± 8.8 vs. 69.5 ± 11.0, P = 0.003), quality of life (79.1 ± 16.1 vs. 66.4 ± 19.5, P = 0.014), Tegner score (6.3 ± 1.9 vs. 5.2 ± 2.1, P &lt; 0.001), and Marx activity score (10.7 ± 3.7 vs. 7.9 ± 4.0, P = 0.012). The LARS group had significantly higher return rates: recreational (91.3 % vs. 63.6 %, P = 0.026), knee cutting and pivoting (87.0 % vs. 59.1 %, P = 0.035), competitive (78.3 % vs. 45.5 %, P = 0.023), and pre-injury (56.5 % vs. 27.3 %, P = 0.047). For return timings, the LARS group was earlier at recreational (11.2 ± 3.9 vs. 27.8 ± 9.0 weeks, P &lt; 0.001), knee cutting and pivoting (17.2 ± 5.8 vs. 35.6 ± 13.8 weeks, P &lt; 0.001), competitive (24.8 ± 16.2 vs. 53.2 ± 22.0 weeks, P &lt; 0.001), and pre-injury levels (32.8 ± 11.0 vs. 72.8 ± 16.9 weeks, P &lt; 0.001).&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;p&gt;In ACL revision, using LARS demonstrated improved joint stability and functionality compared to using allogenic ATT four years postoperative. Patients accepting the LARS procedure exhibited higher rates and earlier timings of return to various levels of sport, indicating enhanced confidence and emotional resilience.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;The translational potential of this article&lt;/h3&gt;&lt;p&gt;In ACL revision, the choice of artifi","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"47 ","pages":"Pages 29-38"},"PeriodicalIF":6.6,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214031X24000457/pdfft?md5=9052757f99c9acb29a5fb13d9254c1d8&pid=1-s2.0-S2214031X24000457-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141424004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"XAF1 promotes osteoclast apoptosis by antagonizing the XIAP-caspase axis","authors":"Mingchao Zhang ,&nbsp;Yingkang Huang ,&nbsp;Jinyu Bai ,&nbsp;Wushuang Xu ,&nbsp;Huajian Shan ,&nbsp;Lei Sheng ,&nbsp;Xiang Gao ,&nbsp;Yu Han ,&nbsp;Shiyou Wang ,&nbsp;Chaowen Bai ,&nbsp;Bo Tian ,&nbsp;Yichao Ni ,&nbsp;Qirong Dong ,&nbsp;Feng Ma ,&nbsp;Xiaozhong Zhou","doi":"10.1016/j.jot.2024.05.001","DOIUrl":"https://doi.org/10.1016/j.jot.2024.05.001","url":null,"abstract":"<div><h3>Background</h3><p>Over-activated osteoclast (OC) is a major cause of diseases related to bone loss and bone metabolism. Both bone resorption inhibition and apoptosis induction of osteoclast are crucial in treating these diseases. <em>X-linked inhibitor of apoptosis protein (XIAP)-associated factor 1 (XAF1)</em> is an important interferon-stimulated and apoptotic gene. However, how <em>XAF1</em> regulates bone formation and remodeling is unknown.</p></div><div><h3>Methods</h3><p>We generate global and chimeric <em>Xaf1</em> knockout mouse models and utilize these models to explore the function and mechanism of <em>XAF1</em> in regulating bone formation and remodeling <em>in vivo</em> and <em>in vitro</em>.</p></div><div><h3>Results</h3><p>We show that <em>XAF1</em> depletion enhances osteoclast generation <em>in vitro</em>. <em>XAF1</em> knockout increases osteoclast number and bone resorption, thereby exacerbating bone loss in both OVX and osteolysis models. Activation of XAF1 with BV6 (a potent XIAP inhibitor) suppresses osteoclast formation. Mechanistically, <em>XAF1</em> deletion decreases osteoclast apoptosis by facilitating the interaction between XIAP and caspase-3/7.</p></div><div><h3>Conclusions</h3><p>Our data illustrates an essential role of <em>XAF1</em> in controlling osteoclastogenesis in both osteoporosis and osteolysis mouse models and highlights its underlying mechanism, indicating a potential role in clinical treatment.</p><p>The translational potential of this article: The translation potential of this article is that we first indicated that osteoclast apoptosis induced by XAF1 contribute to the progression of osteoporosis and osteolysis, which provides a novel strategy in the prevention of osteoporosis and osteolysis.</p></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"47 ","pages":"Pages 15-28"},"PeriodicalIF":6.6,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214031X24000433/pdfft?md5=9925a3ade1d74d3c09b11c4dc3d90f2c&pid=1-s2.0-S2214031X24000433-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141290335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An innovative intramedullary bone graft harvesting concept as a fundamental component of scaffold-guided bone regeneration: A preclinical in vivo validation","authors":"Markus Laubach ,&nbsp;Buddhi Herath ,&nbsp;Sinduja Suresh ,&nbsp;Siamak Saifzadeh ,&nbsp;Bronwin L. Dargaville ,&nbsp;Silvia Cometta ,&nbsp;Victoria Schemenz ,&nbsp;Marie-Luise Wille ,&nbsp;Jacqui McGovern ,&nbsp;Dietmar W. Hutmacher ,&nbsp;Flavia Medeiros Savi ,&nbsp;Nathalie Bock","doi":"10.1016/j.jot.2024.05.002","DOIUrl":"https://doi.org/10.1016/j.jot.2024.05.002","url":null,"abstract":"<div><h3>Background</h3><p>The deployment of bone grafts (BGs) is critical to the success of scaffold-guided bone regeneration (SGBR) of large bone defects. It is thus critical to provide harvesting devices that maximize osteogenic capacity of the autograft while also minimizing graft damage during collection. As an alternative to the Reamer-Irrigator-Aspirator 2 (RIA 2) system – the gold standard for large-volume graft harvesting used in orthopaedic clinics today – a novel intramedullary BG harvesting concept has been preclinically introduced and referred to as the ARA (aspirator + reaming-aspiration) concept. The ARA concept uses aspiration of the intramedullary content, followed by medullary reaming-aspiration of the endosteal bone. This concept allows greater customization of BG harvesting conditions vis-à-vis the RIA 2 system. Following its successful <em>in vitro</em> validation, we hypothesized that an ARA concept-collected BG would have comparable <em>in vivo</em> osteogenic capacity compared to the RIA 2 system-collected BG.</p></div><div><h3>Methods</h3><p>We used 3D-printed, medical-grade polycaprolactone-hydroxyapatite (mPCL-HA, wt 96 %:4 %) scaffolds with a Voronoi design, loaded with or without different sheep-harvested BGs and tested them in an ectopic bone formation rat model for up to 8 weeks.</p></div><div><h3>Results</h3><p>Active bone regeneration was observed throughout the scaffold-BG constructs, particularly on the surface of the bone chips with endochondral bone formation, and highly vascularized tissue formed within the fully interconnected pore architecture. There were no differences between the BGs derived from the RIA 2 system and the ARA concept in new bone volume formation and in compression tests (Young's modulus, <em>p</em> = 0.74; yield strength, <em>p</em> = 0.50). These results highlight that the osteogenic capacities of the mPCL-HA Voronoi scaffold loaded with BGs from the ARA concept and the RIA 2 system are equivalent.</p></div><div><h3>Conclusion</h3><p>In conclusion, the ARA concept offers a promising alternative to the RIA 2 system for harvesting BGs to be clinically integrated into SGBR strategies.</p></div><div><h3>The translational potential of this article</h3><p>Our results show that biodegradable composite scaffolds loaded with BGs from the novel intramedullary harvesting concept and the RIA 2 system have equivalent osteogenic capacity. Thus, the innovative, highly intuitive intramedullary harvesting concept offers a promising alternative to the RIA 2 system for harvesting bone grafts, which are an important component for the routine translation of SGBR concepts into clinical practice.</p></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"47 ","pages":"Pages 1-14"},"PeriodicalIF":6.6,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214031X24000445/pdfft?md5=2d40fa4e7544cfe5b3ab7ef9d3fde317&pid=1-s2.0-S2214031X24000445-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141249472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sipeimine ameliorates osteoarthritis progression by suppression of NLRP3 inflammasome-mediated pyroptosis through inhibition of PI3K/AKT/NF-κB pathway: An in vitro and in vivo study","authors":"Yuqin Fang ,&nbsp;Chao Lou ,&nbsp;Junlei Lv ,&nbsp;Chaoyang Zhang ,&nbsp;Ziteng Zhu ,&nbsp;Wei Hu ,&nbsp;Hua Chen ,&nbsp;Liaojun Sun ,&nbsp;Wenhao Zheng","doi":"10.1016/j.jot.2024.04.004","DOIUrl":"https://doi.org/10.1016/j.jot.2024.04.004","url":null,"abstract":"<div><h3>Background</h3><p>Osteoarthritis (OA) is a chronic and degenerative condition that persists and progresses over time. Sipeimine (Sip), a steroidal alkaloid derived from <em>Fritillariae Cirrhosae Bulbus</em>, has attracted considerable attention due to its exceptional anti-inflammatory, analgesic, antioxidant, and anti-cancer characteristics. However, Sip's effects on OA and its mechanism still need further research.</p></div><div><h3>Methods</h3><p>This study utilized network pharmacology to identify initial targets for Sip. Functional associations of Sip in OA were clarified through Gene Ontology (GO) enrichment analysis, bioinformatically analyzing a list of targets. Subsequently, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis assessed pathways linked to Sip's therapeutic efficacy in OA. Molecular docking techniques explored Sip's binding affinity with key targets. In vitro experiments assessed Sip's impact on lipopolysaccharide (LPS)-induced pro-inflammatory factors and its protective effects on collagen-II and aggrecan degradation within the extracellular matrix (ECM). Western blotting and fluorescence analyses were conducted to determine Sip-mediated signaling pathways. Moreover, in vivo experiments using a mouse OA model validated Sip's therapeutic efficacy.</p></div><div><h3>Results</h3><p>The results from network pharmacology revealed a total of 57 candidate targets for Sip in OA treatment. GO enrichment analysis demonstrated a robust correlation between Sip and inflammatory response, response to LPS and NF-κB-inducing kinase activity in OA. KEGG enrichment analysis highlighted the significance of NF-κB and PI3K-AKT pathways in Sip's therapeutic potential for OA. Furthermore, molecular docking results demonstrated Sip's robust binding affinity with p65 and PI3K. In vitro experiments demonstrated Sip's effectively suppressed the expression of pro-inflammatory factors induced by LPS, such as COX-2, iNOS, IL-1β, and IL-18. Besides, Sip counteracted the degradation of collagen-II and aggrecan within the ECM and the expression of MMP-13 and ADAMTS-5 mediated by LPS. The safeguarding effects of Sip were ascribed to its inhibition of PI3K/AKT/NF-κB pathway and NLRP3 inflammasome mediated pyroptosis. Additionally, in vivo experiments revealed that Sip could alleviate the subchondral remodeling, cartilage degeneration, synovitis as well as ECM degradation a mouse model of OA.</p></div><div><h3>Conclusion</h3><p>Sip exhibited potential in attenuating OA progression by suppressing the PI3K/AKT/NF-κB pathway, consequently inhibiting the activation of NLRP3 inflammasome and pyroptosis.</p></div><div><h3>The translational potential statement</h3><p>The translational potential of this articleThis study provides a biological rationale for the use of Sip as a potential candidate for OA treatment, provide a new concept for the cartilage targeted application of natural compounds.</p></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"46 ","pages":"Pages 1-17"},"PeriodicalIF":6.6,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214031X2400041X/pdfft?md5=1359d7b076e48765a52220bf060fe590&pid=1-s2.0-S2214031X2400041X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140893301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}