Journal of Orthopaedic Research®最新文献_第3页

Kartogenin Enhances Chondrogenic Differentiation of iPSC Derived MSCs (iMSCs) and Improves Outcomes in an Osteochondral Defect Model in Male Rats. Kartogenin促进iPSC衍生的MSCs （iMSCs）的成软骨分化并改善雄性大鼠骨软骨缺损模型的结果。

IF 2.1 3区医学

Journal of Orthopaedic Research® Pub Date : 2025-01-12 DOI: 10.1002/jor.26040

Samir Chihab, Nazir M Khan, Tracy Eng, Thanh Doan, Jarred M Kaiser, Hicham Drissi

{"title":"Kartogenin Enhances Chondrogenic Differentiation of iPSC Derived MSCs (iMSCs) and Improves Outcomes in an Osteochondral Defect Model in Male Rats.","authors":"Samir Chihab, Nazir M Khan, Tracy Eng, Thanh Doan, Jarred M Kaiser, Hicham Drissi","doi":"10.1002/jor.26040","DOIUrl":"10.1002/jor.26040","url":null,"abstract":"Osteochondral defects (OCD) pose a significant clinical challenge due to the limited self-repair capacity of cartilage, leading to pain, joint dysfunction, and progression to osteoarthritis. Cellular implantations of adult mesenchymal stem cells (MSCs) enhanced with treatment of factors, such as small molecule Kartogenin (KGN) to promote chondrogenic differentiation, are promising but these cells often encounter hypertrophy during differentiation, compromising long-term stability. Induced pluripotent stem cell-derived MSCs (iMSCs) offer greater proliferative and differentiation capacity than MSCs and may provide a superior source of cells for cartilage repair. We hypothesized that treatment of iMSCs with TGFβ3 and KGN would enhance chondrogenic differentiation and that implanting these pellets into a rat OCD model would promote de novo cartilage regeneration and reduce pain behavior. We pellet cultured iMSCs derived from articular chondrocytes and treated with various conditions of TGFβ3 and KGN. We then assessed the in vivo performance of the pellets using a trochlear osteochondral defect in male Lewis rats. Co-treatment of iMSC pellets with TGFβ3 and KGN showed more pronounced chondrogenic differentiation than sequential treatment and exhibited stronger expression of chondrogenic genes. Implantation of the TGFβ3/KGN-treated iMSC pellets into OCD resulted in modest repair, as observed via gross morphology, effectively prevented the onset of joint hyperalgesia, and helped to maintain normal gait out to 12 weeks post-implantation compared to untreated OCD rats. Our study highlights the potential of KGN to enhance iMSC pellet chondrogenesis, offering a scaffold-free, cell-based therapy that could simplify clinical translation and improve outcomes for patients with cartilage injuries.","PeriodicalId":16650,"journal":{"name":"Journal of Orthopaedic Research®","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Muscle Contraction Is Essential for Tendon Healing and Muscle Function Recovery After Achilles Tendon Rupture and Surgical Repair. 在跟腱断裂和手术修复后，肌肉收缩是肌腱愈合和肌肉功能恢复的必要条件。

IF 2.1 3区医学

Journal of Orthopaedic Research® Pub Date : 2025-01-12 DOI: 10.1002/jor.26044

Moe Yoneno, Yuki Minegishi, Haruna Takahashi, Kei Takahata, Himari Miyamoto, Yuna Usami, Takanori Kokubun

{"title":"Muscle Contraction Is Essential for Tendon Healing and Muscle Function Recovery After Achilles Tendon Rupture and Surgical Repair.","authors":"Moe Yoneno, Yuki Minegishi, Haruna Takahashi, Kei Takahata, Himari Miyamoto, Yuna Usami, Takanori Kokubun","doi":"10.1002/jor.26044","DOIUrl":"https://doi.org/10.1002/jor.26044","url":null,"abstract":"Incomplete tendon healing and postponed muscle weakness after Achilles tendon rupture and surgical repair lead to poor performance in patient activities. Although the effectiveness of postoperative early functional rehabilitation has been proven, the priority and each effect of specific methods in early rehabilitation remain unclear. We hypothesized early muscle contraction exercises without joint motion would promote tendon healing and prevent calf muscle atrophy; in contrast, early static stretching after surgical repair would not contribute to tendon healing and induce calf muscle atrophy. C57Bl/6 mice underwent Achilles tendon rupture and suture repair, followed by different methods of post-surgery interventions: a non-exercise group, a Static stretching group, and an Electrical muscle stimulation group. 3 and 5 weeks after surgery, we assessed ex vivo tendon mechanical properties, collagen fiber alignment, and histological muscle properties. Electrical Muscle Stimulation restored the recovery of tendon mechanical properties and muscle strength more quickly than Static stretching. Static stretching had no additional effect on them compared to the non-exercise. Our results suggested that calf muscle contraction was essential as a post-surgery early functional rehabilitation to load tensile forces on tendons and improve Achilles tendon healing. Additionally, early muscle contractions naturally promote restoring muscle function after the rupture, but further research is needed to optimize muscle contraction protocols.","PeriodicalId":16650,"journal":{"name":"Journal of Orthopaedic Research®","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Development of a Mouse Model of Enthesis-Specific NF-κB Activation. 合成特异性NF-κB激活小鼠模型的建立。

IF 2.1 3区医学

Journal of Orthopaedic Research® Pub Date : 2025-01-09 DOI: 10.1002/jor.26035

McKenzie E Sup, Adam C Abraham, Min Kyu M Kim, Stavros Thomopoulos

{"title":"Development of a Mouse Model of Enthesis-Specific NF-κB Activation.","authors":"McKenzie E Sup, Adam C Abraham, Min Kyu M Kim, Stavros Thomopoulos","doi":"10.1002/jor.26035","DOIUrl":"https://doi.org/10.1002/jor.26035","url":null,"abstract":"Enthesitis, or inflammation specific to sites in the body where tendon inserts into bone, can arise in isolated joints from overuse or in multiple joints as a complication of an autoimmune condition such as psoriatic arthritis or spondyloarthritis. However, the pathogenesis of enthesitis is not well understood, so treatment strategies are limited. A clinically relevant animal model of enthesitis would allow investigators to determine mechanisms driving the disease and evaluate novel therapies. Therefore, we developed a murine model of inducible enthesis-specific inflammation by constitutively activating the NF-κB pathway in Gli1+ cells. Gli1CreERT mice were crossed with IKKβ-overexpression mice and given tamoxifen injections 5 days postnatally to induce enthesitis. Sixteen weeks of IKKβ overexpression in enthesis cells led to impaired mechanical properties, subtle histologic changes, and changes to expression of extracellular matrix- and inflammation-related genes. Increased loading from treadmill overuse activity did not exacerbate this phenotype. Clinical significance: The new murine model may have utility for studying the pathogenesis of enthesitis and approaches to treat the condition.","PeriodicalId":16650,"journal":{"name":"Journal of Orthopaedic Research®","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142950559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A Novel Isotropic Optical Fiber: Antimicrobial Effect of Blue Light on Drug Resistant Organisms. 一种新型各向同性光纤：蓝光对耐药生物的抗菌作用。

IF 2.1 3区医学

Journal of Orthopaedic Research® Pub Date : 2025-01-07 DOI: 10.1002/jor.26042

Megan H Goh, Robert A Rabiner, Joseph J Connolly, Santiago A Lozano-Calderon, Antonia F Chen

{"title":"A Novel Isotropic Optical Fiber: Antimicrobial Effect of Blue Light on Drug Resistant Organisms.","authors":"Megan H Goh, Robert A Rabiner, Joseph J Connolly, Santiago A Lozano-Calderon, Antonia F Chen","doi":"10.1002/jor.26042","DOIUrl":"https://doi.org/10.1002/jor.26042","url":null,"abstract":"Drug-resistant organisms (DROs) necessitate the development of new therapies. Antimicrobial blue light (ABL) is a promising option, utilizing photoexcitation of endogenous bacterial components to generate reactive oxygen species, leading to bacterial death. The aim of this study is to investigate the effects of a novel isotropic optical fiber under in-vitro conditions on multidrug-resistant gram-negative Pseudomonas aeruginosa (MDR-Pa) and methicillin-resistant Staphylococcus aureus (MRSA). Time-to-kill assays were conducted in tubes containing 10 mL of 0.9% NaCl solution with an inoculum of 1 × 10⁵ CFU/mL for MDR-Pa or MRSA. The experiments were repeated at least three times per strain. Experimental tubes had either one (low power, LP) or two (high power, HP) optical fibers delivering five ABL wavelengths (405, 415, 435, 450, and 475 nm) over 60 min. Control tubes lacked optical fibers. Samples were taken at 0, 10, 20, 30, and 60 min, streaked on agar, and incubated to determine CFU/mL. Bactericidal reduction was defined as a ≥ 99.9% (≥ 3 log10) reduction in CFU/mL. One-way ANOVA were conducted. The novel isotropic optical fiber was able to exhibit bactericidal effects for MDR-Pa only under HP-ABL with a log10CFU/mL ± SD difference of -3.71 ± 0.01 at 60 min (p = 0.03). Conversely, the optical fiber exhibited bactericidal effects on MRSA under both LP-ABL and HP-ABL with a log10CFU/mL±SD difference of -3.73 ± 0.08 at 60 min (p = 0.03) and -3.07 ± 0.28 at 20 min (p = 0.02), respectively. The isotropic optical fiber demonstrated bactericidal effects on MRSA and MDR-Pa in in-vitro studies and shows potential as a therapeutic option for DROs.","PeriodicalId":16650,"journal":{"name":"Journal of Orthopaedic Research®","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142950556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A Novel Disulfidptosis-Related Risk Signature for Prognostic Prediction in Patients With Ewing Sarcoma. 一种用于预测尤文氏肉瘤患者预后的新型双歧杆菌相关风险标志。

IF 2.1 3区医学

Journal of Orthopaedic Research® Pub Date : 2025-01-07 DOI: 10.1002/jor.26033

Chunqing Che, Delei Song, Peng Xue, Xuqing Yin

{"title":"A Novel Disulfidptosis-Related Risk Signature for Prognostic Prediction in Patients With Ewing Sarcoma.","authors":"Chunqing Che, Delei Song, Peng Xue, Xuqing Yin","doi":"10.1002/jor.26033","DOIUrl":"https://doi.org/10.1002/jor.26033","url":null,"abstract":"Ewing sarcoma (ES) is a malignant bone tumor prevalent among children and adolescents. Disulfidptosis represents a novel form of cell death; however, the mechanism of disulfidptosis in ES remains unclear. Our aim is to explore the disulfidptosis-related prognostic signature in ES. Utilizing transcriptomic and clinical data of ES, disulfidptosis-related hub genes (DRHGs) were identified by differential gene expression analysis and Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression analysis. A disulfidptosis-related risk score model (DRRS) was constructed based on these DRHGs. The performance of DRRS was assessed using survival analysis and receiver operating characteristic curve analysis. Immune cell infiltration in different risk subgroups and correlations between DRRS and antitumor reagents were also analyzed. In this study, we developed a disulfidptosis-related prognostic feature based on LRPPRC (leucine rich pentatricopeptide repeat containing), IQGAP1 (IQ motif containing GTPase activating protein 1), NDUFS1 (NADH:ubiquinone oxidoreductase core subunit S1), and TLN1 (talin 1), which may serve as a predictive and independent risk factor for ES. ES patients in the high-risk group exhibited a poorer prognosis, had a higher proportion of myeloid-derived suppressor cells (MDSCs) and M2 type of tumor-associated macrophages, and showed heightened sensitivity to some antitumor agents such as nilotinib and olaparib. This study is the first to construct a disulfidptosis-related prognostic signature that may predict the prognosis and immune response in ES patients, thereby providing a new reference for understanding the mechanisms of ES and guiding immunotherapy.","PeriodicalId":16650,"journal":{"name":"Journal of Orthopaedic Research®","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142950549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Issue Information - Cover

IF 2.1 3区医学

Journal of Orthopaedic Research® Pub Date : 2025-01-06 DOI: 10.1002/jor.25881

引用次数: 0

Issue Information - Editorial Board and TOC

IF 2.1 3区医学

Journal of Orthopaedic Research® Pub Date : 2025-01-06 DOI: 10.1002/jor.25880

引用次数: 0

Finite Element Model of Patient-Specific Flanged Acetabular Components Highlights Biomechanical Effects of Bone Density and Cortical Shell Thickness. 患者特有的法兰髋臼部件的有限元模型强调骨密度和皮质壳厚度的生物力学效应。

IF 2.1 3区医学

Journal of Orthopaedic Research® Pub Date : 2025-01-05 DOI: 10.1002/jor.26037

Haena-Young Lee, Friedrich Boettner, Jason L Blevins, Jose A Rodriguez, Joseph D Lipman, Fernando J Quevedo González, Mathias P Bostrom, Timothy M Wright, Peter K Sculco

{"title":"Finite Element Model of Patient-Specific Flanged Acetabular Components Highlights Biomechanical Effects of Bone Density and Cortical Shell Thickness.","authors":"Haena-Young Lee, Friedrich Boettner, Jason L Blevins, Jose A Rodriguez, Joseph D Lipman, Fernando J Quevedo González, Mathias P Bostrom, Timothy M Wright, Peter K Sculco","doi":"10.1002/jor.26037","DOIUrl":"https://doi.org/10.1002/jor.26037","url":null,"abstract":"Patient-specific flanged acetabular components are utilized to treat failed total hip arthroplasties with severe acetabular defects. We previously developed and published a finite element model that investigated the impact of hip joint center lateralization on construct biomechanics during gait conditions. This model consisted of a patient-specific implant designed to address a superior-medial defect created in a standard pelvic geometry. This study aims to utilize the same model and examine how cortical shell thickness and ischial cancellous bone density affect the strain distribution in the bone and bone-implant micromotion. Using published studies and bone density analyses of patients who had undergone total hip arthroplasties with flanged acetabular components, we established a thickness range for the cortical shell (1.5, 1, and 0.75 mm) and two levels of ischial cancellous bone density (100% and 25%). We compared the resulting bone strains against the fatigue strength of the bone (0.3% strain) as a criterion for local bone failure and the bone-implant micromotion against the threshold associated with bone ingrowth (20 µm). A thinner pelvic cortical shell and lower ischial cancellous bone density increased areas of bone at risk of failure, particularly at the ischial screws (from 6% to 38%), and decreased areas compatible with bone ingrowth. These findings agree with our clinical knowledge that compromised ischial bone and inadequate ischial fixation negatively impact the survivorship of flanged acetabular components. This series establishes our modeling approach of a computational model that can be utilized to guide implant design to best treat unique acetabular defects.","PeriodicalId":16650,"journal":{"name":"Journal of Orthopaedic Research®","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142931954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Electrophoretic Deposition of Gentamicin Into Titania Nanotubes Prevents Evidence of Infection in a Mouse Model of Periprosthetic Joint Infection 庆大霉素在钛纳米管中的电泳沉积阻止了假体周围关节感染小鼠模型的感染证据。

IF 2.1 3区医学

Journal of Orthopaedic Research® Pub Date : 2024-12-31 DOI: 10.1002/jor.26029

John L. Hamilton, Sofia Gianotti, Julia Fischer, Greta Della Fara, Amandine Impergre, Francesca De Vecchi, Mohammed AbuAlia, Alfons Fischer, Adrienn Markovics, Markus A. Wimmer

{"title":"Electrophoretic Deposition of Gentamicin Into Titania Nanotubes Prevents Evidence of Infection in a Mouse Model of Periprosthetic Joint Infection","authors":"John L. Hamilton, Sofia Gianotti, Julia Fischer, Greta Della Fara, Amandine Impergre, Francesca De Vecchi, Mohammed AbuAlia, Alfons Fischer, Adrienn Markovics, Markus A. Wimmer","doi":"10.1002/jor.26029","DOIUrl":"10.1002/jor.26029","url":null,"abstract":"<div>\u0000 \u0000 Periprosthetic joint infection (PJI) is a leading cause and major complication of joint replacement failure. As opposed to standard-of-care systemic antibiotic prophylaxis for PJI, we developed and tested titanium femoral intramedullary implants with titania nanotubes (TNTs) coated with the antibiotic gentamicin and slow-release agent chitosan through electrophoretic deposition (EPD) in a mouse model of PJI. We hypothesized that these implants would enable local gentamicin delivery to the implant surface and surgical site, effectively preventing bacterial colonization. In the mouse PJI model, C57BL/6 mice received implants with TNTs coated with chitosan (chitosan group; control group) or with TNTs coated with chitosan and gentamicin (chitosan + gentamicin group; experimental group). Following implant placement, the surgical site was inoculated with 1 × 103 CFUs of Xen36 bioluminescent Staphylococcus aureus. All the mice in the chitosan group and none in the chitosan + gentamicin group had evidence of infection based on CFU analysis and bioluminescence imaging through the 14-day assessment postsurgery. Correspondingly, scanning electron microscopy analysis at the implant surface demonstrated bacterial biofilm only in the chitosan group. Furthermore, periosteal reaction and peri-implant bone loss at the femur were significantly reduced in the chitosan + gentamicin group. The chitosan + gentamicin group had reduced pain behavior, improved weight-bearing, and increased weight compared to the chitosan-control group. This study provides preclinical evidence supporting the efficacy of implants with TNTs coated with chitosan and gentamicin through EPD for preventing bacterial colonization and biofilm formation in a mouse model of PJI.\u0000 </div>","PeriodicalId":16650,"journal":{"name":"Journal of Orthopaedic Research®","volume":"43 3","pages":"671-681"},"PeriodicalIF":2.1,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142915212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Msx1-Modified Rat Bone Marrow Mesenchymal Stem Cell Therapy for Rotator Cuff Repair: A Comprehensive Analysis of Tendon-Bone Healing and Cellular Mechanisms. 用于肩袖修复的 Msx1 改性大鼠骨髓间充质干细胞疗法：腱-骨愈合和细胞机制的综合分析。

IF 2.1 3区医学

Journal of Orthopaedic Research® Pub Date : 2024-12-31 DOI: 10.1002/jor.26039

Kang Liu, Xia-Wei Fu, Zi-Min Wang

{"title":"Msx1-Modified Rat Bone Marrow Mesenchymal Stem Cell Therapy for Rotator Cuff Repair: A Comprehensive Analysis of Tendon-Bone Healing and Cellular Mechanisms.","authors":"Kang Liu, Xia-Wei Fu, Zi-Min Wang","doi":"10.1002/jor.26039","DOIUrl":"https://doi.org/10.1002/jor.26039","url":null,"abstract":"This study investigates the therapeutic potential of Msx1-overexpressing bone marrow mesenchymal stem cells (BMSCs) in enhancing tendon-bone healing in rotator cuff injuries. BMSCs were genetically modified to overexpress Msx1 and were evaluated in vitro for their proliferation, migration, and differentiation potential. Results demonstrated that Msx1 overexpression significantly increased BMSC proliferation and migration while inhibiting osteogenic and chondrogenic differentiation. In a rat model of acute rotator cuff injury, Msx1-BMSCs embedded in a hydrogel scaffold were implanted at the tendon-bone junction. Micro-CT analysis revealed substantial new bone formation in the Msx1-BMSC group, and histological evaluation showed organized collagen and cartilage structures at the repair site. Biomechanical testing further confirmed enhanced structural strength in the Msx1-BMSC-treated group. These findings suggest that Msx1 modification enhances BMSC-mediated repair by promoting cell proliferation and migration, facilitating tendon-bone integration. This Msx1-based approach presents a promising strategy for advancing regenerative therapies for rotator cuff injuries.","PeriodicalId":16650,"journal":{"name":"Journal of Orthopaedic Research®","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142909859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0