Journal of Orthopaedic Research®最新文献

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.

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.

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.

Rheumatoid arthritis is an autoimmune disease characterized by synovitis, reducing the quality of life of affected individuals through joint swelling and inflammation. Recently, the efficacy of exercise therapy has been proposed for rheumatoid arthritis, but its detailed mechanism is still unclear. Herein, we used a mouse model of human rheumatoid-arthritis pathology to investigate the effects of low-intensity exercise on active arthritis. Twenty-four SKG mice were divided into three groups: "sedentary," "AR" (induced arthritis), and "AREx" (induced arthritis plus low-intensity exercise), with only the AREx group performing treadmill exercise for 4 weeks. During the rearing period, macroscopic arthritis scores were assessed weekly, and histological and bone morphometric analysis of the ankle joints was performed after all interventions. In addition, bulk mRNA sequencing was performed for the synovial-fat pad complex. Consequently, the histological synovitis score showed no change; however, the arthritis score was significantly lower in the AREx group than in the AR group (p < 0.05). The calcaneal and talar bone volumes decreased in the AR group, whereas the AREx group showed no significant change. In the synovial-fat pad complex tissue, the gene expression of inflammatory cytokines decreased in the AREx group compared with the AR group, particularly the suppression of IL6/Jak/Stat3. IHC analysis revealed significantly decreased expression of pro-inflammatory cytokines and increased expression of anti-inflammatory cytokines in the synovium of the AREx group compared with the AR group (p < 0.05). In summary, low-intensity exercise therapy for active rheumatoid arthritis was suggested to have anti-inflammatory effects and to mitigate arthritis exacerbation.

Monitoring muscle atrophy in patients undergoing anterolateral cruciate ligament reconstruction is pivotal for optimizing postoperative recovery. Conventionally, the uninjured contralateral limb serves as the control. However, its relevance in patients with prolonged physical activity hiatus due to knee instability remains uncertain. Our objectives were to compare limbs within a control group by assessing combined force measurements, cross-sectional areas (CSAs), and neuromuscular activation. In addition, we compared the contralateral limb of the surgery group preoperatively to the control group. This prospective controlled study (evidence level 2) included 40 healthy subjects (HG) and 30 patients scheduled for ACL surgery (SG). Both groups underwent identical assessments. The two HG limbs were compared to establish the standard difference for all assessed variables, whereas SG contralateral limb was compared with the mean of the control limbs. For HG, the comparisons between limbs showed no significant differences in muscle strength, CSA area, or electromyographic parameters. Similarly, comparisons between the SG contralateral limb and the mean of HG limbs revealed no significant differences in isometric and dynamic strength for the quadriceps and hamstrings (2.5 ± 0.5 and 2.6 ± 0.9 N.m/kg, and 1.7 ± 0.3 and 1.7 ± 0.4 N.m/kg, respectively). Neuromuscular activation and fatigue patterns were also comparable between groups. CSAs discrepancies were attributed to differences in body mass index between groups. These findings indicate that the contralateral limb in ACL_injured patients is functionally similar to that of healthy controls, supporting its use as a valid reference for monitoring postoperative recovery. Trial Registration: NCT03200678.

To facilitate effective preclinical testing of senescence treatments for osteoarthritis (OA), we have created reliable biomimetic and high-throughput models using aged human joint tissues. Moreover, concerns regarding scalability led to the concurrent development of a high-throughput human in vitro senescence cartilage organoid model. Osteochondral explants and cells for the cartilage organoid model were isolated from patients undergoing joint replacement surgery due to OA. To induce senescence, explants and organoids were subjected to radiation and/or mechanical loading. Samples were harvested; gene expression of relevant senescent and cartilage genes was measured using RT-qPCR, and protein expression was evaluated using histology. A general senescence phenotype was induced by the perturbations, as shown by senescence-associated β-galactosidase staining. In-depth gene expression analysis revealed that hyperphysiological mechanical loading upregulated gene expression of IL8 and SERPINE1, representing aspects of a senescence-associated secretory phenotype (SASP) profile. Irradiation upregulated CDKN1A, encoding p21, and downregulated LMNB1, representing a cell cycle arrest profile with the absence of a SASP response. Combining the two perturbations showed upregulation of CDKN1A, IL8, and SERPINE and downregulation of LMNB1, representing a complementary senescence model. The high-throughput human in vitro cartilage organoid senescence model showed similar effects to the irradiation explant model. In this study, we present a variety of senescence models of human aged chondrocytes that allows for rapid initial screening of anti-senescence compounds in high-throughput, as well as in-depth, characterization of post-mitotic aged chondrocytes prone to OA pathophysiology. This research advances the development of essential therapeutics for OA.

The reparative zone in femoral head osteonecrosis is pivotal for repair; however, the repair response mechanism remains poorly understood. Although neurotrophic nerve growth factor significantly contributes to bone formation in fatigue fractures and ectopic ossification, the relationship between nerve growth factor and the repair response to osteonecrosis remains unexplored. We aimed to elucidate the role of nerve growth factor in osteonecrosis repair. Twenty-seven wholly resected femoral heads diagnosed with Japanese Investigation Committee Stage 3 femoral head osteonecrosis, excluding those with severe collapse, were analyzed. Histopathological diagnosis confirmed the presence of necrotic, reparative, and viable zones in all examined femoral heads. Quantitative evaluation of immunohistological staining, including nerve growth factor, vascular endothelial growth factor, osteocalcin, CD31, and TUBB3, was conducted in each zone. Additionally, micro-computed tomography was used to measure the trabecular bone microstructure in the reparative zone. Nerve growth factor expression was detected in all 27 femoral heads with osteonecrosis, exhibiting a significantly higher prevalence in the reparative zone than in other regions (p < 0.0001). Nerve growth factor was predominantly distributed on the necrotic side within the reparative zone, rather than the viable side. In the reparative zone, nerve growth factor expression was positively correlated with bone formation parameters derived from micro-computed tomography images. Vascular endothelial growth factor, osteocalcin, CD31(+) vascular endothelial cells, and TUBB3(+) nerve cells also significantly increased in the reparative zone. In conclusion, nerve growth factor expression was consistent across all femoral heads with osteonecrosis and may play a role in reparative reaction to osteonecrotic lesions.

Masquelet's induced membrane technique (MIMT) is a staged surgical procedure that leverages the foreign body induced membrane (IM) that forms around a cement spacer placed into a segmental bone defect to support subsequent bone grafting. The mechanisms by which the IM supports bone consolidation are not fully understood. We present an indirect coculture system for studying IM-MSC interactions using a rat model of MIMT. Compared to control cells, MSC Tnap (alkaline phosphatase) was induced by 4- but not 8-week IM. MSC Spp1 (Osteopontin) was attenuated by both 4- and 8-week IM. Although Tnfrsf11b (osteoprotegrin) in MSC exposed to IM was not different from control cells, it was induced by 8-week IM compared to 4-week IM. MSC Tnfsf11 (RANKL) was reduced by 4-week and 8-week IM. MSC Thbs2 (Tsp2) was induced by 8-week but not 4-week IM. Ablation of macrophages in IM blocked the induction of Thbs2 by 8-week IM. MSC Col1a1 expression was not affected under any condition tested. TMT proteomics analysis of IM-conditioned medium revealed 150 unique secreted proteins, 7 of which were differentially abundant (fold change ≥ 2 and FDR corrected p ≤ 0.05) in 8-week versus 4-week IM secretomes. All differentially abundant proteins were elevated in medium conditioned by 8-week IM. Our data suggest that factor(s) secreted by IM resident cells affect MSC gene expression, and that duration of IM development influences the potency and nature of this paracrine effect. Patient-specific factors including age and interval between MIMT surgeries may affect IM biological potency and graft to bone consolidation.