Journal of Orthopaedic Translation最新文献

{"title":"Prevalence, risk factors, microbiological results and clinical outcome in unexpected positive intraoperative cultures in unclear and presumed aseptic hip and knee revision arthroplasties – A ten-year retrospective analysis with a minimum follow up of 2 years","authors":"","doi":"10.1016/j.jot.2024.08.002","DOIUrl":"10.1016/j.jot.2024.08.002","url":null,"abstract":"<div><h3>Background</h3><p>The aim of this study was to assess the prevalence, microbiological spectrum, risk factors, and clinical outcomes of unexpected-positive-intraoperative-cultures (UPIC) in presumed aseptic and unclear revision-total-hip-/knee-arthroplasties (rTHA and rTKA) compared to culture-negative (CN) revisions.</p></div><div><h3>Methods</h3><p>This study reviewed all International-consensus-meeting-2018 (ICM 2018) negative or inconclusive rTHA (n = 751) and rTKA (n = 679) performed at our institution from 2011 to 2020 with a minimum follow-up of two years. A Kaplan-Meier-analysis was performed to determine the septic and aseptic-free implant survival in cases with UPIC's and matched culture-negative cases. Patient demographics, risk factors, microbiological spectrum and clinical outcomes were evaluated.</p></div><div><h3>Results</h3><p>There were significantly more UPIC cases in rTHA 196/751 (26.1 %) compared to rTKA 113/679 (16.6 %); (p &lt; 0.001). UPICs in rTKA and rTHA have a lower septic and aseptic implant-free-survival compared to CN revisions. Patients with a history of nickel allergy have a higher risk of an UPIC in rTHA and rTKA (p &lt; 0.001). Septic re-revisions after UPIC had a significantly (H: p = 0.004; K: p = 0.030) shorter time period to the primary/previous surgery (H: 84 (IQR:41–797); K: 115 (IQR:55–446)) compared to patients with aseptic re-revisions after UPIC (H:1248 (IQR:178-3534); K: 827 (IQR:361-1183)).</p></div><div><h3>Conclusion</h3><p>UPICs have a higher rate of septic and aseptic failure than CN outcomes. UPICs are twice as common in rTHA compared to rTKA. Preoperative PJI workup reduces the UPIC rate. Nickel allergy is a risk factor for UPIC. Early revisions with UPICs after primary THA or TKA have a higher risk of septic failure.</p></div><div><h3>The translational potential of this article</h3><p>This article provides new information on revision rates for UPIC and potential risk factors for UPIC and its treatment failure.</p></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214031X24000895/pdfft?md5=60db224076b882de5a10e78430714624&pid=1-s2.0-S2214031X24000895-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141997810","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":"Strontium zinc silicate simultaneously alleviates osteoporosis and sarcopenia in tail-suspended rats via Piezo1-mediated Ca2+ signaling","authors":"","doi":"10.1016/j.jot.2024.07.014","DOIUrl":"10.1016/j.jot.2024.07.014","url":null,"abstract":"<div><h3>Background</h3><p>Long-term physical inactivity probably leads to a co-existence of osteoporosis and sarcopenia which result in a high risk of falls, fractures, disability and even mortality. However, universally applicable and feasible approaches are lacking in the concurrent treatment of osteoporosis and sarcopenia. In this study, we evaluated the effect of strontium zinc silicate bioceramic (SZS) extract on osteoporosis and sarcopenia and explored its underlying mechanisms.</p></div><div><h3>Methods</h3><p>Hindlimb osteoporosis and sarcopenia were established in a tail-suspended rat model. The bones were conducted μCT scanning, histological examination, and gene expression analysis, and the muscles were conducted histological examination and gene expression analysis. <em>In vitro,</em> the effect of SZS extract on osteoblasts was determined by alizarin red S staining, immunofluorescence and qPCR. Similarly, the effect of SZS extract on myoblasts was determined by immunofluorescence and qPCR.. At last, the role of Piezo1 and the change of intracellular calcium ion (Ca²⁺) were explored through blockading the Piezo1 by GsMTx4 in MC3T3-E1 and C2C12 cells, respectively.</p></div><div><h3>Results</h3><p>We found that SZS extract could concurrently and efficiently prevent bone structure deterioration, muscle atrophy and fibrosis in hind limbs of the tail-suspended rats. The <em>in vivo</em> study also showed that SZS extract could upregulate the mRNA expression of Piezo1, thereby maintaining the homeostasis of bones and muscles. <em>In vitro</em> study demonstrated that SZS extract could promote the proliferation and differentiation of MC3T3-E1 and C2C12 cells by increasing the intracellular Ca²⁺ in a Piezo1-dependent manner.</p></div><div><h3>Conclusion</h3><p>This study demonstrated that SZS extract could increase Piezo1-mediated intracellular Ca²⁺, and facilitate osteogenic differentiation of osteoblast and myogenic differentiation of myoblasts, contributing to alleviation of osteoporosis and sarcopenia in a tail-suspended rat model.</p></div><div><h3>The translational potential of this article</h3><p>The current study might provide a universally applicable and efficient strategy to treat musculoskeletal disorders based on bioactive ceramics. The verification of the role of Piezo1-modulated intracellular Ca²⁺ during osteogenesis and myogenesis provided a possible therapeutic target against mechanical related diseases.</p></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214031X24000883/pdfft?md5=108fcca703d7d99942f6d66c0baf037c&pid=1-s2.0-S2214031X24000883-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141979040","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":"Phillygenin inhibits neuroinflammation and promotes functional recovery after spinal cord injury via TLR4 inhibition of the NF-κB signaling pathway","authors":"","doi":"10.1016/j.jot.2024.07.013","DOIUrl":"10.1016/j.jot.2024.07.013","url":null,"abstract":"<div><h3>Background</h3><p>Spinal cord injuries (SCIs) trigger a cascade of detrimental processes, encompassing neuroinflammation and oxidative stress (OS), ultimately leading to neuronal damage. Phillygenin (PHI), isolated from forsythia, is used in a number of biomedical applications, and is known to exhibit anti-neuroinflammation activity. In this study, we investigated the role and mechanistic ability of PHI in the activation of microglia-mediated neuroinflammation and subsequent neuronal apoptosis following SCI.</p></div><div><h3>Methods</h3><p>A rat model of SCI was used to investigate the impact of PHI on inflammation, axonal regeneration, neuronal apoptosis, and the restoration of motor function. <em>In vitro</em>, neuroinflammation models were induced by stimulating microglia with lipopolysaccharide (LPS); then, we investigated the influence of PHI on pro-inflammatory mediator release in LPS-treated microglia along with the underlying mechanisms. Finally, we established a co-culture system, featuring microglia and VSC 4.1 cells, to investigate the role of PHI in the activation of microglia-mediated neuronal apoptosis.</p></div><div><h3>Results</h3><p><em>In vivo</em>, PHI significantly inhibited the inflammatory response and neuronal apoptosis while enhancing axonal regeneration and improving motor function recovery. <em>In vitro,</em> PHI inhibited the release of inflammation-related factors from polarized BV2 cells in a dose-dependent manner. The online Swiss Target Prediction database predicted that toll-like receptor 4 (TLR4) was the target protein for PHI. In addition, Molecular Operating Environment software was used to perform molecular docking for PHI with the TLR4 protein; this resulted in a binding energy interaction of −6.7 kcal/mol. PHI inhibited microglia-mediated neuroinflammation, the production of reactive oxygen species (ROS), and activity of the NF-κb signaling pathway. PHI also increased mitochondrial membrane potential (MMP) in VSC 4.1 neuronal cells. In BV2 cells, PHI attenuated the overexpression of TLR4-induced microglial polarization and significantly suppressed the release of inflammatory cytokines.</p></div><div><h3>Conclusion</h3><p>PHI ameliorated SCI-induced neuroinflammation by modulating the TLR4/MYD88/NF-κB signaling pathway. PHI has the potential to be administered as a treatment for SCI and represents a novel candidate drug for addressing neuroinflammation mediated by microglial cells.</p></div><div><h3>The translational potential of this article</h3><p>We demonstrated that PHI is a potential drug candidate for the therapeutic management of SCI with promising developmental and translational applications.</p></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214031X24000858/pdfft?md5=9725131673a30662a4fc91b5d60a92a0&pid=1-s2.0-S2214031X24000858-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141930903","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":"Neural and immune roles in osteoarthritis pain: Mechanisms and intervention strategies","authors":"","doi":"10.1016/j.jot.2024.07.010","DOIUrl":"10.1016/j.jot.2024.07.010","url":null,"abstract":"<div><p>Pain is the leading symptom for most individuals with osteoarthritis (OA), a complex condition marked by joint discomfort. Recently, the dynamic interplay between the nervous and immune systems has become a focal point for understanding pain regulation. Despite this, there is still a substantial gap in our comprehensive understanding of the neuroimmune interactions and their effects on pain in OA. This review examines the bidirectional influences between immune cells and nerves in OA progression. It explores current approaches that target neuroimmune pathways, including promoting M2 macrophage polarization and specific neuronal receptor targeting, for effective pain reduction.</p></div><div><h3>Translational potential statement</h3><p>This review provides a comprehensive overview of the mechanisms underlying the interplay between the immune system and nervous system during the progression of OA, as well as their contributions to pain. Additionally, it compiles existing intervention strategies targeting neuroimmunity for the treatment of OA pain. This information offers valuable insights for researchers seeking to address the challenge of OA pain.</p></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214031X24000834/pdfft?md5=9519f147b0595becb63ec5dce52cd1fd&pid=1-s2.0-S2214031X24000834-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141930906","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":"Treatment effects, adverse outcomes and cardiovascular safety of romosozumab – Existing worldwide data: A systematic review and meta-analysis","authors":"","doi":"10.1016/j.jot.2024.07.011","DOIUrl":"10.1016/j.jot.2024.07.011","url":null,"abstract":"<div><h3>Background</h3><p>Romosozumab is a novel monoclonal antibody that binds to sclerostin, and has dual effects of increasing bone formation and decreasing bone resorption, giving it a unique mechanism of action. The objective of this study was to perform a systematic review and meta-analysis based on existing worldwide data on treatment effects and safety of romosozumab in randomized controlled trials.</p></div><div><h3>Methods</h3><p>A systematic search was carried out on four databases including PubMed, Embase, Web of Science and Cochrane Central Register of Controlled Trials (CENTRAL). The keywords used for search was “(romosozumab) AND (osteoporosis OR safety)”. Randomized controlled trial or post-hoc studies of the included randomized controlled trial which studied the effects and safety of romosozumab were included. The quality of selected studies was assessed with the Cochrane collaboration tool and the PEDro scale.</p></div><div><h3>Results</h3><p>20 studies were included for qualitative analysis. 14 studies were included for meta-analysis. In total, there were 13,507 (n = 13,507) participants with 637 men and 12,870 women from original cohorts. The overall mean difference was in favor of romosozumab treatment for lumbar spine (10.04 (95 % confidence interval (CI) = 7.51–12.57; p &lt; 0.00001)), total hip (4.04 (95 % CI = 3.10–4.99; p &lt; 0.00001)) and femoral neck bone mineral density (3.77 (95 % CI = 2.90–4.64; p &lt; 0.00001)) at 12 months. There was significantly less likelihood of new vertebral fractures with romosozumab compared to control (odds ratio (OR) 0.42 (95 % CI = 0.20–0.89); p = 0.02) at 12 months of treatment. There was significantly less likelihood of new vertebral fracture at 24 months with 12 months of romosozumab followed by sequential treatment with anti-resorptive compared to control with only anti-resorptive agent use (OR 0.36 (95 % CI = 0.18–0.71); p = 0.003). There was no significant difference in serious adverse events and fatal adverse events with use of romosozumab compared with control in our meta-analyses. There were no significant differences in serious cardiovascular events in Asian population of romosozumab with control group with 12 months of romosozumab treatment followed by 24 months of anti-resorptive agent with OR 1.09 (95 % CI = 0.40–2.96; P = 0.86). There was no significant difference between romosozumab group and control group for the median time to radiographic healing. Our qualitative analysis on Quantitative Computed Tomography (QCT), Finite element analysis (FEA) and bone biopsy analyses demonstrated that romosozumab improved parameters and measures in these domains as well.</p></div><div><h3>Conclusion</h3><p>In conclusion, our study showed that romosozumab was an effective agent to treat osteoporosis with high quality evidence. There were no significant differences in the adverse events, serious adverse events, fatal adverse events identified. Further subgroup analysis of cardiovascula","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214031X24000846/pdfft?md5=c082cecae230e71276e7e24236e393f5&pid=1-s2.0-S2214031X24000846-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141930905","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":"Exosomes derived from bone marrow mesenchymal stem cell preconditioned by low-intensity pulsed ultrasound stimulation promote bone–tendon interface fibrocartilage regeneration and ameliorate rotator cuff fatty infiltration","authors":"","doi":"10.1016/j.jot.2024.07.009","DOIUrl":"10.1016/j.jot.2024.07.009","url":null,"abstract":"<div><h3>Background</h3><p>Fibrovascular scar healing of bone-tendon interface (BTI) instead of functional fibrocartilage regeneration is the main concern associated with unsatisfactory prognosis in rotator cuff repair. Mesenchymal stem cells (MSCs) exosomes have been reported to be a new promising cell-free approach for rotator cuff healing. Whereas, controversies abound in whether exosomes of native MSCs alone can effectively induce chondrogenesis.</p></div><div><h3>Purpose</h3><p>To explore the effect of exosomes derived from low-intensity pulsed ultrasound stimulation (LIPUS)-preconditioned bone marrow mesenchymal stem cells (LIPUS-BMSC-Exos) or un-preconditioned BMSCs (BMSC-Exos) on rotator cuff healing and the underlying mechanism.</p></div><div><h3>Methods</h3><p>C57BL/6 mice underwent unilateral supraspinatus tendon detachment and repair were randomly assigned to saline, BMSCs-Exos or LIPUS-BMSC-Exos injection therapy. Histological, immunofluorescent and biomechanical tests were detected to investigate the effect of exosomes injection on BTI healing and muscle fatty infiltration of the repaired rotator cuff. <em>In vitro</em>, native BMSCs were incubated with BMSC-Exos or LIPUS-BMSC-Exos and then chondrogenic/adipogenic differentiation were observed. Further, quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the chondrogenesis/adipogenesis-related miRNA profiles of LIPUS-BMSC-Exos and BMSC-Exos. The chondrogenic/adipogenic potential of the key miRNA was verified through function recover test with its mimic and inhibitor.</p></div><div><h3>Results</h3><p>The results indicated that the biomechanical properties of the supraspinatus tendon-humeral junction were significantly improved in the LIPUS-BMSC-Exos group than that of the BMSCs-Exos group. The LIPUS-BMSC-Exos group also exhibited a higher histological score and more newly regenerated fibrocartilage at the repair site at postoperative 2 and 4 weeks and less fatty infiltration at 4 weeks than the BMSCs-Exos group. <em>In vitro</em>, co-culture of BMSCs with LIPUS-BMSC-Exos could significantly promote BMSCs chondrogenic differentiation and inhibit adipogenic differentiation. Subsequently, qRT-PCR revealed significantly higher enrichment of chondrogenic miRNAs and less enrichment of adipogenic miRNAs in LIPUS-BMSC-Exos compared with BMSC-Exos. Moreover, we demonstrated that this chondrogenesis-inducing potential was primarily attributed to miR-140, one of the most abundant miRNAs in LIPUS-BMSC-Exos.</p></div><div><h3>Conclusion</h3><p>LIPUS-preconditioned BMSC-Exos can effectively promote BTI fibrocartilage regeneration and ameliorate supraspinatus fatty infiltration by positive regulation of pro-chondrogenesis and anti-adipogenesis, which was primarily through delivering miR-140.</p></div><div><h3>The translational potential of this article</h3><p>These findings propose an innovative “LIPUS combined Exosomes strategy” for rotator cuff healing which combine","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214031X24000822/pdfft?md5=14328dea7fe6bbbfb76ea8736ec53f5c&pid=1-s2.0-S2214031X24000822-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141886382","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":"Structure, ingredient, and function-based biomimetic scaffolds for accelerated healing of tendon-bone interface","authors":"","doi":"10.1016/j.jot.2024.07.007","DOIUrl":"10.1016/j.jot.2024.07.007","url":null,"abstract":"<div><h3>Background</h3><p>Tendon-bone interface (TBI) repair is slow and challenging owing to its hierarchical structure, gradient composition, and complex function. In this work, enlightened by the natural characteristics of TBI microstructure and the demands of TBI regeneration, a structure, composition, and function-based scaffold was fabricated. <em>Methods</em>: The biomimetic scaffold was designed based on the “tissue-inducing biomaterials” theory: (1) a porous scaffold was created with poly-lactic-co-glycolic-acid, nano-hydroxyapatite and loaded with BMP2-gelatin_mp to simulate the bone (BP); (2) a hydrogel was produced from sodium alginate, type I collagen, and loaded with TGF-β3 to simulate the cartilage (CP); (3) the L-poly-lactic-acid fibers were oriented to simulate the tendon (TP). The morphology of tri-layered constructs, gelation kinetics, degradation rate, release kinetics and mechanical strength of the scaffold were characterized. Then, bone marrow mesenchymal stem cells (MSCs) and tenocytes (TT-D6) were cultured on the scaffold to evaluate its gradient differentiation inductivity. A rat Achilles tendon defect model was established, and BMSCs seeded on scaffolds were implanted into the lesionsite. The tendon-bone lesionsite of calcaneus at 4w and 8w post-operation were obtained for gross observation, radiological evaluation, biomechanical and histological assessment.</p></div><div><h3>Results</h3><p>The hierarchical microstructures not only endowed the scaffold with gradual composition and mechanical properties for matching the regional biophysical characteristics of TBI but also exhibited gradient differentiation inductivity through providing regional microenvironment for cells. Moreover, the scaffold seeded with cells could effectively accelerate healing in rat Achilles tendon defects, attributable to its enhanced differentiation performance.</p></div><div><h3>Conclusion</h3><p>The hierarchical scaffolds simulating the structural, compositional, and cellular heterogeneity of natural TBI tissue performed therapeutic effects on promoting regeneration of TBI and enhancing the healing quality of Achilles tendon.</p></div><div><h3>The translational potential of this article</h3><p>The novel scaffold showed the great efficacy on tendon to bone healing by offering a structural and compositional microenvironment. The results meant that the hierarchical scaffold with BMSCs may have a great potential for clinical application.</p></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214031X24000755/pdfft?md5=1a7b38fe7cfe7457456fbd09447bdeaf&pid=1-s2.0-S2214031X24000755-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141886383","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":"Mesenchymal stem cell–derived extracellular vesicles in joint diseases: Therapeutic effects and underlying mechanisms","authors":"","doi":"10.1016/j.jot.2024.07.005","DOIUrl":"10.1016/j.jot.2024.07.005","url":null,"abstract":"<div><p>Joint diseases greatly impact the daily lives and occupational functioning of patients globally. However, conventional treatments for joint diseases have several limitations, such as unsatisfatory efficacy and side effects, necessitating the exploration of more efficacious therapeutic strategies. Mesenchymal stem cell (MSC)-derived EVs (MSC-EVs) have demonstrated high therapeutic efficacyin tissue repair and regeneration, with low immunogenicity and tumorigenicity. Recent studies have reported that EVs-based therapy has considerable therapeutic effects against joint diseases, including osteoarthritis, tendon and ligament injuries, femoral head osteonecrosis, and rheumatoid arthritis. Herein, we review the therapeutic potential of various types of MSC-EVs in the aforementioned joint diseases, summarise the mechanisms underlying specific biological effects of MSC-EVs, and discuss future prospects for basic research on MSC-EV-based therapeutic modalities and their clinical translation. In general, this review provides an in-depth understanding of the therapeutic effects of MSC-EVs in joint diseases, as well as the underlying mechanisms, which may be beneficial to the clinical translation of MSC-EV-based treatment.</p><p>The translational potential of this article: MSC-EV-based cell-free therapy can effectively promote regeneration and tissue repair. When used to treat joint diseases, MSC-EVs have demonstrated desirable therapeutic effects in preclinical research. This review may supplement further research on MSC-EV-based treatment of joint diseases and its clinical translation.</p></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214031X24000731/pdfft?md5=97c1428bd4a1be09b08809c15972de16&pid=1-s2.0-S2214031X24000731-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141886381","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":"Mechanical loading on osteocytes regulates thermogenesis homeostasis of brown adipose tissue by influencing osteocyte-derived exosomes","authors":"","doi":"10.1016/j.jot.2024.06.012","DOIUrl":"10.1016/j.jot.2024.06.012","url":null,"abstract":"<div><h3>Background</h3><p>Osteocytes are the main stress-sensing cells in bone. The substances secreted by osteocytes under mechanical loading play a crucial role in maintaining body homeostasis. Osteocytes have recently been found to release exosomes into the circulation, but whether they are affected by mechanical loading or participate in the regulation of systemic homeostasis remains unclear.</p></div><div><h3>Methods</h3><p>We used a tail-suspension model to achieve mechanical unloading on osteocytes. Osteocyte-specific CD63 reporter mice were used for osteocyte exosome tracing. Exosome detection and inhibitor treatment were performed to confirm the effect of mechanical loading on exosome secretion by osteocytes. Co-culture, GW4869 and exosome treatment were used to investigate the biological functions of osteocyte-derived exosomes on brown adipose tissue (BAT) and primary brown adipocytes. Osteocyte-specific Dicer KO mice were used to screen for loading-sensitive miRNAs. Dual luciferase assay was performed to validate the selected target gene.</p></div><div><h3>Results</h3><p>Firstly, we found the thermogenic activity was increased in BAT of mice subjected to tail suspension, which is due to the effect of unloaded bone on circulating exosomes. Further, we showed that the secretion of exosomes from osteocytes is regulated by mechanical loading, and osteocyte-derived exosomes can reach BAT and affect thermogenic activity. More importantly, we confirmed the effect of osteocyte exosomes on BAT both in vivo and in vitro. Finally, we discovered that let-7e-5p contained in exosomes is under regulation of mechanical loading and regulates thermogenic activity of BAT by targeting <em>Ppargc1a</em>.</p></div><div><h3>Conclusion</h3><p>Exosomes derived from osteocytes are loading-sensitive, and play a vital role in regulation on BAT, suggesting that regulation of exosomes secretion can restore homeostasis.</p></div><div><h3>The translational potential of this article</h3><p>This study provides a biological rationale for using osteocyte exosomes as potential agents to modulate BAT and even whole-body homeostasis. It also provides a new pathological basis and a new treatment approach for mechanical unloading conditions such as spaceflight.</p></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11287067/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141860123","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":"Does concomitant meniscus repair and meniscectomy show different efficacy in anterior cruciate ligament reconstruction? A systematic review and meta-analysis","authors":"","doi":"10.1016/j.jot.2024.07.004","DOIUrl":"10.1016/j.jot.2024.07.004","url":null,"abstract":"<div><h3>Aims</h3><p>Currently, it is advised to perform meniscal repair instead of meniscectomy in certain cases of primary anterior cruciate ligament reconstruction (ACLR). However, the level of evidence is low. Therefore, this study aimed to compare the effectiveness of meniscectomy and meniscus repair in addition to ACLR.</p></div><div><h3>Methods</h3><p>The systematic search was conducted in three online databases (EMBASE, MEDLINE, and Cochrane) from inception until October 2021 for the literature on primary ACLR and concomitant meniscal surgery. Eligible studies compared the following outcomes between meniscal repair and meniscectomy groups: the Knee injury and Osteoarthritis Outcome Score (KOOS), Lysholm score, International Knee Documentation Committee (IKDC) score, and KT-arthrometer examinations. Lastly, we calculated pooled mean differences (MDs) with 95 % confidence intervals (CIs) from the change between pre- and post-intervention values.</p></div><div><h3>Results</h3><p>Of 10,565 studies, 22 met the inclusion criteria, with a follow-up between 6 and 43 months. We found no difference when comparing the KOOS subscale changes—only in the KOOS pain subscale (MD = −1.6; CI: −2.48, −0.72). However, these results were not clinically significant. We analyzed the lateral and media meniscal injuries separately and concluded the same results regarding KOOS changes. We found no significant differences in the Lysholm score change (MD = −2.61; CI: −5.51, 0.29), changes in IKDC score (MD = 1.08; CI: −4.05, 6.21) or the change for the KT-arthrometer side-to-side difference (MD = −0.50; CI: −1.06, 0.06).</p></div><div><h3>Conclusion</h3><p>Based on our result, we did not find a clinically significant difference between meniscus repair and meniscectomy during primary ACLR regarding patient-reported outcomes in a short-term follow-up.</p></div><div><h3>Translational potential</h3><p>Our research supports the prompt integration of findings into clinical practice for treating meniscus injuries during ACL reconstruction. We recommend considering both meniscus repair and meniscectomy, as the available data indicate their effectiveness. Further studies are necessary to assess the long-term impacts, particularly on osteoarthritis, and to identify patient subgroups that may benefit most from each technique.</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/S2214031X2400072X/pdfft?md5=03e714c69538490fbcec652ac8f984f3&pid=1-s2.0-S2214031X2400072X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141886384","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}