Noreen J. Hickok, Antonia F. Chen, Kordo Saaed, Kenneth Urish, Thomas P. Schaer
{"title":"In memoriam: Paul Stoodley—Tribute to a friend","authors":"Noreen J. Hickok, Antonia F. Chen, Kordo Saaed, Kenneth Urish, Thomas P. Schaer","doi":"10.1002/jor.25955","DOIUrl":"10.1002/jor.25955","url":null,"abstract":"","PeriodicalId":16650,"journal":{"name":"Journal of Orthopaedic Research®","volume":"42 12","pages":"2611-2612"},"PeriodicalIF":2.1,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141988142","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}
Michele Conconi, Nicola Sancisi, Alberto Leardini, Claudio Belvedere
{"title":"The foot and ankle complex as a four degrees-of-freedom system: Kinematic coupling among the foot bones","authors":"Michele Conconi, Nicola Sancisi, Alberto Leardini, Claudio Belvedere","doi":"10.1002/jor.25951","DOIUrl":"10.1002/jor.25951","url":null,"abstract":"<p>Seventy-eight parameters are theoretically needed to describe the relative position and orientation of all the 14 bones in the foot and ankle with respect to a reference bone (foot posture). However, articular contacts and soft tissues introduce kinematic coupling, reducing the number of the foot degrees-of-freedom (DOF). This study aims at providing quantification and definition of these couplings. The foot posture was measured in vitro through a series of computed tomography scans, spanning the whole range of foot dorsi/plantar flexion and pronation/supination, also considering the effect of weightbearing. The envelope of foot postures was investigated by means of principal component analysis. The foot and ankle motion were well described with four principal sets of kinematic couplings, that is, synergies. One synergy covers the independent motion of the ankle, while three synergies describe the foot motion. The first foot synergy shows all the bones rotating approximatively about a common axis, mapping the foot abduction/adduction about the Chopart joint. The second foot synergy results in a spherical motion, whose center is located between lateral cuneiform and navicular bone, mapping the foot pronation/supination. The third foot synergy maps the opening of the foot arches during the load acceptance. The foot and ankle complex can thus be described as a four DOF system, whose motion is the result of the linear combination of four synergies. Significance: Synergies reveal the contribution of each bone to the three-dimensional foot posture, providing a compact representation of the motion of the foot and ankle complex, improving the comprehension of its physiology.</p>","PeriodicalId":16650,"journal":{"name":"Journal of Orthopaedic Research®","volume":"42 12","pages":"2761-2772"},"PeriodicalIF":2.1,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141916995","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}
Eros Montin, Richard Kijowski, Thomas Youm, Riccardo Lattanzi
{"title":"Radiomics features outperform standard radiological measurements in detecting femoroacetabular impingement on three-dimensional magnetic resonance imaging","authors":"Eros Montin, Richard Kijowski, Thomas Youm, Riccardo Lattanzi","doi":"10.1002/jor.25952","DOIUrl":"10.1002/jor.25952","url":null,"abstract":"<p>Femoroacetabular impingement (FAI) is a cause of hip pain and can lead to hip osteoarthritis. Radiological measurements obtained from radiographs or magnetic resonance imaging (MRI) are normally used for FAI diagnosis, but they require time-consuming manual interaction, which limits accuracy and reproducibility. This study compares standard radiologic measurements against radiomics features automatically extracted from MRI for the identification of FAI patients versus healthy subjects. Three-dimensional Dixon MRI of the pelvis were retrospectively collected for 10 patients with confirmed FAI and acquired for 10 healthy subjects. The femur and acetabulum were segmented bilaterally and associated radiomics features were extracted from the four MRI contrasts of the Dixon sequence (water-only, fat-only, in-phase, and out-of-phase). A radiologist collected 21 radiological measurements typically used in FAI. The Gini importance was used to define 9 subsets with the most predictive radiomics features and one subset for the most diagnostically relevant radiological measurements. For each subset, 100 Random Forest machine learning models were trained with different data splits and fivefold cross-validation to classify healthy subjects versus FAI patients. The average performance among the 100 models was computed for each subset and compared against the performance of the radiological measurements. One model trained using the radiomics features datasets yielded 100% accuracy in the detection of FAI, whereas all other radiomics features exceeded 80% accuracy. Radiological measurements yielded 74% accuracy, consistent with previous work. The results of this preliminary work highlight for the first time the potential of radiomics for fully automated FAI diagnosis.</p>","PeriodicalId":16650,"journal":{"name":"Journal of Orthopaedic Research®","volume":"42 12","pages":"2796-2807"},"PeriodicalIF":2.1,"publicationDate":"2024-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141913042","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}
Giselle Kaneda, Dave Huang, Nathalie Pham, Alfonso R. Gonzalez, Wafa Tawackoli, Seunghwan Lee, Miyako Suzuki, Trevor J. Nelson, Juliane D. Glaeser, Magali Millecamps, Laura S. Stone, Dmitriy Sheyn, Melodie F. Metzger
{"title":"Exercise improves load bearing bone structural properties in female secreted protein acidic and rich in cysteine (SPARC) null mice but not in males","authors":"Giselle Kaneda, Dave Huang, Nathalie Pham, Alfonso R. Gonzalez, Wafa Tawackoli, Seunghwan Lee, Miyako Suzuki, Trevor J. Nelson, Juliane D. Glaeser, Magali Millecamps, Laura S. Stone, Dmitriy Sheyn, Melodie F. Metzger","doi":"10.1002/jor.25950","DOIUrl":"10.1002/jor.25950","url":null,"abstract":"<p>Secreted protein acidic and rich in cysteine (SPARC) is the most abundant glycoprotein in bone and is thought to play a critical role in bone remodeling and homeostasis. However, the effect of SPARC in relation to gender and exercise on bone quality is not well understood. The purpose of this study was to quantify differences in the structural and biomechanical properties between calvarial and femoral bone from male and female wild-type (WT) and SPARC null (SPARC<sup>(−/−)</sup>) mice as well as the ability of exercise to rescue bone health. Male and female WT and transgenic SPARC<sup>(−/−)</sup> mice were given either a fixed or rotating running wheel for exercise. Bone structural, biomechanical, and morphological parameters were quantified using micro computed tomography, push out testing for the calvaria, three-point flexural testing for the femurs, histological and immunofluorescent staining. Similar reductions in structural and biomechanical strength were observed in both male and female SPARC<sup>(−/−)</sup> calvaria, most of which were not significantly affected by exercise. In femurs, SPARC<sup>(−/−)</sup> had a significant effect on structural parameters in both sexes, but was more pronounced in females with some properties being rescued with running. Interestingly, the effect of SPARC<sup>(−/−)</sup> on bone mineral density was only detected in female SPARC<sup>(−/−)</sup> mice, not males, and was subsequently rescued with exercise. This study emphasizes the differences between sexes in WT and SPARC<sup>(−/−)</sup> mice in regard to structural parameters and biomechanical properties<b>.</b> Research into gender differences can help inform and personalize treatment options to more accurately meet patient needs.</p>","PeriodicalId":16650,"journal":{"name":"Journal of Orthopaedic Research®","volume":"42 12","pages":"2725-2734"},"PeriodicalIF":2.1,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141893694","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}
Katherine Collins, Caroline Lisee, Elizabeth Bjornsen, Cortney Armitano-Lago, Ashley Buck, Christin Büttner, Troy Blackburn, Todd A. Schwartz, Natália Favoreto, Jeffrey T. Spang, Jason R. Franz, Brian Pietrosimone
{"title":"Peak vertical ground reaction force used to identify sub-groups of individuals with differing biomechanical gait profiles post-anterior cruciate ligament reconstruction","authors":"Katherine Collins, Caroline Lisee, Elizabeth Bjornsen, Cortney Armitano-Lago, Ashley Buck, Christin Büttner, Troy Blackburn, Todd A. Schwartz, Natália Favoreto, Jeffrey T. Spang, Jason R. Franz, Brian Pietrosimone","doi":"10.1002/jor.25948","DOIUrl":"10.1002/jor.25948","url":null,"abstract":"<p>Lesser peak vertical ground reaction force (vGRF) has been widely reported among individuals with anterior cruciate ligament reconstruction (ACLR). Peak vGRF remains less than uninjured controls and relatively stable during the first year following ACLR. However, it is unknown whether there are subgroups of individuals exhibiting consistently greater peak vGRF in the first 6-months following ACLR and if individuals with consistently greater peak vGRF exhibit kinematic and kinetic gait differences compared to individuals with low vGRF. The purpose of this study was to determine if distinct clusters exist based upon magnitude of peak vGRF 2- and 6-months post-ACLR. Subsequently, we explored between cluster differences in vGRF, knee flexion angle, and sagittal and frontal plane knee kinetics throughout stance between clusters. Forty-three individuals (58.1%female, 21.4 ± 4.4 years-old, 95.3% patellar-tendon autograft) completed five gait trials at their habitual walking speed 2- and 6-months post-ACLR. A single K-means cluster analysis was used to identify clusters of individuals based on peak vGRF at 2- and 6-months post-ACLR. Functional waveform analyses were used to compare gait outcomes between clusters with and without controlling for gait speed and age. We identified two clusters that included a subgroup with high vGRF (<i>n</i> = 16) and low vGRF (<i>n</i> = 27). The cluster with high vGRF demonstrated greater vGRFs, knee flexion angles, and knee extension moments during early stance as compared to the low vGRF cluster 2- and 6-months post-ACLR. Individuals with peak vGRF ≥1.02 times body-weight 2-months post-ACLR had 35.4 times greater odds of being assigned to the high vGRF cluster.</p>","PeriodicalId":16650,"journal":{"name":"Journal of Orthopaedic Research®","volume":"42 12","pages":"2714-2724"},"PeriodicalIF":2.1,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141897560","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}
Hans Christian Rasmussen, Pelle Hanberg, Johanne G. Lilleøre, Elisabeth K. Petersen, Magnus A. Hvistendahl, Andrea R. Jørgensen, Maiken Stilling, Mats Bue
{"title":"Penicillin concentrations in bone and subcutaneous tissue: A porcine microdialysis study comparing oral and intravenous treatment","authors":"Hans Christian Rasmussen, Pelle Hanberg, Johanne G. Lilleøre, Elisabeth K. Petersen, Magnus A. Hvistendahl, Andrea R. Jørgensen, Maiken Stilling, Mats Bue","doi":"10.1002/jor.25947","DOIUrl":"10.1002/jor.25947","url":null,"abstract":"<p>Penicillin is available in both an oral (penicillin V) and intravenous formulation (penicillin G), theoretically allowing for a safe transition between the two. However, the use of oral penicillin remains a topic of debate due to low and variable bioavailability. This study aimed to assess the time for which the free penicillin concentration exceeded targeted minimum inhibitory concentrations for <i>Staphylococcus aureus</i> and <i>Streptococcus</i> species (0.125, 0.25, and 0.5 mg/L) in cancellous bone and subcutaneous tissue after intravenous penicillin and oral penicillin administration. 12 female pigs (68–75 kg) were assigned, according to local standard clinical regimes, to either intravenous penicillin (1.2 g) or oral penicillin (0.8 g) treatment every 6 h over an 18 h period. Microdialysis catheters were placed for sampling in tibial cancellous bone and adjacent subcutaneous tissue. Data was dynamic/continually collected in the first dosing interval (0–6 h), simulating a prophylactic situation, and the third dosing interval (12–18 h), simulating a therapeutic setting. Plasma samples were collected for reference. For all investigated targets, intravenous treatment resulted in a longer mean time above relevant minimum inhibitory concentrations in cancellous bone during the first dosing interval, and in both cancellous bone and subcutaneous tissue during the third dosing interval compared to oral treatment. With clinically relevant dosing, intravenous penicillin provides superior exposure compared to oral penicillin in both a prophylactic and therapeutic setting.</p>","PeriodicalId":16650,"journal":{"name":"Journal of Orthopaedic Research®","volume":"42 12","pages":"2844-2851"},"PeriodicalIF":2.1,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jor.25947","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141889545","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}
Carla R. Scanzello, Karen A. Hasty, Christine B. Chung, Timothy M. Griffin, Nick J. Willet, Hollis Krug, Cong-Qiu Chu, David Ewart, Saeed Jerban, Joshua F. Baker, Craig L. Duvall, Jonathan M. Brunger, Jason A. Burdick, Kurt P. Spindler, Hicham Drissi
{"title":"Teaming up to overcome challenges toward translation of new therapeutics for osteoarthritis","authors":"Carla R. Scanzello, Karen A. Hasty, Christine B. Chung, Timothy M. Griffin, Nick J. Willet, Hollis Krug, Cong-Qiu Chu, David Ewart, Saeed Jerban, Joshua F. Baker, Craig L. Duvall, Jonathan M. Brunger, Jason A. Burdick, Kurt P. Spindler, Hicham Drissi","doi":"10.1002/jor.25944","DOIUrl":"10.1002/jor.25944","url":null,"abstract":"<p>As a leading global cause of musculoskeletal-related disability, osteoarthritis (OA) represents a public health urgency. Understanding of disease pathogenesis has advanced substantially in the past decade, yet no disease-modifying therapeutics have advanced to the clinic. To address this challenge, the CARE-AP (Cartilage Repair strategies to alleviate Arthritis Pain) collaborative research team was convened to bring together relevant multidisciplinary expertise and perspectives from across the VA research community nationwide. The first CARE-AP Annual Research Symposium took place (virtually) in February 2022 with roughly 90 participants. A number of innovative and therapeutic strategies were discussed, including siRNA approaches coupled with novel nanoparticle-based delivery systems, cellular engineering approaches to develop reparative cells that can probe the joint environment and respond to disease-specific cues, and novel biofabrication techniques to improve tissue engineering and effect “biological joint replacement.” In addition, challenges and advances in rehabilitation approaches, imaging outcomes, and clinical studies were presented, which were integrated into a framework of recommendations for running “preclinical trials” to improve successful clinical translation.</p>","PeriodicalId":16650,"journal":{"name":"Journal of Orthopaedic Research®","volume":"42 12","pages":"2659-2672"},"PeriodicalIF":2.1,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141893695","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 C. Weinschenk, Blaine M. Oldham, Kishore M. Nagaraja, Faiqa Alam, Richard Samade, Wei Li
{"title":"Three-dimensional-printed femoral diaphysis for biomechanical testing—Optimization and validation","authors":"Robert C. Weinschenk, Blaine M. Oldham, Kishore M. Nagaraja, Faiqa Alam, Richard Samade, Wei Li","doi":"10.1002/jor.25954","DOIUrl":"10.1002/jor.25954","url":null,"abstract":"<p>Polylactic acid (PLA) models of normal human femoral diaphyses were designed using three-dimensional (3D) printing technology to create inexpensive, accessible, and reproducible specimens for flexural biomechanical studies. These models were subjected to three-point bending and their response to loading was characterized. The anisotropic mechanical behavior of the 3D-printed femurs and the influence of printing orientations, infill density, wall layers, resolution, and other printing parameters were explored to develop a design space. The objective of the design space was set to emulate the flexural biomechanical response of the normal human femur bones. Results show the 3D-printed PLA diaphyseal femurs with 5% infill density, two–four wall layers, and a resolution of 200 µm resulted in a flexural strength of 184.8 ± 8.18 MPa. Models with 20% infill density and six wall layers resulted in a flexural modulus of 18.54 ± 0.543 GPa. These results emulate the biomechanical response of the normal human femur, as determined by historical target values derived from prior cadaveric and 3D printing data. With further research, inclusive of modeling the proximal and distal femur and more comprehensive biomechanical testing, 3D-printed femurs may ultimately serve as a cheap, accessible biomechanical resource for surgeons and researchers.</p>","PeriodicalId":16650,"journal":{"name":"Journal of Orthopaedic Research®","volume":"42 12","pages":"2735-2742"},"PeriodicalIF":2.1,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141889547","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}
Jeongkun Lee, Su Hyun Lee, Hyuntae Kim, Seok Won Chung
{"title":"Effect of electrical muscle stimulation on the improvement of deltoid muscle atrophy in a rat shoulder immobilization model","authors":"Jeongkun Lee, Su Hyun Lee, Hyuntae Kim, Seok Won Chung","doi":"10.1002/jor.25943","DOIUrl":"10.1002/jor.25943","url":null,"abstract":"<p>Immobilization following trauma or surgery induces skeletal muscle atrophy, and improvement in the muscle atrophy is critical for successful clinical outcomes. The purpose of this study is to evaluate the effect of electrical muscle stimulation (EMS) on muscle atrophy. The study design is a controlled laboratory study. Eighty rats (56 to establish the deltoid muscle atrophy [DMA] model and 24 to evaluate the effect of EMS on the model) were used. DMA was induced by completely immobilizing the right shoulder of each rat by placing sutures between the scapula and humeral shaft, with the left shoulder as a control. After establishing the DMA model, rats were randomly assigned into three groups: low-frequency EMS (L-EMS, 10 Hz frequency), medium-frequency EMS (M-EMS, 50 Hz frequency), and control (eight rats per group). After 3 weeks, the deltoid muscles of each rat were harvested, alterations in gene expression and muscle cell size were evaluated, and immunohistochemical analysis was performed. DMA was most prominent 3 weeks after shoulder immobilization. Murf1 and Atrogin were significantly induced at the initial phase and gradually decreased at approximately 3 weeks; however, MyoD expressed an inverse relationship with Murf1 and Atrogin. IL6 expression was prominent at 1 week. The time point for the EMS effect evaluation was selected at 3 weeks, when the DMA was the most prominent with a change in relevant gene expression. The M-EMS group cell size was significantly larger than that of L-EMS and control group in both the immobilized and intact shoulders (all <i>p</i> < 0.05), without significant differences between the L-EMS and control groups. The M-EMS group showed significantly lower mRNA expressions of Murf1 and Atrogin and higher expressions of MyoD and Col1A1 than that of the control group (all <i>p</i> < 0.05). In immunohistochemical analysis, similar results were observed with lower Atrogin staining and higher MyoD and Col1A1 staining in the M-EMS group. DMA model was established by complete shoulder immobilization, with the most prominent muscle atrophy observed at 3 weeks. M-EMS improved DMA with changes in the expression of relevant genes. M-EMS might be a solution for strengthening atrophied skeletal muscles and facilitating rehabilitation after trauma or surgery.</p>","PeriodicalId":16650,"journal":{"name":"Journal of Orthopaedic Research®","volume":"42 12","pages":"2634-2645"},"PeriodicalIF":2.1,"publicationDate":"2024-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jor.25943","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141889543","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}
Anna E. Rapp, Angelique Wolter, Dominique Muschter, Susanne Grässel, Annemarie Lang
{"title":"Impact of sensory neuropeptide deficiency on behavioral patterns and gait in a murine surgical osteoarthritis model","authors":"Anna E. Rapp, Angelique Wolter, Dominique Muschter, Susanne Grässel, Annemarie Lang","doi":"10.1002/jor.25949","DOIUrl":"10.1002/jor.25949","url":null,"abstract":"<p>Substance P (SP) and a calcitonin-related gene alpha (αCGRP<sup>−/−</sup>) are implicated in musculoskeletal pain perception and were shown to have different effects on the pathogenesis of osteoarthritis (OA). However, it has not been investigated, whether deficiency for SP or αCGRP impacts pain-related behavior and well-being as well as gait during development of experimental OA. We induced OA in the right knee of wild-type (WT) mice and mice either deficient for SP (tachykinin 1, Tac-1) or αCGRP (male, <i>n</i> = 8 per genotype) by destabilizing the medial meniscus (DMM). We monitored body weight and food and water intake as indicators of wellbeing, determined nest building and composite pain score, and performed CatWalk gait analysis over 12 weeks. Cartilage degeneration was determined by OARSI scoring. The 12-week post-DMM, cartilage degradation in the medial compartment was significantly reduced in Tac1<sup>−/−</sup> mice compared to the WT and to αCGRP<sup>−/−</sup> mice, coinciding with highest unloading of the operated limb in Tac1<sup>−/−</sup>. Behavioral and gait analysis revealed only minor differences between the genotypes. Paw print area was most prominently reduced in Tac1<sup>−/−</sup> over the observation period; at 12 weeks, we found a significant reduction in normalized print area in Tac1<sup>−/−</sup> compared to presurgery and to the WT at the same time-point. Calculated weight bearing was significantly reduced only in Tac1<sup>−/−</sup>. Overall, we observed minor impact of DMM on gait and behavior in the present study. The reduced cartilage damage in the absence of SP might be in part due to reduced loading, however, the mechanism is not clear yet.</p>","PeriodicalId":16650,"journal":{"name":"Journal of Orthopaedic Research®","volume":"42 12","pages":"2673-2682"},"PeriodicalIF":2.1,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141889544","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}