Rachel Gagliardi, Drew W Koch, Richard Loeser, Lauren V Schnabel
{"title":"Matrikine stimulation of equine synovial fibroblasts and chondrocytes results in an in vitro osteoarthritis phenotype.","authors":"Rachel Gagliardi, Drew W Koch, Richard Loeser, Lauren V Schnabel","doi":"10.1002/jor.26004","DOIUrl":"https://doi.org/10.1002/jor.26004","url":null,"abstract":"<p><p>Osteoarthritis (OA) is a debilitating disease that impacts millions of individuals and has limited therapeutic options. A significant hindrance to therapeutic discovery is the lack of in vitro OA models that translate reliably to in vivo preclinical animal models. An alternative to traditional inflammatory cytokine models is the matrikine stimulation model, in which fragments of matrix proteins naturally found in OA tissues and synovial fluid, are used to stimulate cells of the joint. The objective of this study was to determine if matrikine stimulation of equine synovial fibroblasts and chondrocytes with fibronectin fragments (FN7-10) would result in an OA phenotype. We hypothesized that FN7-10 stimulation of equine articular cells would result in an OA phenotype with gene and protein expression changes similar to those previously described for human chondrocytes stimulated with FN7-10. Synovial fibroblasts and chondrocytes isolated from four horses were stimulated in monolayer culture for 6 or 18 h with 1 µM purified recombinant 42 kD FN7-10 in serum-free media. At the conclusion of stimulation, RNA was collected for targeted gene expression analysis and media for targeted protein production analysis. Consistent with our hypothesis, FN7-10 stimulation resulted in significant alterations to many important genes that are involved in OA pathogenesis including increased expression of IL-1β, IL-4, IL-6, CCL2/MCP-1, CCL5/RANTES, CXCL6/GCP-2, MMP-1, MMP-3, and MMP13. The results of this study suggest that the equine matrikine stimulation model of OA may prove useful for in vitro experiments leading up to preclinical trials.</p>","PeriodicalId":16650,"journal":{"name":"Journal of Orthopaedic Research®","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142563501","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":"Timing of cartilage articulation following impact injury affects the response of surface zone chondrocytes.","authors":"Caroline L Thompson, Lawrence J Bonassar","doi":"10.1002/jor.26002","DOIUrl":"https://doi.org/10.1002/jor.26002","url":null,"abstract":"<p><p>Post-traumatic osteoarthritis develops following an inciting injury to a joint and results in cartilage degeneration. Mechanical loading, including articulation, drives anabolic responses in cartilage clinically, in vivo, and in vitro. Tribological articulation, or sliding of cartilage on a glass counterface, has long been used as an in vitro tool to study cartilage tissue behavior. However, it is unclear if tribological articulation affects chondrocyte fate following injury, and if the timing of articulation impacts the resultant effect. The goal of this study was to investigate the effect of tribological articulation on injured cartilage tissue at two time points: (i) performed immediately after injury and (ii) 24 h after injury. Neonatal bovine femoral cartilage explants were injured using a rapid spring-loaded impactor and subsequently subjected to tribological articulation. Cell death due to impact injury was highest near the articular surface, suggesting a strain-dependent mechanism. Immediate articulation following injury mitigated cell death compared to injury alone or delayed articulation; markers for both general cell death and early-stage apoptosis were markedly decreased in the explants that were immediately slid. Interestingly, mitigation of cell death due to sliding was most predominant at the cartilage surface. Tribological articulation is known to create fluid flow within the tissue, predominantly at the articular surface, which could drive the protective response seen here. Altogether, this work shows that perturbations to the cellular environment immediately following cartilage injury significantly impact chondrocyte fate.</p>","PeriodicalId":16650,"journal":{"name":"Journal of Orthopaedic Research®","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142558008","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}
Andreas Geisbüsch, Carina Gramer, Thomas Dreher, Niclas Hagen, Sébastien Hagmann, Tobias Renkawitz, Marco Götze
{"title":"Electromagnetic bone segment tracking in multiplanar osteotomies: A saw bone study.","authors":"Andreas Geisbüsch, Carina Gramer, Thomas Dreher, Niclas Hagen, Sébastien Hagmann, Tobias Renkawitz, Marco Götze","doi":"10.1002/jor.26000","DOIUrl":"https://doi.org/10.1002/jor.26000","url":null,"abstract":"<p><p>Computer assisted orthopedic surgery is used to improve precision. Electro-magnetic tracking has been shown to improve precision in mono-planar derotational osteotomies. However, studies are lacking to investigate its use in multiplanar osteotomies. For this purpose, 60 complex (derotation and extension) osteotomies were performed in standardized sawbones. Correction amount was randomly planned before the procedures. In 30 bones, the amount of correction was determined intraoperatively using conventional goniometric measurement while in the other 30 bones electro-magnetic tracking was used to guide the amount of correction. CT-scans were done before and after the procedures in all bones and the amount of correction was determined to compare the precision of the two techniques. Electromagnetic tracking resulted in a precision of 2.25° ± 1.77° for derotation and 1.38° ± 1.29° for extension, while precision for the conventional method was significantly lower. There was a significant relationship between goniometer measurement deviation and the absolute angle change for derotation and extension measurements with larger deviations for greater angle changes. For the electro-magnetic tracking, this correlation was observed only for derotation measurement. Electro-magnetic tracking represents an accurate method to control complex, multiplanar corrective osteotomies with superior precision in comparison to conventional goniometric measurement. Further research is needed to investigate the in-vivo accuracy and the effects on clinical outcome.</p>","PeriodicalId":16650,"journal":{"name":"Journal of Orthopaedic Research®","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502392","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}
Ausberto Velasquez Garcia, Jennifer M Oettinger, Adam J Wentworth, Hiroki Nishikawa, Grace K Chaney, James S Fitzsimmons, Jonathan M Morris, Shawn W O'Driscoll
{"title":"Automated coordinate system estimation: A preliminary step toward computer-assisted radial head arthroplasty planning.","authors":"Ausberto Velasquez Garcia, Jennifer M Oettinger, Adam J Wentworth, Hiroki Nishikawa, Grace K Chaney, James S Fitzsimmons, Jonathan M Morris, Shawn W O'Driscoll","doi":"10.1002/jor.25996","DOIUrl":"https://doi.org/10.1002/jor.25996","url":null,"abstract":"<p><p>The success of radial head arthroplasty (RHA) relies on the design of the implant and precision of the surgical technique, with preoperative planning potentially playing a crucial role. The accurate establishment of a patient-specific anatomical coordinate system (ACS) is essential for this planning process. This study tested the hypothesis that an innovative automated method would be an accurate, reliable, and efficient framework to determine the ACS of the proximal radius, which would be a step toward improving the precision of RHA planning. We used advanced computational techniques to analyze 50 forearm CT scans, comparing the accuracy, reproducibility, reliability, and efficiency of the automated method with manually derived ACS using expert observers as benchmarks. The results showed that the automated approach was more accurate in identifying anatomical landmarks, with smaller mean distance discrepancies (0.6 mm) than manual observers (1 mm). Its reproducibility was also superior, with narrower reproducibility limits, particularly for ulnar notch landmarks (0.6 to 0.8 mm compared to manual selection 1.2 to 1.4 mm) (p = .01). In addition, the limits of agreement and the mean absolute rotational and translational differences of the axes were narrower for the automated method, which also reduced the construction time to an average of 46 s compared to 150 s manually (p < .001). These findings suggest that the automated method has the potential to enhance the accuracy and efficiency of preoperative and postoperative computer-assisted procedures for RHA. Further research is needed to fully understand the utility of this automated system for enhancing RHA computer-assisted surgical planning.</p>","PeriodicalId":16650,"journal":{"name":"Journal of Orthopaedic Research®","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502391","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}
Sofia Hidalgo Perea, Tyler J Uppstrom, Kenneth M Lin, Craig E Klinger, Timothy G Bromage, Kevin G Shea, Daniel W Green, Scott A Rodeo
{"title":"An ultrastructure analysis of the developing human anterior cruciate ligament tibial enthesis.","authors":"Sofia Hidalgo Perea, Tyler J Uppstrom, Kenneth M Lin, Craig E Klinger, Timothy G Bromage, Kevin G Shea, Daniel W Green, Scott A Rodeo","doi":"10.1002/jor.25999","DOIUrl":"https://doi.org/10.1002/jor.25999","url":null,"abstract":"<p><p>This study aimed to investigate the ultrastructural anatomy of the developing ACL tibial enthesis. We hypothesized that enthesis architecture would progressively mature and remodel, eventually resembling that of the adult by the early postnatal stage. Five fresh-frozen human pediatric cadaveric knees aged 1-36 months underwent anatomical dissection to harvest the ACL insertion and underlying tibial chondroepiphysis. The samples were prepared for scanning electron microscopy (SEM) to examine the ultrastructural anatomy of the enthesis and underwent histological staining for circular polarized light (CPL) and light microscopy imaging. SEM analysis of the 1- and 8-month-old samples revealed a shallow interdigitation between the dense fibrous (ligamentous) tissue and unmineralized chondrogenic tissues, with a minimal transition zone. By 11-month, a more complex transition zone was present. By age 19- and 36-month-old, a progressively more complex and defined fibrocartilage zone was observed. CPL analysis revealed distinct collagen fiber continuity, alignment, and organization changes over time. By 19 and 36 months, the samples exhibited complex fiber arrangements and a progression toward uniform fiber orientation. Similarly, histological analysis demonstrated progressive remodeling of the enthesis with increasing age. Our results suggest that the ACL enthesis of the developing knee begins to mimic that of an adult as early as 19 months of age, as a more complex transition between ligamentous and chondro-epiphyseal tissue can be appreciated. We hypothesize that the observed changes are likely due to mechanical loading of the enthesis with the onset of weightbearing. Future investigations of ACL reconstruction and repair will benefit from improved understanding of the chondro-epiphyseal/ACL regions.</p>","PeriodicalId":16650,"journal":{"name":"Journal of Orthopaedic Research®","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502390","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 - Editorial Board and TOC","authors":"","doi":"10.1002/jor.25620","DOIUrl":"https://doi.org/10.1002/jor.25620","url":null,"abstract":"","PeriodicalId":16650,"journal":{"name":"Journal of Orthopaedic Research®","volume":"42 11","pages":"2353-2357"},"PeriodicalIF":2.1,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jor.25620","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142443548","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 - Cover","authors":"","doi":"10.1002/jor.25621","DOIUrl":"https://doi.org/10.1002/jor.25621","url":null,"abstract":"","PeriodicalId":16650,"journal":{"name":"Journal of Orthopaedic Research®","volume":"42 11","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jor.25621","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142443547","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}
Nienke N de Laat, Lennard A Koster, Berend C Stoel, Rob G H H Nelissen, Bart L Kaptein
{"title":"Accuracy and precision of Volumetric Matching Micromotion Analysis (V3MA) is similar to RSA for tibial component migration in TKA.","authors":"Nienke N de Laat, Lennard A Koster, Berend C Stoel, Rob G H H Nelissen, Bart L Kaptein","doi":"10.1002/jor.25989","DOIUrl":"https://doi.org/10.1002/jor.25989","url":null,"abstract":"<p><p>Radiostereometric analysis (RSA) is the current gold standard to determine implant migration, but it requires bone markers and special equipment. Therefore, we developed VoluMetric Matching Micromotion Analysis (V3MA), a software program for Computed Tomography-based radiostereometric analysis (CT-RSA). This study aimed to determine the accuracy and precision of V3MA in vitro compared to RSA and provide a clinical proof of concept. The accuracy (RMSE (Root Mean Squared Error)) and precision (SD (standard deviation)) of V3MA were compared to RSA. A tibial component was placed in 21 different positions within a cadaveric bone to assess accuracy. For precision, a total of 20 repeated zero-migration examinations from 4 cadaveric bones with cemented tibial components were performed. In 6 total knee arthroplasty (TKA) patients 1 to 5 year migration was measured with V3MA and RSA. V3MA accuracy ranged between 0.02 and 0.09 mm for translations and was 0.01° for internal-external rotations. For RSA, the accuracy ranged between 0.03 and 0.09 mm for translations and was 0.09° for internal-external rotations. V3MA precision ranged between 0.01 and 0.06 mm for translations and 0.02 to 0.07° for rotations. RSA precision ranged between 0.00 and 0.06 mm for translations and 0.04 to 0.25° for rotations. V3MA was successful in 6 clinical cases and no systematic bias was present. In conclusion, the accuracy and precision of V3MA were similar to RSA. Therefore, V3MA is a promising alternative to RSA in migration measurements of tibial components in TKA.</p>","PeriodicalId":16650,"journal":{"name":"Journal of Orthopaedic Research®","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468214","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}
Siqi Zhang, Guanying Gao, Xiang Zhou, Cancan Du, Yichuan Zhu, Tong-Chuan He, Yan Xu
{"title":"Development of a novel rabbit model for femoroacetabular impingement through surgically induced acetabular overcoverage.","authors":"Siqi Zhang, Guanying Gao, Xiang Zhou, Cancan Du, Yichuan Zhu, Tong-Chuan He, Yan Xu","doi":"10.1002/jor.25994","DOIUrl":"https://doi.org/10.1002/jor.25994","url":null,"abstract":"<p><p>There is a lack of validated small animal models for femoroacetabular impingement (FAI) that induce intra-articular lesions and cause osteoarthritis (OA) progression. The gene expression profile of articular cartilage in patients with FAI has not been characterized in animal studies. The purpose of this study is to describe a novel rabbit model for FAI with validated induction of intra-articular lesions and OA progression and to characterize the gene expression pattern in impinged cartilage using this model. Thirty 6-month-old New Zealand White rabbits underwent unilateral endobutton implant placement at the acetabular rim to surgically create overcoverage. Radiological assessment confirmed secure placement of endobutton at the acetabular rim for all operated hips with a mean alteration in lateral center-edge angle (ΔLCEA) of 16.2 ± 6.6°. Gross inspection revealed secondary cartilage injuries in the anterosuperior region of the femoral head for the operated hips. Cartilage injuries were shown to exacerbate with increased impingement duration, as demonstrated by the modified Outerbridge scores and Mankin scores. Immunostaining and quantitative real-time polymerase chain reaction revealed elevated expression of inflammatory, anabolic and catabolic genes in impinged cartilage. RNA sequencing analysis of cartilage tissue revealed a distinct transcriptome profile and identified C-KIT, CD86, and CD68 as central markers. Our study confirmed that the novel rabbit FAI model created acetabular overcoverage and produced articular cartilage injury at the impingement zone. Cartilage from the impingement zone demonstrated a heightened metabolic state, corroborating with the gene expression pattern observed in patients with FAI.</p>","PeriodicalId":16650,"journal":{"name":"Journal of Orthopaedic Research®","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468215","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}
Gabi Schwartz, Samir Rana, Alicia R Jackson, Clarissa Leñero, Thomas M Best, Dimitrios Kouroupis, Francesco Travascio
{"title":"Human mesenchymal stem/stromal cell-derived extracellular vesicle transport in meniscus fibrocartilage.","authors":"Gabi Schwartz, Samir Rana, Alicia R Jackson, Clarissa Leñero, Thomas M Best, Dimitrios Kouroupis, Francesco Travascio","doi":"10.1002/jor.25993","DOIUrl":"https://doi.org/10.1002/jor.25993","url":null,"abstract":"<p><p>Extracellular vesicles (EVs) derived from endometrial-derived mesenchymal stem/stromal cells (eMSC) play a crucial role in tissue repair due to their immunomodulatory and reparative properties. Given these properties, eMSC EVs may offer potential benefits for meniscal repair. The meniscus, being partly vascularized, relies on diffusivity for solute trafficking. This study focuses on EVs transport properties characterization within fibrocartilage that remains unknown. Specifically, EVs were isolated from Crude and CD146<sup>+</sup> eMSC populations. Green fluorescence-labeled EVs transport properties were investigated in three structurally distinct layers (core, femoral, and tibial surfaces) of porcine meniscus. Diffusivity was measured via custom fluorescence recovery after photobleaching (FRAP) technique. Light spectrometry was used to determine EVs solubility. Both Crude and CD146<sup>+</sup> eMSC EVs exhibited high purity (>90% CD63CD9 marker expression) and an average diffusivity of 10.924 (±4.065) µm²/s. Importantly, no significant difference was observed between Crude and CD146<sup>+</sup> eMSC EV diffusivity on the meniscal layer (p > 0.05). The mean partitioning coefficient was 0.2118 (±0.1321), with Crude EVs demonstrating significantly higher solubility than CD146<sup>+</sup> EVs (p < 0.05). In conclusion, this study underscores the potential of both Crude and CD146<sup>+</sup> eMSC EVs to traverse all layers of the meniscus, supporting their capacity to enhance delivery of orthobiologics for cartilaginous tissue healing.</p>","PeriodicalId":16650,"journal":{"name":"Journal of Orthopaedic Research®","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468145","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}