Journal of Orthopaedic Translation最新文献

{"title":"Hyperbaric oxygen promotes bone regeneration by activating the mechanosensitive Piezo1 pathway in osteogenic progenitors","authors":"","doi":"10.1016/j.jot.2024.07.001","DOIUrl":"10.1016/j.jot.2024.07.001","url":null,"abstract":"<div><h3>Background</h3><p>Hyperbaric oxygen (HBO) therapy is widely used to treat bone defects, but the correlation of high oxygen concentration and pressure to osteogenesis is unclear.</p></div><div><h3>Methods</h3><p>Bilateral monocortical tibial defect surgeries were performed on 12-week-old Prrx1-Cre; Rosa26-tdTomato and Prrx1-Cre; Piezo1^fl/+ mice. Daily HBO treatment was applied on post-surgery day (PSD) 1–9; and daily mechanical loading on tibia was from PSD 5 to 8. The mice were euthanized on PSD 10, and bone defect repair in their tibias was evaluated using μCT, biomechanical testing, and immunofluorescence deep-tissue imaging. The degree of angiogenesis–osteogenesis coupling was determined through spatial correlation analysis. Bone marrow stromal cells from knockout mice were cultured in vitro, and their osteogenic capacities of the cells were assessed. The activation of genes in the Piezo1–YAP pathway was evaluated using RNA sequencing and quantitative real-time polymerase chain reaction.</p></div><div><h3>Results</h3><p>Lineage tracing showed HBO therapy considerably altered the number of Prrx1⁺ cells and their progeny in a healing bone defect. Using conditional knockdown mice, we found that HBO stimulation activates the Piezo1–YAP axis in Prrx1⁺ cells and promotes osteogenesis–angiogenesis coupling during bone repair. The beneficial effect of HBO was similar to that of anabolic mechanical stimulation, which also acts through the Piezo1–YAP axis. Subsequent transcriptome sequencing results revealed that similar mechanosensitive pathways are activated by HBO therapy in a bone defect.</p></div><div><h3>Conclusion</h3><p>HBO therapy promotes bone tissue regeneration through the mechanosensitive Piezo1–YAP pathway in a population of Prrx1⁺ osteogenic progenitors. Our results contribute to the understanding of the mechanism by which HBO therapy treats bone defects.</p></div><div><h3>The Translational Potential of this Article</h3><p>Hyperbaric oxygen therapy is widely used in clinical settings. Our results show that osteogenesis was induced by the activation of the Piezo1–YAP pathway in osteoprogenitors after HBO stimulation, and the underlying mechanism was elucidated. These results may help improve current HBO methods and lead to the formulation of alternative treatments that achieve the same functional outcomes.</p></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214031X2400069X/pdfft?md5=a06cbbc39aea7a87fcba5821eaf62a59&pid=1-s2.0-S2214031X2400069X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141950382","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":"A 3D-printed scaffold composed of Alg/HA/SIS for the treatment of diabetic bone defects","authors":"","doi":"10.1016/j.jot.2024.07.006","DOIUrl":"10.1016/j.jot.2024.07.006","url":null,"abstract":"<div><h3>Background</h3><p>Diabetic bone healing remains a great challenge due to its pathological features including biochemical disturbance, excessive inflammation, and reduced blood vessel formation. In previous studies, small intestine submucosa (SIS) has been demonstrated for its immunomodulatory and angiogenic properties, which are necessary to diabetic bone healing. However, the noticeable drawbacks of SIS such as fast degradation rate, slow gelling time, and weak mechanical property seriously impede the 3D printing of SIS for bone repair.</p></div><div><h3>Method</h3><p>In this study, we developed a novel kind of 3D-printed scaffold composed of alginate, nano-hydroxyapatite, and SIS. The morphological characterization, biocompatibility, and <em>in vitro</em> biological effects of the scaffolds were evaluated, and an established diabetic rat model was used for testing the <em>in vivo</em> biological effect of the scaffold after implantation.</p></div><div><h3>Results</h3><p>The <em>in vitro</em> and <em>in vivo</em> results show that the addition of SIS can tune the immunomodulatory properties and angiogenic and osteogenic performances of 3D-printed scaffold, where the macrophages polarization of M2 phenotype, migration and tube formation of HUVECs, as well as osteogenic expression of ALP, are all improved, which bode well with the functional requirements for treating diabetic bone nonunion. Furthermore, the incorporation of alginate substantially improves the printability of composites with tunable degradation properties, thereby broadening the application prospect of SIS-based materials in the field of tissue engineering.</p></div><div><h3>Conclusion</h3><p>The fabricated 3D-printed Alg/HA/SIS scaffold provides desirable immunomodulatory effect, as well as good osteogenic and angiogenic performances <em>in vitro</em> and <em>in vivo</em>, which properties are well-suited with the requirement for treating diabetic bone defects.</p></div><div><h3>Translational potential of this article</h3><p>The incorporation of SIS and alginate acid not only provides good printability of the newly fabricated 3D-printed Alg/HA/SIS scaffold, but also improves its immunoregulatory and angiogenic properties, which suits well with the requirement for treating diabetic bone disease and opens up new horizons for the development of implants associating diabetic bone healings.</p></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11287068/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141860122","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":"Osteostaticytes: A novel osteoclast subset couples bone resorption and bone formation","authors":"Zhiyuan Wei ,&nbsp;Jian Zhou ,&nbsp;Jie Shen ,&nbsp;Dong Sun ,&nbsp;Tianbao Gao ,&nbsp;Qin Liu ,&nbsp;Hongri Wu ,&nbsp;Xiaohua Wang ,&nbsp;Shulin Wang ,&nbsp;Shiyu Xiao ,&nbsp;Chao Han ,&nbsp;Di Yang ,&nbsp;Hui Dong ,&nbsp;Yuzhang Wu ,&nbsp;Yi Zhang ,&nbsp;Shuai Xu ,&nbsp;Xian Wang ,&nbsp;Jie Luo ,&nbsp;Qijie Dai ,&nbsp;Jun Zhu ,&nbsp;Zhao Xie","doi":"10.1016/j.jot.2024.06.010","DOIUrl":"https://doi.org/10.1016/j.jot.2024.06.010","url":null,"abstract":"<div><h3>Background</h3><p>Osteomyelitis (OM) is an inflammatory condition of bone characterized by cortical bone devascularization and necrosis. Dysregulation of bone remodelling is triggered by OM. Bone remodelling is precisely coordinated by bone resorption and formation via a reversal phase. However, the cellular and molecular mechanisms underlying bone remodelling failure after osteomyelitis remain elusive.</p></div><div><h3>Methods</h3><p>To elucidate the cellular and molecular mechanism underlying bone healing after osteomyelitis, we employed single-cell RNA sequencing (scRNA-seq) to depict the atlas of human cortical bone in normal, infected and reconstructed states. Dimensionality reduction by t-stochastic neighbourhood embedding (t-SNE) and graph-based clustering were applied to analyse the detailed clusters of osteoclast lineages. After trajectory analysis of osteoclast lineages over pseudotime, real-time PCR and immunofluorescence (IF) staining were applied to identify marker gene expression of various osteoclast lineages in the osteoclast induction model and human bone sections, respectively. The potential function and communication of osteoclasts were analysed via gene set enrichment analysis (GSEA) and CellChat. The chemotactic ability of mesenchymal stem cells (MSCs) and osteoclast lineage cells in various differentiation states was determined by transwell assays and coculture assays. The effects of various osteoclast lineages on the osteogenic differentiation potential of MSCs were also determined by using this coculture system. A normal mouse tibia fracture model and an osteomyelitis-related tibia fracture model were generated via injection of luciferase-labelled <em>Staphylococcus aureus</em> to verify the relationships between a novel osteoclast lineage and MSCs. Then, the infection was detected by a bioluminescence imaging system. Finally, immunofluorescence staining was used to detect the expression of markers of MSCs and novel osteoclast lineages in different remodelling phases in normal and infected bone remodelling models.</p></div><div><h3>Results</h3><p>In this study, we constructed a cell atlas encompassing normal, infected, and reconstructed cortical bone. Then, we identified a novel subset at the earlier stage of the osteoclast lineage that exhibited increased expression of IDO1, CCL3, and CCL4. These IDO1^highCCL3^highCCL4^high cells, termed osteostaticytes (OSCs), were further regarded as the reservoir of osteoclasts in the reversal phase. Notably, OSCs exhibited the highest chemotactic activity, surpassing other lineage subsets. We also discovered that cells at the earlier stage of the osteoclast lineage play a significant role in recruiting mesenchymal stem cells (MSCs). Finally, the data revealed that OSCs might be positively related to the occurrence of bone MSCs and the contribution of bone remodelling.</p></div><div><h3>Conclusion</h3><p>Collectively, our findings revealed a nove","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214031X24000639/pdfft?md5=bdb204ccae657e06dcbcdb9506fa69ff&pid=1-s2.0-S2214031X24000639-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141479177","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":"Roles of Sp7 in osteoblasts for the proliferation, differentiation, and osteocyte process formation","authors":"Qing Jiang ,&nbsp;Kenichi Nagano ,&nbsp;Takeshi Moriishi ,&nbsp;Hisato Komori ,&nbsp;Chiharu Sakane ,&nbsp;Yuki Matsuo ,&nbsp;Zhiguo Zhang ,&nbsp;Riko Nishimura ,&nbsp;Kosei Ito ,&nbsp;Xin Qin ,&nbsp;Toshihisa Komori","doi":"10.1016/j.jot.2024.06.005","DOIUrl":"https://doi.org/10.1016/j.jot.2024.06.005","url":null,"abstract":"<div><h3>Background</h3><p>Zinc finger-containing transcription factor Osterix/Specificity protein-7 (Sp7) is an essential transcription factor for osteoblast differentiation. However, its functions in differentiated osteoblasts remain unclear and the effects of osteoblast-specific <em>Sp7</em> deletion on osteocytes have not been sufficiently studied.</p></div><div><h3>Methods</h3><p><em>Sp7</em>^{floxneo/floxneo} mice, in which <em>Sp7</em> expression was 30 % of that in wild-type mice because of disturbed splicing by neo gene insertion, and osteoblast-specific knockout (<em>Sp7</em>^{fl/fl;<em>Col1a1</em>−Cre}) mice using 2.3-kb <em>Col1a1</em> enhanced green fluorescent protein (EGFP)-Cre were examined by micro-computed tomography (micro-CT), bone histomorphometry, serum markers, and histological analyses. The expression of osteoblast and osteocyte marker genes was examined by real-time reverse transcription (RT)-PCR analysis. Osteoblastogenesis, osteoclastogenesis, and regulation of the expression of collagen type I alpha 1 chain (<em>Col1a1</em>) were examined in primary osteoblasts.</p></div><div><h3>Results</h3><p>Femoral trabecular bone volume was higher in female <em>Sp7</em>^{floxneo/floxneo} and <em>Sp7</em>^{fl/fl;<em>Col1a1</em>−Cre} mice than in the respective controls, but not in males. Bromodeoxyuridine (BrdU)-positive osteoblastic cells were increased in male <em>Sp7</em>^{fl/fl;<em>Col1a1</em>−Cre} mice, and osteoblast number and the bone formation rate were increased in tibial trabecular bone in female <em>Sp7</em>^{fl/fl;<em>Col1a1</em>−Cre} mice, although osteoblast maturation was inhibited in female <em>Sp7</em>^{fl/fl;<em>Col1a1</em>−Cre} mice as shown by the increased expression of an immature osteoblast marker gene, secreted phosphoprotein 1 (<em>Spp1</em>), and reduced expression of a mature osteoblast marker gene, bone gamma-carboxyglutamate protein/bone gamma-carboxyglutamate protein 2 (<em>Bglap/Bglap2</em>). Furthermore, alkaline phosphatase activity was increased but mineralization was reduced in the culture of primary osteoblasts from <em>Sp7</em>^{fl/fl;<em>Col1a1</em>−Cre} mice. Therefore, the accumulated immature osteoblasts in <em>Sp7</em>^{fl/fl;<em>Col1a1</em>−Cre} mice was likely compensated for the inhibition of osteoblast maturation at different levels in males and females. Vertebral trabecular bone volume was lower in both male and female <em>Sp7</em>^{fl/fl;<em>Col1a1</em>−Cre} mice than in the controls and the osteoblast parameters and bone formation rate in females were lower in <em>Sp7</em>^{fl/fl;<em>Col1a1</em>−Cre} mice than in <em>Sp7</em>^fl/fl mice, suggesting differential regulatory mechanisms in long bones and vertebrae. The femoral cortical bone was thin and porous in <em>Sp7</em>^{floxneo/floxneo} and <em>Sp7</em>^{fl/fl;<em>Col1a1</em>−Cre} mice of both sexes, the number of can","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214031X24000536/pdfft?md5=fcf3b3db8cc860edc417dcaa8f83f032&pid=1-s2.0-S2214031X24000536-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141479178","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":"Localized delivery of metformin via 3D printed GelMA-Nanoclay hydrogel scaffold for enhanced treatment of diabetic bone defects","authors":"Hetong Li ,&nbsp;Beini Mao ,&nbsp;Jintao Zhong,&nbsp;Xiuwang Li,&nbsp;Hongxun Sang","doi":"10.1016/j.jot.2024.06.013","DOIUrl":"https://doi.org/10.1016/j.jot.2024.06.013","url":null,"abstract":"<div><h3>Background</h3><p>Diabetic bone defects present significant challenges for individuals with diabetes. While metformin has been explored for bone regeneration via local delivery, its application in treating diabetic bone defects remains under-explored. In this study, we aim to leverage 3D printing technology to fabricate a GelMA-Nanoclay hydrogel scaffold loaded with metformin specifically for this purpose. The objective is to assess whether the in situ release of metformin can effectively enhance osteogenesis, angiogenesis, and immunomodulation in the context of diabetic bone defects.</p></div><div><h3>Materials and methods</h3><p>Utilizing 3D printing technology, we constructed a GelMA-Nanoclay-Metformin hydrogel scaffold with optimal physical properties and biocompatibility. The osteogenic, angiogenic, and immunomodulatory characteristics of the hydrogel scaffold were thoroughly investigated through both in vitro and in vivo experiments.</p></div><div><h3>Results</h3><p>GelMA10%-Nanoclay8%-Metformin5mg/mL was selected as the bioink for 3D printing due to its favorable swelling rate, degradation rate, mechanical strength, and drug release rate. Through in vitro investigations, the hydrogel scaffold extract, enriched with metformin, demonstrated a substantial enhancement in the proliferation and migration of BMSCs within a high-glucose microenvironment. It effectively enhances osteogenesis, angiogenesis, and immunomodulation. In vivo experimental outcomes further underscored the efficacy of the metformin-loaded GelMA-Nanoclay hydrogel scaffold in promoting superior bone regeneration within diabetic bone defects.</p></div><div><h3>Conclusions</h3><p>In conclusion, while previous studies have explored local delivery of metformin for bone regeneration, our research is pioneering in its application to diabetic bone defects using a 3D printed GelMA-Nanoclay hydrogel scaffold. This localized delivery approach demonstrates significant potential for enhancing bone regeneration in diabetic patients, offering a novel approach for treating diabetic bone defects.</p></div><div><h3>The translational potential of this article</h3><p>Our study demonstrates, for the first time, the successful loading of the systemic antidiabetic drug metformin onto a hydrogel scaffold for localized delivery. This approach exhibits significant efficacy in mending diabetic bone defects, presenting a promising new avenue for the treatment of such conditions.</p></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214031X24000664/pdfft?md5=49e870b4d7434a75f558a1352e15d3ca&pid=1-s2.0-S2214031X24000664-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141542541","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":"Understanding pathophysiology and injury mechanisms is the foundation for invention/innovation and clinical translation in orthopaedics","authors":"","doi":"10.1016/j.jot.2024.07.003","DOIUrl":"10.1016/j.jot.2024.07.003","url":null,"abstract":"","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214031X24000718/pdfft?md5=c0520133f484f6ac36c367d5f097c670&pid=1-s2.0-S2214031X24000718-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141692130","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":"Sargassum polysaccharide attenuates osteoarthritis in rats and is associated with the up-regulation of the ITGβ1-PI3K-AKT signaling pathway","authors":"Yanzhi Liu ,&nbsp;Rui Lin ,&nbsp;Haiping Fang ,&nbsp;Lixian Li,&nbsp;Min Zhang,&nbsp;Lujiao Lu,&nbsp;Xiang Gao,&nbsp;Jintong Song,&nbsp;Jinsong Wei,&nbsp;Qixian Xiao,&nbsp;Fucheng Zhang,&nbsp;Kefeng Wu,&nbsp;Liao Cui","doi":"10.1016/j.jot.2024.06.015","DOIUrl":"https://doi.org/10.1016/j.jot.2024.06.015","url":null,"abstract":"<div><h3>Background</h3><p>Osteoarthritis (OA) presents a formidable challenge, characterized by as-yet-unclear mechanical intricacies within cartilage and the dysregulation of bone homeostasis. Our preliminary data revealed the encouraging potential of a Sargassum polysaccharide (SP), in promoting chondrogenesis. The aim of our study is to comprehensively assess the therapeutic effects of SP on OA models and further elucidate its potential mechanism.</p></div><div><h3>Methods</h3><p>The protective effects of SP were initially evaluated in an inflammation-induced human chondrocyte (C28) cell model. CCK-8 assays, Alcian blue staining, RT-qPCR and Western blotting were used to verify the chondrogenesis of SP <em>in vitro</em>. To assess the efficacy of SP <em>in vivo</em>, surgically induced medial meniscus destabilization (DMM) OA rats underwent an 8-week SP treatment. The therapeutic effects of SP in OA rats were comprehensively evaluated using X-ray imaging, micro-computed tomography (μ-CT), histopathological analysis, as well as immunohistochemical and immunofluorescent staining. Following these assessments, we delved into the potential signaling pathways of SP in inflammatory chondrocytes utilizing RNA-seq analysis. Validation of these findings was conducted through RT-qPCR and western blotting techniques.</p></div><div><h3>Results</h3><p>SP significantly enhance the viability of C28 chondrocytes, and increased the secretion of acidic glycoproteins. Moreover, SP stimulated the expression of chondrogenic genes (<em>Aggrecan</em>, <em>Sox9</em>, <em>Col2a1</em>) and facilitated the synthesis of Collagen II protein in C28 inflammatory chondrocytes. <em>In vivo</em> experiments revealed that SP markedly ameliorated knee joint stenosis, alleviated bone and cartilage injuries, and reduced the histopathological scores in the OA rats. μ-CT analysis confirmed that SP lessened bone impairments in the medial femoral condyle and the subchondral bone of the tibial plateau, significantly improving the microarchitectural parameters of the subchondral bone. Histopathological analyses indicated that SP notably enhanced cartilage quality on the surface of the tibial plateau, leading to increased cartilage thickness and area. Immunohistochemistry staining and immunofluorescence staining corroborated these findings by showing a significant promotion of Collagen II expression in OA joints treated with SP. RNA-seq analysis suggest that SP's effects were mediated through the regulation of the ITGβ1-PI3K-AKT signaling axis, thereby stimulating chondrogenesis. Verification through RT-qPCR and Western blot analyses confirmed that SP significantly upregulated the expression of ITGβ1, p110δ, AKT1, ACAN, and Col2a1. Notably, knock-down of ITGβ1 using siRNA in C28 chondrocytes inhibited the expression of ITGβ1, p110δ, AKT1, and ACAN. However, these inhibitory effects were not completely reversed by supplemental SP intervention.</p></div><div><h3>Conclusions</h3><p>In summa","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214031X24000688/pdfft?md5=905d0e6e261956eb4fc78c0c67b50af4&pid=1-s2.0-S2214031X24000688-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141478373","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":"Functionally improved mesenchymal stem cells via nanosecond pulsed electric fields for better treatment of osteoarthritis","authors":"Jianjing Lin ,&nbsp;Kejia Li ,&nbsp;Zhen Yang ,&nbsp;Fuyang Cao ,&nbsp;Liang Gao ,&nbsp;Tong Ning ,&nbsp;Dan Xing ,&nbsp;Hui Zeng ,&nbsp;Qiang Liu ,&nbsp;Zigang Ge ,&nbsp;Jianhao Lin","doi":"10.1016/j.jot.2024.03.006","DOIUrl":"https://doi.org/10.1016/j.jot.2024.03.006","url":null,"abstract":"<div><h3>Background</h3><p>Numerous approaches have been utilized to optimize mesenchymal stem cells (MSCs) performance in treating osteoarthritis (OA), however, the constrained diminished activity and chondrogenic differentiation capacity impede their therapeutic efficacy. Previous investigations have successfully shown that pretreatment with nanosecond pulsed electric fields (nsPEFs) significantly enhances the chondrogenic differentiation of MSCs. Therefore, this study aims to explore nsPEFs as a strategy to improve OA therapy by enhancing MSCs' activity and chondrogenic differentiation and also investigate its potential mechanism.</p></div><div><h3>Methods</h3><p>In this study, a million MSCs were carefully suspended within a 0.4-cm gap cuvette and subjected to five pulses of nsPEFs (100 ns at 10 kV/cm, 1 Hz), with a 1-s interval between each pulse. A control group of MSCs was maintained without nsPEFs treatment for comparative analysis. nsPEFs were applied to regulate the MSCs performance and hinder OA progresses. In order to further explore the corresponding mechanism, we examined the changes of MSCs transcriptome after nsPEF pretreatment. Finally, we studied the properties of extracellular vesicles (EVs) secreted by MSCs affected by nsPEF and the therapeutic effect on OA.</p></div><div><h3>Results</h3><p>We found that nsPEFs pretreatment promoted MSCs migration and viability, particularly enhancing their viability temporarily <em>in vivo</em>, which is also confirmed by mRNA sequencing analysis. It also significantly inhibited the development of OA-like chondrocytes <em>in vitro</em> and prevented OA progression in rat models. Additionally, we discovered that nsPEFs pretreatment reprogrammed MSC performance by enhancing EVs production (5.77 ± 0.92 folds), and consequently optimizing their therapeutic potential.</p></div><div><h3>Conclusions</h3><p>In conclusion, nsPEFs pretreatment provides a simple and effective strategy for improving the MSCs performance and the therapeutic effects of MSCs for OA. EVs-nsPEFs may serve as a potent therapeutic material for OA and hold promise for future clinical applications.</p></div><div><h3>The translational potential of this article</h3><p>This study indicates that MSCs pretreated by nsPEFs greatly inhibited the development of OA. nsPEFs pretreatment will be a promising and effective method to optimize the therapeutic effect of MSCs in the future.</p></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214031X24000317/pdfft?md5=6ac37a15ef597a795635e5119c89e763&pid=1-s2.0-S2214031X24000317-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141542540","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":"Pyroptosis-related crosstalk in osteoarthritis: Macrophages, fibroblast-like synoviocytes and chondrocytes","authors":"Shida Kuang ,&nbsp;Wen Sheng ,&nbsp;Jiahao Meng ,&nbsp;Weijie Liu ,&nbsp;Yifan Xiao ,&nbsp;Hang Tang ,&nbsp;Xinying Fu ,&nbsp;Min Kuang ,&nbsp;Qinghu He ,&nbsp;Shuguang Gao","doi":"10.1016/j.jot.2024.06.014","DOIUrl":"https://doi.org/10.1016/j.jot.2024.06.014","url":null,"abstract":"<div><p>The pathogenesis of osteoarthritis (OA) involves a multifaceted interplay of inflammatory processes. The initiation of pyroptosis involves the secretion of pro-inflammatory cytokines and has been identified as a critical factor in regulating the development of OA. Upon initiation of pyroptosis, a multitude of inflammatory mediators are released and can be disseminated throughout the synovial fluid within the joint cavity, thereby facilitating intercellular communication across the entire joint. The main cellular components of joints include chondrocytes (CC), fibroblast-like synoviocytes (FLS) and macrophages (MC). Investigating their interplay can enhance our understanding of OA pathogenesis. Therefore, we comprehensively examine the mechanisms underlying pyroptosis and specifically investigate the intercellular interactions associated with pyroptosis among these three cell types, thereby elucidating their collective contribution to the progression of OA. We propose the concept of ' CC-FLS-MC pyroptosis-related crosstalk', describe the various pathways of pyroptotic interactions among these three cell types, and focus on recent advances in intervening pyroptosis in these three cell types for treating OA. We hope this will provide a possible direction for diversification of treatment for OA.</p><p><em>The Translational potential of this article</em>. The present study introduces the concept of ‘MC-FLS-CC pyroptosis-related crosstalk' and provides an overview of the mechanisms underlying pyroptosis, as well as the pathways through which it affects MC, FLS, and CC. In addition, the role of regulation of these three types of cellular pyroptosis in OA has also been concerned. This review offers novel insights into the interplay between these cell types, with the aim of providing a promising avenue for diversified management of OA.</p></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214031X24000676/pdfft?md5=4f6ff77493dd6129278e5fe36664e4af&pid=1-s2.0-S2214031X24000676-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141478879","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":"The impact of copper on bone metabolism","authors":"Zihan Zhang,&nbsp;Huixue Tang,&nbsp;Tingting Du,&nbsp;Di Yang","doi":"10.1016/j.jot.2024.06.011","DOIUrl":"https://doi.org/10.1016/j.jot.2024.06.011","url":null,"abstract":"<div><p>Copper is an essential trace element for the human body. Abnormalities in copper metabolism can lead to bone defects, mainly by directly affecting the viability of osteoblasts and osteoclasts and their bone remodeling function, or indirectly regulating bone metabolism by influencing enzyme activities as cofactors. Copper ions released from biological materials can affect osteoblasts and osteoclasts, either directly or indirectly by modulating the inflammatory response, oxidative stress, and rapamycin signaling. This review presents an overview of recent progress in the impact of copper on bone metabolism.</p><p><strong>Translational potential of this article</strong>: The impact of copper on bone metabolism can provide insights into clinical application of copper-containing supplements and biomaterials.</p></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214031X24000640/pdfft?md5=d4b410a779b781067351b1d704ec562e&pid=1-s2.0-S2214031X24000640-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141479180","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}