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, Van Thai-Paquette, John Miamidian, Simmi Gulati, Krista Toler","doi":"10.1002/jor.26005","DOIUrl":"https://doi.org/10.1002/jor.26005","url":null,"abstract":"<p><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":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Correction to \"Optical Spectroscopic Determination of Human Meniscus Composition\".","authors":"","doi":"10.1002/jor.26027","DOIUrl":"https://doi.org/10.1002/jor.26027","url":null,"abstract":"","PeriodicalId":16650,"journal":{"name":"Journal of Orthopaedic Research®","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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, Caroline Lisee, Elizabeth Bjornsen, Ashley Buck, Natália Favoreto, Alexander Creighton, Ganesh Kamath, Jeffrey Spang, Jason R Franz, Troy Blackburn, Brian Pietrosimone","doi":"10.1002/jor.26001","DOIUrl":"https://doi.org/10.1002/jor.26001","url":null,"abstract":"<p><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":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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, Scott Gronowicz, Makan Karimzadeh, Kari Martyniak, Ramapaada Medam, Thomas J Kean","doi":"10.1002/jor.26021","DOIUrl":"https://doi.org/10.1002/jor.26021","url":null,"abstract":"<p><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 Gaussia 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":" ","pages":""},"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}
{"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}
{"title":"Issue Information - Editorial Board and TOC","authors":"","doi":"10.1002/jor.25878","DOIUrl":"https://doi.org/10.1002/jor.25878","url":null,"abstract":"","PeriodicalId":16650,"journal":{"name":"Journal of Orthopaedic Research®","volume":"43 1","pages":"1-4"},"PeriodicalIF":2.1,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jor.25878","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142764250","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}
{"title":"Multitask learning for automatic detection of meniscal injury on 3D knee MRI.","authors":"Yufan Wang, Mengjie Ying, Yangyang Yang, Yankai Chen, Haoyuan Wang, Tsung-Yuan Tsai, Xudong Liu","doi":"10.1002/jor.26024","DOIUrl":"https://doi.org/10.1002/jor.26024","url":null,"abstract":"<p><p>Magnetic resonance imaging (MRI) of the knee is the recommended diagnostic method before invasive arthroscopy surgery. Nevertheless, interpreting knee MRI scans is a time-consuming process that is vulnerable to inaccuracies and inconsistencies. We proposed a multitask learning network MCSNet<sub>att</sub> which efficiently introduces segmentation prior features and enhances classification results through multiscale feature fusion and spatial attention modules. The MRI studies and subsequent arthroscopic diagnosis of 259 knees were collected retrospectively. Models were trained based on multitask loss with coronal and sagittal sequences and fused using logistic regression (LR). We visualized the network's interpretability by the gradient-weighted class activation mapping method. The LR model achieved higher area under the curve and mean average precision of medial and lateral menisci than models trained on a single sagittal or coronal sequence. Our multitask model MCSNet<sub>at</sub> outperformed the single-task model CNet and two clinicians in classification, with accuracy, precision, recall, F1-score of 0.980, 1.000, 0.952, 0.976 for medial and 0.920, 0.905, 0.905, 0.905 for the lateral, respectively. With the assistance of model results and visualized saliency maps, both clinicians showed improvement in their diagnostic performance. Compared to the baseline segmentation model, our model improved dice similarity coefficient and the 95% Hausdorff distance (HD<sub>95</sub>) of the lateral meniscus for 2.3% and 0.860 mm in coronal images and 4.4% and 2.253 mm in sagittal images. Our multitask learning network quickly generated accurate clinicopathological classification and segmentation of knee MRI, demonstrating its potential to assist doctors in a clinical setting.</p>","PeriodicalId":16650,"journal":{"name":"Journal of Orthopaedic Research®","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142769886","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}
Daniel B Hoffman, Albino G Schifino, Marion A Cooley, Roger X Zhong, Junwon Heo, Courtney M Morris, Matthew J Campbell, Gordon L Warren, Sarah M Greising, Jarrod A Call
{"title":"Low intensity, high frequency vibration training to improve musculoskeletal function in a mouse model of volumetric muscle loss.","authors":"Daniel B Hoffman, Albino G Schifino, Marion A Cooley, Roger X Zhong, Junwon Heo, Courtney M Morris, Matthew J Campbell, Gordon L Warren, Sarah M Greising, Jarrod A Call","doi":"10.1002/jor.26023","DOIUrl":"https://doi.org/10.1002/jor.26023","url":null,"abstract":"<p><p>This study's objective was to investigate the extent to which two different levels of low-intensity vibration training (0.6 g or 1.0 g) affected musculoskeletal structure and function after a volumetric muscle loss (VML) injury in male C57BL/6J mice. All mice received a unilateral VML injury to the posterior plantar flexors. Mice were randomized into a control group (no vibration; VML-noTX), or one of two experimental groups. The two experimental groups received vibration training for 15-min/day, 5-days/week for 8 weeks at either 0.6 g (VML-0.6 g) or 1.0 g (VML-1.0 g) beginning 3-days after induction of VML. Muscles were analyzed for contractile and metabolic adaptations. Tibial bone mechanical properties and geometric structure were assessed by a three-point bending test and microcomputed tomography (µCT). Body mass-normalized peak isometric-torque was 18% less in VML-0.6 g mice compared with VML-noTx mice (p = 0.030). There were no statistically significant differences of vibration intervention on contractile power or muscle oxygen consumption (p ≥ 0.191). Bone ultimate load, but not stiffness, was ~16% greater in tibias of VML-1.0 g mice compared with those from VML-noTx mice (p = 0.048). Cortical bone volume was ~12% greater in tibias of both vibration groups compared with VML-noTx mice (p = 0.003). Importantly, cross-section moment of inertia, the primary determinant of bone ultimate load, was 44% larger in tibias of VML-0.6 g mice compared with VML-noTx mice (p = 0.006). These changes indicate that following VML, bones are more responsive to the selected vibration training parameters than muscle. Vibration training represents a possible adjuvant intervention to address bone deficits following VML.</p>","PeriodicalId":16650,"journal":{"name":"Journal of Orthopaedic Research®","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142751137","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}
Robert Z Tashjian, Jared Zitnay, Nikolas H Kazmers, Shivakumar R Veerabhadraiah, Antonio C Zelada, Matthew Honeggar, Matthew C Smith, Peter N Chalmers, Heath B Henninger, Michael J Jurynec
{"title":"Tenascin C deletion impairs tendon healing and functional recovery after rotator cuff repair.","authors":"Robert Z Tashjian, Jared Zitnay, Nikolas H Kazmers, Shivakumar R Veerabhadraiah, Antonio C Zelada, Matthew Honeggar, Matthew C Smith, Peter N Chalmers, Heath B Henninger, Michael J Jurynec","doi":"10.1002/jor.26025","DOIUrl":"10.1002/jor.26025","url":null,"abstract":"<p><p>The biological factors that affect healing after rotator cuff repair (RCR) are not well understood. Genetic variants in the extracellular matrix protein Tenascin C (TNC) are associated with impaired tendon healing and it is expressed in rotator cuff tendon tissue after injury, suggesting it may have a role in the repair process. The purpose of the current study was to determine the role of TNC on tendon healing after RCR in a murine model. The supraspinatus tendon was transected and repaired on the left shoulder of wild-type (WT-RCR), Tenascin C null (Tnc<sup>-</sup>-RCR) and Tnc heterozygous (Tnc<sup>+/-</sup>-RCR) mice. Controls included the unoperated, contralateral shoulder of WT-RCR, Tnc<sup>-</sup>RCR, Tnc<sup>+/-</sup>-RCR mice and unoperated shoulders from age and genotype matched controls. We performed histologic, activity testing, bulk RNA-seq, and biomechanical analyses. At 8-weeks post-RCR, Tnc<sup>-</sup> and Tnc<sup>+/-</sup> mice had severe bone and tendon defects following RCR. Tnc<sup>-</sup>-RCR mice had reduced activity after RCR including reduced wheel rotations, wheel duration, and wheel episode average velocity compared with WT-RCR. Loss of Tnc following RCR altered gene expression in the shoulder, including upregulation of sex hormone and WNT pathways and a downregulation of inflammation and cell cycle pathways. Tnc<sup>-</sup> mice had similar biomechanical properties after repair as WT. Further research is required to evaluate tissue specific alterations of Tnc, the interactions of Tnc and sex hormone and inflammation pathways as well as possible adjuvants to improve enthesis healing in the setting of reduced TNC function.</p>","PeriodicalId":16650,"journal":{"name":"Journal of Orthopaedic Research®","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142729777","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}
Tatjana Pastor, Ivan Zderic, Frank J P Beeres, Nader Helmy, R Geoff Richards, Philipp Kriechling, Ludmil Drenchev, Hristo K Skulev, Boyko Gueorguiev, Torsten Pastor
{"title":"45° helical plates are a valid alternative to straight plates for treatment of proximal humeral shaft fractures.","authors":"Tatjana Pastor, Ivan Zderic, Frank J P Beeres, Nader Helmy, R Geoff Richards, Philipp Kriechling, Ludmil Drenchev, Hristo K Skulev, Boyko Gueorguiev, Torsten Pastor","doi":"10.1002/jor.26020","DOIUrl":"https://doi.org/10.1002/jor.26020","url":null,"abstract":"<p><p>Helical plates used for proximal humeral shaft fracture fixation avoid the radial nerve distally as compared to straight plates. To investigate in a human cadaveric model the biomechanical competence of straight lateral plates versus 45° helical plates used for fixation of proximal comminuted humeral shaft fractures, eight pairs of human cadaveric humeri were instrumented using either a long straight PHILOS plate (Group 1) or a 45° helical plate (Group 2) for treatment of an unstable proximal humeral shaft fracture. All specimens were tested under non-destructive quasi-static loading in axial compression, internal and external rotation, and bending in four directions. Subsequently, progressively increasing cyclic loading in internal rotation was applied until failure and interfragmentary movements were monitored by motion tracking. Axial displacement (mm) was 3.13 ± 0.31 in Group 1 and 2.60 ± 0.42 in Group 2, p = 0.015. Flexion/extension deformation (°) in Group 1 and Group 2 was 0.56 ± 0.42 and 0.43 ± 0.23, p = 0.551. Varus/valgus deformation (°) was 6.39 ± 0.44 in Group 1 and 5.13 ± 0.87 in Group 2, p = 0.012. Shear (mm) and torsional (°) displacement were 5.36 ± 0.76 and 17.75 ± 1.06 in Group 1, and 5.03 ± 0.46 and 16.79 ± 1.36 in Group 2, p ≥ 0.090. Cycles to catastrophic failure were 10000 ± 1401 in Group 1 and 9082 ± 1933 in Group 2, p = 0.708. From a biomechanical perspective, 45° helical plating is associated with lower axial and varus/valgus displacement under axial loading and demonstrates comparable resistance to failure versus straight plating. Therefore, 45° helical plates can be considered as a valid alternative to straight plates for treatment of proximal humeral shaft fractures.</p>","PeriodicalId":16650,"journal":{"name":"Journal of Orthopaedic Research®","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142716529","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}