Journal of Orthopaedic Research®最新文献

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Tensor Fasciae Latae and Gluteus Maximus Muscles: Do They Contribute to Hip Abduction? 阔筋膜张肌和臀大肌:它们是否与髋外展有关?
IF 2.1 3区 医学
Journal of Orthopaedic Research® Pub Date : 2024-12-28 DOI: 10.1002/jor.26036
Armando Hoch, Dimitris Dimitriou, Jessica Wolf-Wettstein, Jan Rosner, Martin Schubert, Jose Aguirre, Urs Eichenberger, Patrick Zingg, Paul Borbas
{"title":"Tensor Fasciae Latae and Gluteus Maximus Muscles: Do They Contribute to Hip Abduction?","authors":"Armando Hoch,&nbsp;Dimitris Dimitriou,&nbsp;Jessica Wolf-Wettstein,&nbsp;Jan Rosner,&nbsp;Martin Schubert,&nbsp;Jose Aguirre,&nbsp;Urs Eichenberger,&nbsp;Patrick Zingg,&nbsp;Paul Borbas","doi":"10.1002/jor.26036","DOIUrl":"10.1002/jor.26036","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 <p>Hip abductors are essential for hip function. To understand abduction weakness, it is important to know which muscles contribute to abduction force. Our aim was to investigate the effects of an experimentally induced weakness of the different muscles (tensor fasciae latae [TFL], gluteus medius and minimus (Gmed/min), gluteus maximus [Gmax]) on the abduction force. Ten participants received sequential nerve blocks of the TFL, the Gmed/min, and the Gmax. Subsequently, abduction force was measured in the lateral decubitus position in three sagittal positions of the hip (30° flexion, neutral, 30° extension). In 30° flexion, the average abduction force was 220 N without block, 187 N with block of the TFL, 83 N with block of the Gmed/min, and 97 N with block of the Gmax, respectively. In neutral position, average abduction force was 213 N without block, 200 N with block of the TFL, 82 N with block of the Gmed/min, and 115 N with block of the Gmax, respectively. In 30° extension, average abduction force was 116 N without block, 146 N with block of TFL, 61 N with block of the Gmed/min, and 94 N with block of the Gmax, respectively. An induced weakness of the TFL reduces abduction force only in 30° of hip flexion by 15%. It is not highly relevant as an abductor. An induced weakness of the Gmax reduces abduction force in flexion by 43%−56%, depending on the position. It is, therefore, highly relevant as an abductor of the hip.</p>\u0000 </section>\u0000 </div>","PeriodicalId":16650,"journal":{"name":"Journal of Orthopaedic Research®","volume":"43 4","pages":"828-833"},"PeriodicalIF":2.1,"publicationDate":"2024-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142895509","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
Comparison of Marker-Based RSA and CT-RSA for Analyzing Micromotions After Distal Radius Osteotomy: A 1-Year Retrospective Study of 24 Patients 基于标记的RSA与CT-RSA在桡骨远端截骨术后微运动分析中的比较:24例患者1年回顾性研究。
IF 2.1 3区 医学
Journal of Orthopaedic Research® Pub Date : 2024-12-27 DOI: 10.1002/jor.26031
Vasileios Angelomenos, Olof Sandberg, Bita Shareghi, Michael Ullman
{"title":"Comparison of Marker-Based RSA and CT-RSA for Analyzing Micromotions After Distal Radius Osteotomy: A 1-Year Retrospective Study of 24 Patients","authors":"Vasileios Angelomenos,&nbsp;Olof Sandberg,&nbsp;Bita Shareghi,&nbsp;Michael Ullman","doi":"10.1002/jor.26031","DOIUrl":"10.1002/jor.26031","url":null,"abstract":"<p>Radiostereometric Analysis (RSA) is the most accurate method for determining early micromotions of orthopedic implants. Computed Tomography Radiostereometric Analysis (CT-RSA) is a method that can be used to determine implant and bone micromovements using low-dose CT scans. This study aimed to evaluate the reliability of the CT-RSA method in measuring the interfragmental mobility in patients who have undergone a correction osteotomy due to a malunited distal radius fracture. Twenty-four patients were included and operated with a radiolucent volar plate. Markers were embedded in the plate and bone. RSA and CT examinations were obtained postoperatively up to 1-year postoperative. Micromovements of the distal radius segment relative to the proximal were compared between the methods with paired analysis and Bland–Altman plots. The limits of clinical significance were: dorsal/volar tilt &lt; 10°, radial shortening &lt; 5 mm, radial inclination ≥ 15°, and radial shift &lt; 5 mm. For the dorsal/volar tilt, the paired analysis between the two methods, showed a mean difference (95% CI) of −0.06° (−0.67 to 0.55), for radial compression-0.04 mm (−0.09 to 0.01), for radial inclination 0.21° (−0.06 to 0.48), and for radial shift −0.07 mm (−0.21 to 0.07). The paired analysis for micromotions showed that the thresholds of clinical significance are excluded from the difference's 95% CI. The Bland–Altman plots showed comparable results up to 1 year, considering clinically relevant thresholds. In conclusion, the CT-RSA method is comparable to that of marker-based RSA in measuring micromotions after wrist osteotomy, as the differences between the methods are not clinically significant.</p>","PeriodicalId":16650,"journal":{"name":"Journal of Orthopaedic Research®","volume":"43 3","pages":"660-670"},"PeriodicalIF":2.1,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jor.26031","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142895487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Moderate- and High-Speed Treadmill Running Exercise Have Minimal Impact on Rat Achilles Tendon 中等和高速跑步机运动对大鼠跟腱的影响最小。
IF 2.1 3区 医学
Journal of Orthopaedic Research® Pub Date : 2024-12-27 DOI: 10.1002/jor.26030
Margaret K. Tamburro, Kelsey A. Bonilla, Snehal S. Shetye, Thomas P. Leahy, Jeremy D. Eekhoff, Min-Soo Kim, Christopher Petucci, John W. Tobias, Daniel C. Farber, Louis J. Soslowsky
{"title":"Moderate- and High-Speed Treadmill Running Exercise Have Minimal Impact on Rat Achilles Tendon","authors":"Margaret K. Tamburro,&nbsp;Kelsey A. Bonilla,&nbsp;Snehal S. Shetye,&nbsp;Thomas P. Leahy,&nbsp;Jeremy D. Eekhoff,&nbsp;Min-Soo Kim,&nbsp;Christopher Petucci,&nbsp;John W. Tobias,&nbsp;Daniel C. Farber,&nbsp;Louis J. Soslowsky","doi":"10.1002/jor.26030","DOIUrl":"10.1002/jor.26030","url":null,"abstract":"<p>Exercise influences clinical Achilles tendon health in humans, but animal models of exercise-related Achilles tendon changes are lacking. Moreover, previous investigations of the effects of treadmill running exercise on rat Achilles tendon demonstrate variable outcomes. Our objective was to assess the functional, structural, cellular, and biomechanical impacts of treadmill running exercise on rat Achilles tendon with sensitive in and ex vivo approaches. Three running levels were assessed over the course of 8 weeks: control (cage activity), moderate-speed (treadmill running at 10 m/min, no incline), and high-speed (treadmill running at 20 m/min, 10° incline). We hypothesized that moderate-speed treadmill running would beneficially impact tendon biomechanics through increased tenocyte cellularity, metabolism, and anabolism whereas high-speed treadmill running would cause a tendinopathic phenotype with compromised tendon biomechanics due to pathologic tenocyte differentiation, metabolism, and catabolism. Contrary to our hypothesis, treadmill running exercise at these speeds had a nominal effect on the rat Achilles tendon. Treadmill running modestly influenced tenocyte metabolism and nuclear aspect ratio as well as viscoelastic tendon properties but did not cause a tendinopathic phenotype. These findings highlight the need for improved models of exercise- and loading-related tendon changes that can be leveraged to develop strategies for tendinopathy prevention and treatment.</p>","PeriodicalId":16650,"journal":{"name":"Journal of Orthopaedic Research®","volume":"43 3","pages":"519-530"},"PeriodicalIF":2.1,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jor.26030","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142895493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A Micro-CT Based Cadaveric Study Investigating Bone Density Changes During Hip Arthroplasty Surgery 一项基于显微ct的尸体研究探讨了髋关节置换术中骨密度的变化。
IF 2.1 3区 医学
Journal of Orthopaedic Research® Pub Date : 2024-12-26 DOI: 10.1002/jor.26032
Vineet Seemala, Mark A. Williams, Richard King, Sofia Goia, Paul F. Wilson, Arnab Palit
{"title":"A Micro-CT Based Cadaveric Study Investigating Bone Density Changes During Hip Arthroplasty Surgery","authors":"Vineet Seemala,&nbsp;Mark A. Williams,&nbsp;Richard King,&nbsp;Sofia Goia,&nbsp;Paul F. Wilson,&nbsp;Arnab Palit","doi":"10.1002/jor.26032","DOIUrl":"10.1002/jor.26032","url":null,"abstract":"<p>The impact of broaching and uncemented implantation on bone density during total hip arthroplasty (THA) remains unclear. Previous studies have typically examined extracted bone sections, which may not directly correlate with outcomes in human hip systems. This study aimed to evaluate bone density changes resulting from broaching and uncemented implantation using micro-computed tomography (μCT) on cadaveric samples. An in-house density calibration phantom (DCP) was developed by validating the densities of polymer inserts through mass and volume measurements. Its performance was then evaluated using lamb bone in comparison with a commercial DCP (QRM-50124). The sensitivity of density predictions to μCT scan parameters was also evaluated with the lamb bone. Additionally, density predictions from medical-CT and μCT scans were compared using the in-house DCP. Finally, uncemented THA procedures were performed on three cadaveric femurs, each undergoing three μCT scans at various surgical stages to assess changes in bone density. The density predictions obtained using the in-house DCP achieved an accuracy of ±0.097 g/cc compared to QRM-50124, with a precision of ±0.052 g/cc. The sensitivity to changes in μCT scan parameters was ±0.022 g/cc. Notably, density predictions from medical-CT and μCT scans were similar, particularly in cortical bone. Broaching and implantation led to an average increase in bone density of 0.137 g/cc, which was attributed to the accumulation of bone debris around the bone-implant interface. This accumulation raised the bone volume fraction, ranging from 3.31% to 20.69%, which acts as an autograft. These measurements have been made for the first time using a µCT and an in-house DCP.</p>","PeriodicalId":16650,"journal":{"name":"Journal of Orthopaedic Research®","volume":"43 4","pages":"818-827"},"PeriodicalIF":2.1,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jor.26032","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142895482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Evaluation of Glenohumeral Joint Kinematics Following the Latarjet and Eden-Hybinette Procedures a Dynamic Radiostereometric Cadaver Study Latarjet和Eden-Hybinette手术后肩关节运动学的评估——一项动态放射体测尸体研究。
IF 2.1 3区 医学
Journal of Orthopaedic Research® Pub Date : 2024-12-24 DOI: 10.1002/jor.26028
Josephine Olsen Kipp, Theis Muncholm Thillemann, Emil Toft Petersen, Sepp de Raedt, Lærke Borgen, Annemarie Brüel, Thomas Falstie-Jensen, Maiken Stilling
{"title":"Evaluation of Glenohumeral Joint Kinematics Following the Latarjet and Eden-Hybinette Procedures a Dynamic Radiostereometric Cadaver Study","authors":"Josephine Olsen Kipp,&nbsp;Theis Muncholm Thillemann,&nbsp;Emil Toft Petersen,&nbsp;Sepp de Raedt,&nbsp;Lærke Borgen,&nbsp;Annemarie Brüel,&nbsp;Thomas Falstie-Jensen,&nbsp;Maiken Stilling","doi":"10.1002/jor.26028","DOIUrl":"10.1002/jor.26028","url":null,"abstract":"<div>\u0000 \u0000 <p>Anterior shoulder instability with glenoid bone lesion can be treated with the Eden-Hybinette procedure utilizing a tricortical iliac crest bone graft or the Latarjet procedure. This study aimed to evaluate the glenohumeral joint (GHJ) kinematics throughout an external shoulder rotation following the Eden-Hybinette and Latarjet procedures. Nine human specimens were examined with dynamic radiostereometry during a GHJ external rotation with anteriorly directed loads from 0 to 30 N. In 30- and 60-degree GHJ abduction, the kinematics (measured as the humeral head center and contact point) was sequentially recorded for a 15% anterior glenoid bone lesion, the Eden-Hybinette, and the Latarjet procedure. The Latarjet and Eden-Hybinette procedures resulted in up to 9.7 mm (95%CI 0.5; 18.8) more posterior and a 7.4 mm (95%CI 0.3; 14.4) superior humeral head center location compared to the glenoid bone lesion. With 0–20 N anterior directed loads, the Latarjet procedure resulted in a more posterior humeral head center and contact point of up to 7.6 mm (95%CI 3.6; 11.5), especially in 60 degrees of GHJ abduction, compared to the Eden-Hybinette procedure. Opposite, at 30 N anterior-directed load, the Eden-Hybinette procedure resulted in a more posterior humeral head center of up to 7.6 mm (95%CI 0.3; 14.9) in 30 degrees GHJ abduction compared to the Latarjet procedure. The results support considering the Latarjet procedures in patients who need the stabilizing effect with the arm in the abducted and externally rotated position (e.g., throwers) and the Eden-Hybinette procedure in patients exposed to high anterior-directed loads with the arm at lower abduction angles (e.g., epilepsia).</p>\u0000 </div>","PeriodicalId":16650,"journal":{"name":"Journal of Orthopaedic Research®","volume":"43 3","pages":"492-504"},"PeriodicalIF":2.1,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882190","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
Synovial fluid dual-biomarker algorithm accurately differentiates osteoarthritis from inflammatory arthritis 滑液双生物标志物算法可准确区分骨关节炎和炎性关节炎。
IF 2.1 3区 医学
Journal of Orthopaedic Research® Pub Date : 2024-12-18 DOI: 10.1002/jor.26005
Daniel Keter, Van Thai-Paquette, John Miamidian, Simmi Gulati, Krista Toler
{"title":"Synovial fluid dual-biomarker algorithm accurately differentiates osteoarthritis from inflammatory arthritis","authors":"Daniel Keter,&nbsp;Van Thai-Paquette,&nbsp;John Miamidian,&nbsp;Simmi Gulati,&nbsp;Krista Toler","doi":"10.1002/jor.26005","DOIUrl":"10.1002/jor.26005","url":null,"abstract":"<p>Osteoarthritis (OA) prevalence increases as the population ages. Diagnosing osteoarthritis often occurs in the late stages when cartilage degradation is severe, making it difficult to distinguish from other types of arthritis. Accurate differentiation of primary osteoarthritis from other arthritic conditions is crucial for effective treatment planning. A new diagnostic test has been developed that uses a dual-biomarker algorithm to inform osteoarthritis diagnosis. Synovial fluid from patients with confirmed primary osteoarthritis showed elevated levels of cartilage oligomeric matrix protein. However, this biomarker alone could not distinguish primary osteoarthritis from other inflammatory conditions that also cause cartilage deterioration. Therefore, a combinatorial algorithm using cartilage oligomeric matrix protein and Interleukin-8 concentrations was developed to differentiate primary osteoarthritis from inflammatory arthritis. Clinical decision limits for cartilage oligomeric matrix protein concentration and the cartilage oligomeric matrix protein to Interleukin-8 ratio were established and validated using 171 human knee synovial fluid specimens. The osteoarthritis algorithm demonstrated clinical sensitivity and specificity of 87.0% and 88.9%, respectively. This is the first report of a biomarker test that can differentiate primary osteoarthritis from inflammatory arthritis with a high degree of accuracy.</p>","PeriodicalId":16650,"journal":{"name":"Journal of Orthopaedic Research®","volume":"43 2","pages":"304-310"},"PeriodicalIF":2.1,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jor.26005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142846816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Correction to “Optical Spectroscopic Determination of Human Meniscus Composition” 对“人体半月板成分的光谱学测定”的修正。
IF 2.1 3区 医学
Journal of Orthopaedic Research® Pub Date : 2024-12-11 DOI: 10.1002/jor.26027
{"title":"Correction to “Optical Spectroscopic Determination of Human Meniscus Composition”","authors":"","doi":"10.1002/jor.26027","DOIUrl":"10.1002/jor.26027","url":null,"abstract":"<p>J. Ala-Myllymäki, J. T. J. Honkanen, J. Töyräs, and I. O. Afara, “Optical Spectroscopic Determination of Human Meniscus Composition,” <i>Journal of Orthopaedic Research</i> 34 (2016): 270–278. https://doi.org/10.1002/jor.23025.</p><p>Second sentence starting in page 272, the text “The light source and fiber optic probe were placed approximately 10 mm above the sample surface.” was incorrect. This should have read: “The light source and fiber optic probe were placed approximately 10 and 2 cm, respectively, above the sample surface.”</p><p>We apologize for this error.</p>","PeriodicalId":16650,"journal":{"name":"Journal of Orthopaedic Research®","volume":"43 3","pages":"714"},"PeriodicalIF":2.1,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jor.26027","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Bilateral waveform analysis of gait biomechanics presurgery to 12 months following ACL reconstruction compared to controls 与对照组相比,前交叉韧带重建术后12个月双侧步态生物力学波形分析。
IF 2.1 3区 医学
Journal of Orthopaedic Research® Pub Date : 2024-12-04 DOI: 10.1002/jor.26001
Christin Büttner, Caroline Lisee, Elizabeth Bjornsen, Ashley Buck, Natália Favoreto, Alexander Creighton, Ganesh Kamath, Jeffrey Spang, Jason R. Franz, Troy Blackburn, Brian Pietrosimone
{"title":"Bilateral waveform analysis of gait biomechanics presurgery to 12 months following ACL reconstruction compared to controls","authors":"Christin Büttner,&nbsp;Caroline Lisee,&nbsp;Elizabeth Bjornsen,&nbsp;Ashley Buck,&nbsp;Natália Favoreto,&nbsp;Alexander Creighton,&nbsp;Ganesh Kamath,&nbsp;Jeffrey Spang,&nbsp;Jason R. Franz,&nbsp;Troy Blackburn,&nbsp;Brian Pietrosimone","doi":"10.1002/jor.26001","DOIUrl":"10.1002/jor.26001","url":null,"abstract":"<p>The purpose of this study was to compare gait biomechanics between limbs and to matched uninjured controls (i.e., sex, age, and body mass index) preoperatively and at 2, 4, 6, and 12 months following primary unilateral anterior cruciate ligament reconstruction (ACLR). Functional mixed effects models were used to identify differences in gait biomechanics throughout the stance phase between the a) ACLR limb and uninvolved limb, b) ACLR limb and controls, and c) uninvolved limb and controls. Compared with the uninvolved limb, the ACLR limb demonstrated lesser knee extension moment (KEM; within 8–37% range of stance) during early stance as well as lesser knee flexion moment (KFM; 45–84%) and greater knee flexion angle (KFA; 43–90%) during mid- to late stance at all timepoints. Compared with controls, the ACLR limb demonstrated lesser vertical ground reaction force (vGRF; 5–26%), lesser KEM (7–47%), and lesser knee adduction moment (KAM; 12–35%) during early stance as well as greater vGRF (39–63%) and greater KFA (34–95%) during mid- to late stance at all timepoints. Compared with controls, the uninvolved limb demonstrated lesser KFA (1–56%) and lesser KEM (12–54%) during early to mid-stance at all timepoints. While gait becomes more symmetrical over the first 12 months post-ACLR, the ACLR and uninvolved limbs both demonstrate persistent aberrant gait biomechanics compared to controls. Biomechanical waveforms throughout stance can be generally described as less dynamic following ACL injury and ACLR compared with uninjured controls.</p>","PeriodicalId":16650,"journal":{"name":"Journal of Orthopaedic Research®","volume":"43 2","pages":"322-336"},"PeriodicalIF":2.1,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jor.26001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142770037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Disease modifying osteoarthritis drug discovery using a temporal phenotypic reporter in 3D aggregates of primary human chondrocytes 在原发性人软骨细胞的三维聚集体中使用时间表型报告基因发现疾病修饰性骨关节炎药物。
IF 2.1 3区 医学
Journal of Orthopaedic Research® Pub Date : 2024-12-03 DOI: 10.1002/jor.26021
Maria A. Cruz, Scott Gronowicz, Makan Karimzadeh, Kari Martyniak, Ramapaada Medam, Thomas J. Kean
{"title":"Disease modifying osteoarthritis drug discovery using a temporal phenotypic reporter in 3D aggregates of primary human chondrocytes","authors":"Maria A. Cruz,&nbsp;Scott Gronowicz,&nbsp;Makan Karimzadeh,&nbsp;Kari Martyniak,&nbsp;Ramapaada Medam,&nbsp;Thomas J. Kean","doi":"10.1002/jor.26021","DOIUrl":"10.1002/jor.26021","url":null,"abstract":"<p>Our aim was to develop a novel approach to identify disease-modifying drugs for osteoarthritis (OA), focusing on stimulating type II collagen anabolism in chondrocytes. As ELISA or western blot are destructive, laborious and time consuming, primary human chondrocytes expressing <i>Gaussia</i> luciferase under the control of the type II collagen promoter were developed and used. We cultured them in 3D cartilage aggregates under physioxia, to temporally screen a natural product library over 3-weeks. Hit compounds were analyzed for their potential targets in silico, first by structure, then by RNA-Seq. Two hit compounds were then further analyzed using biochemical assays, dose-response curves, and histological analyses to confirm their effects on type II collagen expression and chondrogenesis. Aromoline shows promise as a potential disease modifying compound, demonstrating an increase in type II collagen expression within cartilage sourced from chondrocytes of three distinct donors. Aromoline is a bisbenzylisoquinoline alkaloid that has been studied for its antiproliferative, anti-inflammatory, and antimicrobial properties, and we are the first to explore its effects on chondrocytes and chondrogenesis. In silico analysis revealed the dopamine receptor D4 (DRD4) as a potential target, confirmed by type II collagen upregulation after aromoline treatment and with DRD4-specific agonist ABT-724. This novel approach combining in silico and in vitro methods provides a platform for drug discovery in a challenging and under-researched area. In conclusion, a novel drug (aromoline) and target receptor (DRD4) were identified as stimulating type II collagen, with the future goal of treating or preventing OA.</p>","PeriodicalId":16650,"journal":{"name":"Journal of Orthopaedic Research®","volume":"43 3","pages":"541-556"},"PeriodicalIF":2.1,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142770039","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 发行资料-封面
IF 2.1 3区 医学
Journal of Orthopaedic Research® Pub Date : 2024-12-03 DOI: 10.1002/jor.25879
{"title":"Issue Information - Cover","authors":"","doi":"10.1002/jor.25879","DOIUrl":"https://doi.org/10.1002/jor.25879","url":null,"abstract":"","PeriodicalId":16650,"journal":{"name":"Journal of Orthopaedic Research®","volume":"43 1","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jor.25879","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142764249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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