{"title":"Issue Information - Cover","authors":"","doi":"10.1002/jor.25885","DOIUrl":"https://doi.org/10.1002/jor.25885","url":null,"abstract":"","PeriodicalId":16650,"journal":{"name":"Journal of Orthopaedic Research®","volume":"43 4","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jor.25885","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143595216","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.25884","DOIUrl":"https://doi.org/10.1002/jor.25884","url":null,"abstract":"","PeriodicalId":16650,"journal":{"name":"Journal of Orthopaedic Research®","volume":"43 4","pages":"715-718"},"PeriodicalIF":2.1,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jor.25884","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143595217","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}
Rebecca M Irwin, Matthew Brown, Matthew F Koff, Chang H Lee, Elisabeth Lemmon, Hun Jin Jeong, Susana P Simmonds, Jennifer L Robinson, Andreas M Seitz, Petri Tanska, Ruben J Trujillo, Jay M Patel, Chathuraka T Jayasuriya, Donna Pacicca
{"title":"Generating New Meniscus Therapies via Recent Breakthroughs in Development, Model Systems, and Clinical Diagnostics.","authors":"Rebecca M Irwin, Matthew Brown, Matthew F Koff, Chang H Lee, Elisabeth Lemmon, Hun Jin Jeong, Susana P Simmonds, Jennifer L Robinson, Andreas M Seitz, Petri Tanska, Ruben J Trujillo, Jay M Patel, Chathuraka T Jayasuriya, Donna Pacicca","doi":"10.1002/jor.26066","DOIUrl":"https://doi.org/10.1002/jor.26066","url":null,"abstract":"<p><p>Over 850,000 surgeries are performed to treat meniscal injuries each year in the United States. Even with repair, patients are likely to develop osteoarthritis (OA) within the next two decades. There is a pressing clinical need to improve meniscal repair procedures to restore tissue function and prevent joint degeneration later in life. Here we present a review of recently published articles (2020-2024) spanning basic science, translational, and clinical studies to highlight new advances in meniscus research across development, animal models, finite element models, and clinical interventions. Key progenitor cell populations and vascularity changes have been identified in human meniscus tissue development, aging, and degeneration with implications for novel tissue repair strategies. The use of animal and finite element models has expanded our understanding of meniscus tissue function and evaluated new therapies in preclinical studies. Further, advances in clinical diagnostics with machine learning models and surgical techniques have shed light on evidence-based practices for improving patient outcomes. We discuss across multiple length scales (micro-, meso-, macro-) the structure-function relationship of the meniscus in development and disease, recent advances in models and tools to study the meniscus, knowledge gaps in the field, persisting challenges in clinical treatments and assessments, and the translation of basic science therapies into the clinic.</p>","PeriodicalId":16650,"journal":{"name":"Journal of Orthopaedic Research®","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605246","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}
Susumu Wada, Takayuki Fujii, Camila B Carballo, Yuki Suzuki, Zhe Song, Yake Liu, Xueying Zhang, Brett J Croen, Reyna Bhandari, Xiang-Hua Deng, Scott A Rodeo
{"title":"Remodeling Process of the Tendon Graft After Anterior Cruciate Ligament Reconstruction: Comprehensive Analysis With RNA Sequencing in a Murine Model.","authors":"Susumu Wada, Takayuki Fujii, Camila B Carballo, Yuki Suzuki, Zhe Song, Yake Liu, Xueying Zhang, Brett J Croen, Reyna Bhandari, Xiang-Hua Deng, Scott A Rodeo","doi":"10.1002/jor.26065","DOIUrl":"https://doi.org/10.1002/jor.26065","url":null,"abstract":"<p><p>The tendon graft is known to undergo a remodeling process after anterior cruciate ligament (ACL) reconstruction. However, little is known about the transcriptional profile of this process. The aim of the present study is to identify differentially expressed genes inside the remodeling ACL graft in the early phase after ACL reconstruction in our murine model using RNA sequencing (RNAseq). Fifty four male C57BL/6 mice were used in this study. The mice were euthanized at 1, 2, and 4 weeks after surgery and used for histological evaluations and RNAseq of the tendon graft. Histologically, there was a progressive decrease in the tendon-bone interface gap space and increased tissue continuity between the grafted tendon and the bone tunnel over time. At 1 and 2 weeks after surgery, cell increase and loss of collagen fiber organization inside the tendon graft were observed. RNAseq showed that genes related to inflammation, matrix metalloproteinases, bone metabolism, chemokines and signaling pathways were upregulated at 1 and 2 weeks after surgery compared to the control group (p < 0.0001). Our transcriptional profiling data suggests that expression of inflammatory mediators and bone remodeling genes may play an important role in the early events in graft-to-bone healing. Further validation at the protein level is necessary to draw firm conclusions about the role of these mediators in graft remodeling and healing. Understanding the remodeling process of the grafted tendons may lead to the identification of new approaches to improve clinical outcomes after ACL reconstruction.</p>","PeriodicalId":16650,"journal":{"name":"Journal of Orthopaedic Research®","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596957","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":"Extensive Periosteal Injury During Fracture Induces Long-Term Pain in Mice.","authors":"Jiaoni Li, Yu-Ru Vernon Shih, Huchen Tao, Mitchell Negus, Jeffrey Bohrer Guerra, Shyni Varghese","doi":"10.1002/jor.26067","DOIUrl":"https://doi.org/10.1002/jor.26067","url":null,"abstract":"<p><p>Bone fractures pose a significant public health challenge, often necessitating surgical interventions to facilitate bone healing and functional recovery. Sensory nerve fibers innervate various compartments of the bone tissue, with the periosteum exhibiting the most extensive innervation that is susceptible to injury during trauma. Despite its importance, the effect of injured periosteum on fracture pain remains unknown. This study examines the impact of extensive periosteal injury on fracture pain by using a mouse model. Periosteal injury is induced by mechanical resection during unilateral transverse fracture and compared to transverse fractures with no periosteal injury. Our results demonstrate that extensive periosteal injury induces severe and long-term pain, as assessed by von Frey and dynamic weight bearing measurements, for up to 12 weeks postfracture. Immunofluorescence staining revealed an increase in local neurofilament heavy polypeptide (NF200 +) nerve innervation and an elevated number of calcitonin gene-related peptide (CGRP +) expressing neurons in the dorsal root ganglion (DRG). Additionally, flow cytometric analyses revealed increased presence of myeloid immune cells in the DRG. Furthermore, bone healing in fractures with extensive periosteal injury exhibited reduced callus size at all time points as assessed by Faxitron X-ray imaging. This study describes a previously unknown effect of extensive periosteal injury in exacerbating fracture pain and establishes a potential model to study long-term orthopedic fracture pain.</p>","PeriodicalId":16650,"journal":{"name":"Journal of Orthopaedic Research®","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596956","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}
Rodrigo Labat Marcos, Mateus Moura Evaristo, Patrícia de Almeida-Mattos, Cristina Nunes Capeloa, José Maria Miguel Aguilera Cantero, Renato Araújo Prates, José Antônio Silva Junior, Andrey Jorge Serra, Leonardo Longo, Nivaldo Antonio Parizotto, Rodrigo Álvaro Brandão Lopes Martins
{"title":"Photobiomodulation Controls the Expression of Lipoxin Receptors, Promoting the Resolution of the Inflammatory Process in an Experimental Tendinitis Model.","authors":"Rodrigo Labat Marcos, Mateus Moura Evaristo, Patrícia de Almeida-Mattos, Cristina Nunes Capeloa, José Maria Miguel Aguilera Cantero, Renato Araújo Prates, José Antônio Silva Junior, Andrey Jorge Serra, Leonardo Longo, Nivaldo Antonio Parizotto, Rodrigo Álvaro Brandão Lopes Martins","doi":"10.1002/jor.26063","DOIUrl":"https://doi.org/10.1002/jor.26063","url":null,"abstract":"<p><p>Tendinopathies are a significant global health issue due to their detrimental effects on mobility and quality of life. Pharmacological treatments, although widely used for pain management, often demonstrate limited efficacy. Photobiomodulation therapy (PBM) has emerged as a potential adjunctive treatment due to its capacity to modulate inflammation and alleviate pain. Nevertheless, further research is required to elucidate its mechanisms of action, particularly concerning the resolution of the inflammatory process. This study aimed to evaluate the effects of PBM on inflammation control in an experimental tendinitis model by analyzing inflammatory infiltrate, myeloperoxidase (MPO) activity, the expression of inflammatory and resolution markers (TNF-α, TGF-β, COX-2, and ALX), and protein levels of PGE2 and COX-2 in rat Achilles tendons with type I collagen-induced tendinitis. Male Wistar rats were randomized into five groups: healthy control (CTL), untreated tendinitis (NT), PBM-treated tendinitis (830 nm; 3 J; 30 mW; 64 J/cm²), or tendinitis treated with sodium diclofenac (DIC; 1 mg/kg IM). After 2 or 12 h, tissues and blood were collected for biochemical and histological analysis. The NT group exhibited increased inflammatory infiltrate, MPO activity (p < 0.001), COX-2, TNF-α (p < 0.001), and PGE2 expression (p < 0.01) but lacked ALX receptor upregulation. PBM and DIC treatments significantly reduced inflammatory infiltrate and MPO activity (PBM: p < 0.001; DIC: p < 0.01). PBM enhanced ALX and TGF-β expression (p < 0.001) and maintenance of COX-2 similar to the NT group, suggesting lipoxin involvement in inflammation resolution. These findings highlight PBM as a promising therapy for tendinopathies by targeting both inflammatory and resolution pathways.</p>","PeriodicalId":16650,"journal":{"name":"Journal of Orthopaedic Research®","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143567436","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}
Tianhao Wu, Lisha Zhu, Min Yu, Xinjia Cai, Liyuan Chen, He Zhang, Xiaolan Wu, Chengye Ding, Hangbo Liu, Shiying Zhang, Chang Li, Xinmeng Shi, Yu Wang, Yan Liu
{"title":"AMPK Signaling Pathway Regulates Tendon Regeneration via Fatty Acid Metabolism.","authors":"Tianhao Wu, Lisha Zhu, Min Yu, Xinjia Cai, Liyuan Chen, He Zhang, Xiaolan Wu, Chengye Ding, Hangbo Liu, Shiying Zhang, Chang Li, Xinmeng Shi, Yu Wang, Yan Liu","doi":"10.1002/jor.26061","DOIUrl":"https://doi.org/10.1002/jor.26061","url":null,"abstract":"<p><p>Tendon and ligament injuries are the most common musculoskeletal injuries, and their regeneration is a complex process due to the poor natural healing ability of these tissues. The current therapies for tendon repair are limited in efficacy and their cellular and molecular mechanisms remain unclear. In this study, we identified AMP-activated protein kinase (AMPK) as a markedly upregulated factor in newborn tendons with high regenerative capacity. Both in vivo and in vitro experiments demonstrated that treatment with dorsomorphin, an AMPK inhibitor, significantly decreased the tendon healing potential. Further analyses revealed that carnitine palmitoyltransferase 1A, a key enzyme, is a putative downstream target of AMPK and is closely associated with the proliferation and tenogenic differentiation of tendon stem/progenitor cells. Collectively, we highlight the essential role of AMPK in tendon repair and propose a potential therapeutic intervention for tendon injuries.</p>","PeriodicalId":16650,"journal":{"name":"Journal of Orthopaedic Research®","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537320","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}
Samantha A Hefferan, Carina L Blaker, Dylan M Ashton, Christopher B Little, Elizabeth C Clarke
{"title":"Structural Variations of Tendons: A Systematic Search and Narrative Review of Histological Differences Between Tendons, Tendon Regions, Sex, and Age.","authors":"Samantha A Hefferan, Carina L Blaker, Dylan M Ashton, Christopher B Little, Elizabeth C Clarke","doi":"10.1002/jor.26060","DOIUrl":"https://doi.org/10.1002/jor.26060","url":null,"abstract":"<p><p>Tendons are force-transmitting structures which facilitate musculoskeletal functioning. Characterizing variations between different anatomical tendons, regions within tendons, as well as between the sexes and with age can improve understanding of tendon physiology and pathology. A systematic search of the literature was conducted to identify and summarize microscopic structural (histological) variations in normal/healthy tendons in relation to these variables (Tendon, Region, Age, Sex, and Other). Regional differences within individual tendons have been investigated in numerous studies, however investigations comparing histological variations between a range of different tendons are sparse, with most focusing on a few select tendons. When injured, ageing tendons typically have a greater degree of pathological changes than younger tendons, but few studies have documented variations in tendon histology throughout typical (uninjured) ageing or across large age spans. Similarly, sex-related observations of tendon structure are underreported. This narrative review summarizes studies on these topics and explores interactions between these variables, as well as the implications of these in the context of selecting control samples for studies of tendon pathology. Future studies should endeavour to improve knowledge of tendon structural variations-specifically focusing on normal tendons-to facilitate understanding of tendon structure-function relationships, physiological mechanisms involved in tendon damage/healing, and to aid clinical research and practice.</p>","PeriodicalId":16650,"journal":{"name":"Journal of Orthopaedic Research®","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143516053","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}
Markus Laubach, Agathe Bessot, Siamak Saifzadeh, Craig Simon, Wolfgang Böcker, Nathalie Bock, Dietmar W Hutmacher, Jacqui McGovern
{"title":"Assessing Cardiopulmonary Safety of Intramedullary Bone Graft Harvesting: A Comparative Study of the RIA 2 System and the ARA Concept.","authors":"Markus Laubach, Agathe Bessot, Siamak Saifzadeh, Craig Simon, Wolfgang Böcker, Nathalie Bock, Dietmar W Hutmacher, Jacqui McGovern","doi":"10.1002/jor.26059","DOIUrl":"https://doi.org/10.1002/jor.26059","url":null,"abstract":"<p><p>The management of large osseous defects requires innovative intramedullary bone graft harvesting techniques to optimize healing while minimizing complications. Intramedullary bone graft harvesting is, however, associated with potential cardiopulmonary adverse events due to embolic phenomena and systemic inflammation. This study compares the newly introduced aspirator + reaming-aspiration (ARA) concept with the established second-generation Reamer-Irrigator-Aspirator (RIA 2) system, focusing on cardiopulmonary safety in a non-fracture sheep femur model. Sixteen female Merino sheep underwent intramedullary bone grafting using either the RIA 2 system or the ARA concept. The primary outcomes measured were blood loss, hemodynamic parameters, pulmonary function via the Horovitz index, and systemic inflammatory responses postprocedure. Findings revealed minimal and comparable blood loss between the two groups (p = 0.55). Additionally, no significant differences were found in hemodynamic stability (all p ≥ 0.05), pulmonary function (p = 0.96), or systemic inflammation (all p ≥ 0.10) between the RIA 2 system and ARA concept groups, demonstrating the comparable safety profile of the ARA concept to the RIA 2 system. In conclusion, the ARA concept emerges as a viable and effective alternative to the RIA 2 system for intramedullary bone graft harvesting, with similar safety profiles. These promising results advocate for further clinical trials to validate the utility of the ARA concept in human patients.</p>","PeriodicalId":16650,"journal":{"name":"Journal of Orthopaedic Research®","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143501688","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}
Bernhard Guggenberger, Willi Koller, Andreas Habersack, Tanja Kraus, Matthias Sperl, Martin Svehlik, Hans Kainz
{"title":"Impact of Femoral and Tibial Torsion on Patellofemoral Loading in Individuals With Patellofemoral Instability.","authors":"Bernhard Guggenberger, Willi Koller, Andreas Habersack, Tanja Kraus, Matthias Sperl, Martin Svehlik, Hans Kainz","doi":"10.1002/jor.26058","DOIUrl":"https://doi.org/10.1002/jor.26058","url":null,"abstract":"<p><p>Patellofemoral stability is affected by several morphological factors including torsional alignment. To elucidate the impact of factors responsible for the stability of the patellofemoral joint, biomechanical research utilizes the analysis of joint contact forces. At present, there is a paucity of modeling-based research examining the influence of lower limb torsion on patellofemoral joint loading in individuals with patellofemoral instability. The objective of this study was to investigate the impact of the femoral version and tibial torsion on the patellofemoral joint loading. Musculoskeletal simulations were conducted based on 3D motion capture data of 40 individuals with patellofemoral instability using OpenSim. We created three models with different lower limb torsions for each participant: (i) generic torsion, (ii) personalized lower limb (femur and tibia) torsion, and (iii) isolated personalized femoral version model. We correlated femoral version and tibial torsion to differences in patellofemoral joint loading, muscle forces, and lever arms between models. Tibial torsion correlated to differences in mediolateral patellofemoral force (ρ = 0.39), whereas the femoral version showed no significant correlation to the differences in mediolateral patellofemoral force (ρ = 0.01). Notably, when neglecting individual tibial torsion, the femoral version correlated to differences in mediolateral patellofemoral force (ρ = 0.65). The femoral version can increase the lateralizing force on the patella, but this effect diminishes when addressing whole lower limb torsion in musculoskeletal simulations. Studies investigating solely the femoral version should, therefore, be interpreted with caution. Our findings underscore the necessity of evaluating whole lower limb torsion for a comprehensive assessment of its impact on patellofemoral stability and planning treatments. Level of Evidence: Retrospective cohort study, Level III.</p>","PeriodicalId":16650,"journal":{"name":"Journal of Orthopaedic Research®","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143492437","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}