Bone & Joint Research最新文献

Aims: This review examines the therapeutic potential of adipose tissue-derived stem cell (ADSC) exosomes for osteoarthritis (OA), focusing on their anti-inflammatory and cartilage regeneration properties.

Methods: A PubMed search (2012 to 2024) was conducted using keywords related to ADSCs, exosomes, and OA. Inclusion criteria focused on studies investigating ADSCs and ADSC-exosomes characteristics, animal OA models, and human OA patients. Exclusion criteria included case reports, case series, and conference abstracts.

Results: ADSCs are an abundant stem cell source with low immunogenicity. ADSC-exosomes exhibit anti-inflammatory effects and promote cartilage regeneration via miRNA transport. Preclinical studies demonstrate inhibition of synovial thickening, cartilage destruction, and macrophage activity. Clinical trials suggest that intra-articular ADSCs are safe and effective, with higher doses improving pain relief and cartilage regeneration.

Conclusion: ADSC-exosomes are a promising cell-free therapy for OA, with reduced immune rejection and tumorigenicity compared to ADSC transplantation. Standardizing exosome isolation and production remains a challenge. Further research is needed to confirm long-term safety and efficacy in humans.

Aims: The distal femoral epiphysis and epiphyseal plate are essential for skeletal morphogenesis during development. However, it is unclear how these growth mechanisms are affected by distal femoral torsion (DFT) and patellar instability. This study aimed to investigate how DFT development affects epiphyseal plate growth mechanisms.

Methods: This study evaluated CT-based 3D reconstructed images of the distal femoral epiphyseal plates in 98 knees exhibiting trochlear dysplasia (50 patients). Morphological parameters including femoral anteversion, DFT, and the anatomical epicondylar axis-posterior condylar line (AEA-PCL) angle were measured to determine their relationship with epiphyseal plate development. Finite element modelling was then performed to evaluate how patellar displacement and distal femoral rotation influence epiphyseal stress in juvenile knees. A rat model that had undergone femoral rotational osteotomy was established (n = 12), and trochlear morphology (groove angle and depth) and trabecular microarchitecture (bone volume fraction, thickness, number, and separation) were compared with control specimens by micro-CT analysis at skeletal maturity.

Results: Underdeveloped medial femoral epiphyseal plates were associated with excessive DFT and a large AEA-PCL angle. The medial-to-lateral epiphyseal plate ratio was inversely correlated with DFT and the AEA-PCL angle, suggesting mechanical influences on growth plate morphology. Finite element analysis revealed that medial patellar displacement and femoral external rotation decreased overall epiphyseal stress and shifted its distribution medially. Compared with control specimens, the experimental rats had significantly increased trochlear angles accompanied by reduced trochlear depth and subchondral bone loss in the medial femoral condyles and anterior medial epiphyses.

Conclusion: DFT alters stress distribution across the epiphysis and epiphyseal plate, which modifies the trabecular microarchitecture in both medial femoral condyles and anterior medial epiphyses, and results in different medial-to-lateral ratio of the distal femoral epiphyseal plate which indicates the severity of trochlear dysplasia, although genetic investigations are needed to establish its causality.

Aims: This study examined the effects of surgical alignment techniques and implant design on sagittal plane moments and neuromuscular control during stair navigation in total knee arthroplasty (TKA) patients. We hypothesized that alignment techniques would affect joint biomechanics and neuromuscular control, while implant design would not influence lower limb biomechanics.

Methods: A total of 52 TKA patients were analyzed one year postoperatively, categorized by alignment technique (mechanical alignment (MA) or kinematic alignment (KA)) and implant design (cruciate-retaining fixed bearing (CRFB), medial congruent (MC), and medial stabilized (MS)). Each participant performed five trials of overground walking, then stair ascent and descent at their preferred speed. Sagittal plane lower limb joint moments were calculated using a six-degree-of-freedom model in Visual 3D. Surface electromyography signals were analyzed over the entire gait cycle to assess muscle activation patterns.

Results: The KA alignment group demonstrated greater knee extension moments and a knee-dominant strategy compared with the ankle-dominant strategy in the MA group. Implant design did not affect extension moments, but significantly impacted neuromuscular control. Implants with greater medial anteroposterior (AP) constraint showed lower biceps femoris (BF) activation, while designs with greater AP movement required higher BF activation.

Conclusion: Surgical-alignment techniques, particularly KA, significantly impacted joint biomechanics, promoting a knee-dominant strategy during stair negotiation. Implant design influenced neuromuscular control, with less stable designs requiring higher hamstring activation for stabilization. Those results highlighted the importance of considering both alignment technique and implant design in post-TKA rehabilitation.

Aims: Osteoarthritis (OA) is a chronic joint disorder characterized by progressive cartilage degeneration, inflammation, and subchondral bone remodelling. Herein, the role of exosomes (Exos) extracted from wogonin-pretreated infrapatellar fat pad mesenchymal stem cells (MSCs^IPFP) was explored, and their ability to promote cartilage defect repair in OA was clarified.

Methods: In this study, the therapeutic effects of wogonin on MSCs^IPFP-derived Exos and OA chondrocytes were investigated in vitro, and a mouse OA model was studied in vivo. Human-derived chondrocytes and MSCs^IPFP were isolated and cultured. These cells were characterized through morphological observation, toluidine blue staining, immunofluorescence staining, detection of stem cell surface markers, and induction of directed differentiation. DiI dye was used to label and trace MSCs^IPFP-derived Exo (MSCs^IPFP-Exo). Chondrocyte inflammation and the mouse OA model were induced using interleukin (IL)-1β and destabilization of the medial meniscus (DMM) surgery. To evaluate chondrocyte proliferation and apoptosis, cell counting kit (CCK)-8 assay and flow cytometry were conducted. Articular cartilage destruction in mice was assessed using haematoxylin and eosin (H&E) staining, Safranin O/Fast Green staining, and the Osteoarthritis Research Society International (OARSI) score. Additionally, immunohistochemical staining and/or western blot were performed to examine the expression of Sox9, aggrecan, type II collagen (collagen II), a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5), and matrix metalloproteinase 13 (MMP13).

Results: The isolated chondrocytes could uptake MSC^IPFP-Exo. Wogonin-MSC^IPFP-Exo enhanced chondrocyte proliferation and suppressed apoptosis; Wogonin-MSC^IPFP-Exo significantly alleviated cartilage tissue damage in OA mice compared to untreated controls and MSC^IPFP-Exo-treated OA mice in in vivo experiments. Mechanistically, wogonin-MSC^IPFP-Exo upregulated Sox9, aggrecan, and collagen II protein levels, while downregulating ADAMTS5 and MMP13 protein levels compared to untreated controls and MSC^IPFP-Exo-treated OA mice.

Conclusion: Wogonin pretreatment significantly enhances the ability of MSC^IPFP-Exo to promote cartilage defect repair, and it is expected to be a promising agent for the clinical treatment of OA. Further preclinical and clinical studies are necessary to validate the safety, efficacy, and long-term outcomes of this therapeutic approach before its translation into clinical practice for the treatment of OA.

Aims: Arthroscopic cam resection in femoroacetabular impingement syndrome leads to clinical improvement, but biomechanical studies on the effect of surgical intervention are scarce. In this study, we compared the femoroacetabular contact pressure (CP) in an intact cam morphology and after arthroscopic cam resection. The hypothesis was that arthroscopic cam resection decreases the femoroacetabular CP.

Methods: A cadaveric study was performed on nine hips with a cam morphology (α angle > 60°). CP was assessed using a new hip-specific device and an intracranial pressure (ICP) sensor. These evaluations were performed during hip arthroscopy, in the intact joint and after cam resection, with the joint in different positions. These measurements were normalized and reported as a percentage of the native intact joint.

Results: A statistically significant difference in the mean CP measured with the hip-specific device was observed before and after cam osteoplasty at 0° (41.2% (SD 29.7%); p = 0.014), 30° (54.5% (SD 16.6%); p = 0.011), 60° (39.8% (SD 23.0%); p < 0.001), 80° of flexion (36.3% (SD 22.1%); p < 0.001), and 80° of flexion with 20° of internal rotation (26.0% (SD 22.4%); p < 0.001). The ICP sensor is very fragile and difficult to handle in hip arthroscopy. Consequently, we limited the evaluations using this sensor to five hips. A statistically significant difference in the CP was found before and after cam osteoplasty at 80° of flexion (57.6% (SD 29.1%); p = 0.004).

Conclusion: This biomechanical study evaluated a new hip-specific device to intraoperatively measure the CP in arthroscopic surgery. It showed a significant decrease in the CP after arthroscopic cam resection with the joint in different positions. At 80° of flexion with 20° of internal rotation, a typical position to detect hip impingement, the CP was reduced to 26% after arthroscopic cam resection. The intraoperative measurement of CP provides surgeons with feedback to evaluate the effectiveness of the osteoplasty.

Aims: Arthrofibrosis affects a notable percentage of patients after total knee arthroplasty (TKA). Elevated serum mast cell tryptase (SMCT) levels have been linked to fibrosis, suggesting that SMCT could serve as a biomarker for arthrofibrosis. As such, the aims of this study were to assess SMCT levels in TKA patients, and their possible association with arthrofibrosis and clinical outcomes in a prospective clinical trial.

Methods: We conducted a prospective study involving 219 patients undergoing primary TKA at a single academic medical centre between January 2018 and December 2022. SMCT levels were measured preoperatively, immediately postoperatively, and at six weeks, three months, and one year postoperatively. Secondary outcomes included revision rates, complications, and Knee Society Scores (KSSs). Allergic and inflammatory conditions were assessed for their influence on SMCT levels.

Results: At one year postoperatively, eight patients had developed arthrofibrosis (4%), and three (1.5%) had undergone manipulation under anaesthesia. The mean preoperative SMCT level was 5.6 µg/L (SD 3.4), which decreased significantly to 4.1 µg/L (SD 2.7) immediately postoperatively (p < 0.001). At six weeks the mean SMCT level was 6.4 µg/l (SD 4.1), and was 6.1 µg/l at both three months (SD 4.1) and one year (SD 4.0). Elevated preoperative SMCT levels were not significantly associated with the risk of arthrofibrosis development (OR 3; p = 0.370), nor were immediate postoperative levels (OR 2; p = 0.754) or those at six weeks (OR 1; p = 0.989). Of note, elevated SMCT levels at three months (OR 5; 95% CI 0.4 to 64; p = 0.191) and one year (OR 13; 95% CI 1 to 232; p = 0.077) trended toward an increased risk of arthrofibrosis development, without reaching significance.

Conclusion: In patients undergoing TKA, with the numbers included in this study, there was no significant difference in SMCT levels between patients who did and did not develop arthrofibrosis at any timepoint. However, there was a trend towards elevated SMCT levels at three months and one year in those who developed arthrofibrosis, which merits further study.

Aims: This study uses finite element analysis (FEA) to compare intramedullary nail (IMN) and locking compression plate (LCP) in tibiotalocalcaneal arthrodesis (TTCA), examining biomechanical changes in the joints and assessing which construct better supports arthrodesis under axial loading.

Methods: A 3D finite element model of the foot-ankle complex was constructed from CT images of a 29-year-old male's lower limb. The model included homogeneous cortical and trabecular bones, cartilage, and 29 ligaments. Titanium alloy (Ti6Al4V) implants simulated IMN and LCP fixations. The inferior surfaces of the metatarsals and calcaneus were fixed, and axial loads of 1×, 2×, and 3× body weight (BW) were applied. Von Mises stress and joint displacement evaluated construct stability.

Results: At 1× BW, the IMN model exhibited the highest joint surface stress (32.44 MPa, superior talus) and higher implant stresses than those of the LCP model. Under increased loading, stress rose substantially in both models, peaking at +364.38% in LCP (superior talus) and +130.98% in IMN screws. Stress in the LCP model was more widely distributed across the tibia and calcaneus, while in the IMN model it was concentrated in the talus. At 3× BW, the LCP calcaneus exhibited the largest proportion of elements within the elevated stress range (5.3%). Peak displacement was higher in LCP (376 μm at 1× BW). Although IMN showed larger relative displacement increases, absolute joint displacements remained consistently lower than LCP.

Conclusion: Both IMN and LCP provide sufficient mechanical support for TTCA. IMN offers greater initial stability, reflected by lower joint displacement, but generates higher implant stress, particularly under increased loading. In contrast, LCP exhibits more uniform stress distribution and smaller screw stress increases as load rises, and may offer improved mitigation of implant stress concentrations under elevated loads.

Aims: Bone destruction is a pivotal pathological factor in the development of joint disability in rheumatoid arthritis (RA) patients, and there is a paucity of safe and effective drugs targeting bone destruction. Xuetong (Kadsura heteroclita Roxb), a traditional Tujia medicine with blood-activating and pain-relieving properties, has been used for the treatment of RA. Xuetongsu, as the primary anti-RA active component, has demonstrated inhibitory effects on joint inflammation and swelling in arthritic rats, as well as the potential to prevent bone destruction. However, the precise mechanisms by which these effects occur remain to be elucidated. This study aims to explore the potential action targets and mechanisms of Xuetongsu in RA-induced bone destruction.

Methods: RA bone destruction is closely related to the activation of the RANKL/RANK/NFATc1 pathway. In this study, databases such as TDD were used for KEGG and GO enrichment analyses to identify the potential targets of Xuetongsu in regulating the RANKL/RANK/NFATc1 pathway for anti-RA bone destruction. Molecular docking was employed to evaluate the binding affinity and interaction sites between Xuetongsu and RANKL. For in vitro experiments, a RANKL-induced osteoclastogenesis model using RAW264.7 cells was established to assess Xuetongsu's effects on osteoclastogenesis and bone resorption capacity. In vivo, a stable adjuvant-induced arthritis rat model was developed to investigate the anti-bone destruction effects of oral Xuetongsu and systematically explore its underlying mechanisms.

Results: Based on the findings from both in vitro and in vivo experimental models, it was revealed that Xuetongsu can directly target RANKL and inhibit the activation of the RANKL/RANK/NFATc1 pathway, thereby suppressing osteoclast-mediated bone resorption and preventing osteoclastogenesis.

Conclusion: These findings indicate that Xuetongsu has been demonstrated to inhibit bone destruction by targeting the RANKL/RANK/NFATc1 pathway and could serve as a potential therapeutic agent for RA-associated bone destruction.

Aims: To investigate the spatial distribution of structural features at the anterior cruciate ligament (ACL)-bone interface and examine their relationship with local tensile properties and stress distribution, thereby elucidating the structure-function relationship at this critical soft-hard tissue junction.

Methods: High-resolution micro-CT was employed to obtain 3D imaging of 17 porcine ACL-femur interface specimens. Structural features were analyzed across different functional regions, specifically comparing the anteromedial (AM) and posterolateral (PL) bundles, as well as the direct and indirect insertion sites. Parameters assessed included macroscopic area, cortical tissue thickness, fibre angle, bone volume fraction (BVF), and degree of anisotropy (DA) in trabecular bone. Additionally, tensile tests were conducted on six porcine specimens to determine the elastic moduli of different interface regions. Finite element analysis was conducted to investigate stress distribution across the ACL-femur interface during the gait cycle. Spatial variations in structural features were then compared with local tensile properties and stress levels to elucidate the structure-function relationship.

Results: Significant differences in structural features, tensile moduli, and peak stress were observed among the functional regions of the ACL-femur interface. The spatial distribution of structural features closely mirrored the patterns of mechanical properties and stress. Regions exhibiting higher tensile moduli and experiencing greater peak stress demonstrated increased cortical tissue thickness and BVF (indirect > direct). Furthermore, regions with larger fibre angles showed higher trabecular DA (PL > AM; direct > indirect). Overall, the differences between the direct and indirect regions were more pronounced than those between the AM and PL bundles.

Conclusion: The mechanical function of the ACL-bone interface is strongly associated with the spatial organization of its structural features. The indirect region differs significantly from the direct region in both structural and mechanical characteristics, highlighting region-specific adaptations for load transfer at the ligament-bone junction.

Aims: The Oxford Knee Score (OKS) is a 12-item patient-reported outcome measure (PROM), developed for patients who are candidates for total knee arthroplasty (TKA). A prerequisite for a PROM to be considered an adequate measurement instrument is a unidimensional structure as demonstrated by a modern test theory (MTT) model, meaning that each (sub)scale reflects one construct (e.g. pain). However, the structural validity of OKS has only been sparsely evaluated with MTT, and with ambiguous results. This study aimed to assess the structural validity of the Danish OKS. Since the OKS includes items addressing both pain and physical function, it was hypothesized that scores were more accurately reported as two separate subscales.

Methods: OKS responses from a study of 1,059 patients treated with a TKA were obtained. Four random subsamples (each with 400 patients) - female and male, preoperative and three months postoperative - were assessed by confirmatory factor analysis (CFA) and Rasch analysis. CFA model fit was evaluated using the chi-squared statistic and indices of close fit. Rasch fit was evaluated with item fit statistics. Both a one-factor solution and two-factor solutions with scores based on two separate subscales were considered for each subsample.

Results: OKS data did not fit the original unidimensional model of one total score. Reporting OKS data as the two subscales "pain" and "function" improved CFA fit, but model fit was still inadequate. Results were consistent across subsamples.

Conclusion: The structural validity of the Danish OKS is inadequate for evaluating patients awaiting TKA or surgically treated with TKA. OKS data should therefore be interpreted with caution. Randomized treatment studies showing no difference in OKS scores may be reanalyzed based on the two domains to reduce the risk of a potential type-2 error.