Joint Osteoarthritis Research Articles

The relationship of IL-1β/IL-10 ratio, pain degree and CTX-II levels with histopathological features of facet joint osteoarthritis in patients with lumbal spinal canal stenosis

Introduction: Osteoarthritis of the facet joint is the final stage of spinal degeneration. Cytokines are believed to play a crucial role in degenerative joint diseases. This study was conducted to prove the relationship between the IL-1β/IL-10 ratio, the degree of pain, and the levels of CTX-II with the histopathological features of facet joint osteoarthritis in patients with lumbar spinal canal stenosis. Methods: The research design is a Cross-Sectional design with consecutive sampling. This study involves patients diagnosed with lumbar spinal canal stenosis according to the hospital's standard operating procedure from January 2023 to September 2023. CTX-II and Plasma IL-10 cytokine levels were examined using the Enzyme-Linked Immunosorbent Assay (ELISA) method. Histopathology is obtained through staining under a microscope. The data obtained in the study were analyzed, and significant result was p<0.05. Results: A total of 38 samples were obtained. There were more males than females, with 52.6% and 47.4%, respectively. The demographic data showed an average age of 58 years. A statistically significant relationship was found between CTX-II and the histological degree of OA in facet joints, with a p-value of 0.043 (p < 0.05) and a weak positive correlation strength (0.330). Meanwhile, the IL-1β/IL-10 ratio showed a weak positive correlation (0.490) with a p-value of 0.002. ODI exhibited a positive correlation with a strength of (0.393) and a p-value of 0.015. A statistically significant relationship was found for IL-1β with a p-value of 0.039, and IL-10 with a p-value of 0.031 (p > 0.05). The correlation strengths were positive for IL-1β (0.327) and negative for IL-10 (-0.336). Conclusion: There was a relationship between the IL-1β/IL-10 ratio, the degree of pain, and the levels of CTX-II with the histopathological features of facet joint osteoarthritis in patients with lumbar spinal canal stenosis.

Simultaneously Modulating HIF-1α and HIF-2α and Optimizing Macrophage Polarization through the Biomimetic Gene Vector toward the Treatment of Osteoarthritis.

In osteoarthritis (OA), articular cartilage is continuously submerged in a hypoxic environment throughout life, and hypoxia-inducible factors (HIFs) play a crucial role in OA progression. Among the various HIF phenotypes, HIF-1α positively contributes to maintaining the stability of the articular cartilage matrix. In contrast, HIF-2α has a detrimental effect, leading to chondrocyte apoptosis and exacerbating inflammation. Notably, there is currently no simultaneous regulation of HIF-1α and HIF-2α for OA treatment. Thus, the biomimetic gene vector (MENP) was developed for co-delivery of siHIF-2α and Mg2+ to the inflamed regions in OA joints, comprising an inner core consisting of siHIF-2α and Mg2+ and an outer M2 macrophage membrane. Invitro and invivo studies demonstrate that MENP effectively targets inflamed areas, efficiently silences HIF-2α, and facilitates HIF-1α-mediated cartilage restoration through Mg2+. Furthermore, it indirectly promotes the polarization of macrophages toward an anti-inflammatory M2 phenotype through its action on inflamed synoviocytes. Overall, MENP is an efficient biomimetic vehicle for alleviating inflammation and promoting cartilage repair, representing an appealing approach for OA treatment.

Greater than recommended stiffness and power setting of a stance-phase powered leg prosthesis can improve step-to-step transition work and effective foot length ratio during walking in people with transtibial amputation.

People with unilateral transtibial amputation (TTA) using a passive-elastic prosthesis exhibit lower positive affected leg trailing work (ALtrail Wpos) and a greater magnitude of negative unaffected leg leading work (ULlead Wneg) during walking than non-amputees, which may increase joint pain and osteoarthritis risk in the unaffected leg. People with TTA using a stance-phase powered prosthesis (e.g., BiOM, Ottobock, Duderstadt, Germany) walk with increased ALtrail Wpos and potentially decreased magnitude of ULlead Wneg compared to a passive-elastic prosthesis. The BiOM includes a passive-elastic prosthesis with a manufacturer-recommended stiffness category and can be tuned to different power settings, which may change ALtrail Wpos, ULlead Wneg, and the prosthesis effective foot length ratio (EFLR). Thirteen people with TTA walked using 16 different prosthetic stiffness category and power settings on a level treadmill at 0.75-1.75m/s. We constructed linear mixed effects models to determine the effects of stiffness category and power settings on ALtrail Wpos, ULlead Wneg, and EFLR and hypothesized that decreased stiffness and increased power would increase ALtrail Wpos, not change and decrease ULlead Wneg magnitude, and decrease and not change prosthesis EFLR, respectively. We found there was no significant effect of stiffness category on ALtrail Wpos but increased stiffness reduced ULlead Wneg magnitude, perhaps due to a 0.02 increase in prosthesis EFLR compared to the least stiff category. Furthermore, we found that use of the BiOM with 10% and 20% greater than recommended power increased ALtrail Wpos and decreased ULlead Wneg magnitude at 0.75-1.00m/s. However, prosthetic power setting depended on walking speed so that use of the BiOM increased ULlead Wneg magnitude at 1.50-1.75m/s compared to a passive-elastic prosthesis. Ultimately, our results suggest that at 0.75-1.00m/s, prosthetists should utilize the BiOM attached to a passive-elastic prosthesis with an increased stiffness category and power settings up to 20% greater than recommended based on biological ankle values. This prosthetic configuration can allow people with unilateral transtibial amputation to increase ALtrail Wpos and minimize ULlead Wneg magnitude, which could reduce joint pain and osteoarthritis risk in the unaffected leg and potentially lower the metabolic cost of walking.

Clinical Outcomes of Modified Suture Buttons for Tibial Side Fixation in Anterior Cruciate Ligament Reconstruction: A Retrospective Comparative Study.

Introduction Restoring knee joint stability and resuming sports activities are important objectives of anterior cruciate ligament (ACL) reconstruction. The maintenance of anterior knee stability after ACL reconstruction is contingent on graft tension. Various devices and techniques have been used to achieve robust tibial graft tendon fixation, and their advantages and disadvantages are established. However, a gold standard has not been established. Therefore, we aimed to determine whether anterior knee joint stability and clinical outcomes of graft tendon fixation could be improved using a recently modified suture button (MSB) compared with using an adjustable suspensory fixator (ASF) at 1 year after double-bundle ACL reconstruction. Methods This study retrospectively analyzed postoperative data derived from 79 patients at a single center between January 2016 and December 2021. The patients were assigned to groups that underwent double-bundle ACL reconstruction with tibial fixation using an MSB (n = 30) that maintains tension while tying sutures, or an ASF (n = 49). We then compared complications, clinical outcomes and knee joint stability at 1 year postoperatively. Rates of postoperative infection, graft rupture, implant removal and residual anterior knee laxity (AKL) were compared between the groups using chi-square tests. Patient-reported outcome measures (PROM) based on Forgot Joint Score-12, Knee Injury and Osteoarthritis Outcome, and Lysholm Knee scoreswere compared using Mann-Whitney U tests. Results One patient in the MSB group developed postoperative infection. Rates of graft rupture and implant removal in the MSB and ASF groups were 3.3% and 4.1%, and 3.6% and 10.2%, respectively. None of the PROMs differed between the groups. The proportions of postoperative AKL were 3.6% and 14.9% in the MSB and ASF groups, respectively. A trend towards lower postoperative AKL in the MSB group did not reach statistical significance (p = 0.25). Conclusions The incidence of AKL at a year after ACL reconstruction using the MSB was 3%. Postoperative AKL and clinical outcomes were comparable between the MSB and ASF groups. A low AKL rate and positive postoperative outcomes indicated that MSB could be an option for tibial-side fixation in ACL reconstruction.

Therapeutic Effects of Mesenchymal Stem Cells Derived from Bone Marrow and Adipose Tissue in a Rat Model of Temporomandibular Osteoarthritis

ObjectivesTo examine the potential of intra-articular administration of mesenchymal stem cells (MSCs) derived from bone marrow or adipose tissue to mitigate synovial inflammation in a rat model of temporomandibular joint (TMJ) osteoarthritis (OA). MethodsIn this experimental study, 40 rats were divided into 4 groups: (1) Control group; (2) Untreated TMJ-OA group; (3) TMJ-OA group treated with bone marrow-derived MSCs; (4) TMJ-OA group treated with adipose tissue-derived MSCs. The TMJ-OA model was established by inducing synovial inflammation through the intra-articular administration of complete Freund’s adjuvant (CFA). After 8 weeks of TMJ-OA establishment, the animals were sacrificed and each mandibular condyle was extracted for histological evaluation. ResultsThe untreated TMJ-OA group had significantly higher synovial inflammation, as indicated microscopically by higher grades of synovial membrane hyperplasia and adhesion, vascular vasodilation, and fibrin deposition than the control group (p < 0.001). Both TMJ-OA groups treated with MSCs had lower grades of synovial inflammation and less severe synovitis than the untreated TMJ-OA group (p < 0.001). The TMJ-OA group treated with adipose tissue-derived MSCs showed lower grades of synovial membrane hyperplasia and higher grades of fibrin deposition than the that treated with bone marrow-derived MSCs (p < 0.001). Other indicators of synovial inflammation and synovitis severity were comparable between the two treatment groups. ConclusionsAdministration of CFA to the TMJ-OA rat model augmented synovial inflammation. Intra-articular administration of MSCs derived from either bone marrow or adipose tissue attenuated the microscopic manifestations of this inflammation, indicating the therapeutic potential of this treatment for TMJ-OA.

Osteocyte-derived exosomes regulate the DLX2/wnt pathway to alleviate osteoarthritis by mediating cartilage repair

Background Chondrocyte viability, apoptosis, and migration are closely related to cartilage injury in osteoarthritis (OA) joints. Exosomes are identified as potential therapeutic agents for OA. Objective This study aimed to investigate the role of exosomes derived from osteocytes in OA, particularly focusing on their effects on cartilage repair and molecular mechanisms. Methods An injury cell model was established by treating chondrocytes with IL-1β. Cartilage repair was evaluated using cell counting kit-8, flow cytometry, scratch test, and Western Blot. Molecular mechanisms were analyzed using quantitative real-time PCR, bioinformatic analysis, and Western Blot. An OA mouse model was established to explore the role of exosomal DLX2 in vivo. Results Osteocyte-released exosomes promoted cell viability and migration, and inhibited apoptosis and extracellular matrix (ECM) deposition. Moreover, exosomes upregulated DLX2 expression, and knockdown of DLX2 activated the Wnt pathway. Additionally, exosomes attenuated OA in mice by transmitting DLX2. Conclusion Osteocyte-derived exosomal DLX2 alleviated IL-1β-induced cartilage repair and inactivated the Wnt pathway, thereby alleviating OA progression. The findings suggested that osteocyte-derived exosomes may hold promise as a treatment for OA.

Poster 208: Predicting Patient-Specific Hip Motion During Functional Activities After Periacetabular Osteotomy

Objectives: Developmental dysplasia of the hip (DDH) is a condition in which the hypoplastic acetabulum provides inadequate coverage of the femoral head. This abnormal coverage, while pathological, may be advantageous in some sporting and recreational activities needing significant hip range of motion (ROM), including dance, ballet, and performing arts. Although DDH allows patients to perform activities requiring supraphysiologic hip motion, subluxation of the hip joint generates excessive articular stresses, leading ultimately to pain, osteoarthritis (OA), and total joint arthroplasty. In some DDH patients, this degenerative pathway can be interrupted by performing a periacetabular osteotomy (PAO) to reorient the acetabular fragment, which increases femoral head coverage and reduces intra-articular stresses. This improved coverage is believed to come at the sacrifice of range of motion, particularly noticed while performing high-demand activities requiring supraphysiologic end-range motion. This study addresses the questions: 1. Does a PAO reduce the range of motion of the hip enough to reduce a patient’s ability to perform daily living, recreational and sporting activities? 2. If so, what activities are most impacted by these changes? Methods: We created an inventory of daily living, recreational and sporting activities commonly performed by patients with hip dysplasia. A systematic review of the literature provided the maximum hip range of motion required (required ROM) to perform eight activities of daily living (ADL) and thirteen sporting movements. The concurrent peak value for each anatomic component of hip motion, (i.e flexion/extension; adduction/abduction; internal/external rotation) was classified for every activity in terms of physiologic demand relative to the average ROM of the adult hip. Based on these values, we created a 7-level ordinal scale according to the peak kinematic demand required to perform each activity (Table 1), ranging from low to extreme difficulty. To examine the impact of a PAO on the limits of hip motion, we selected, with IRB approval, a cohort of 24 dysplastic hips (12 left and 12 right). Patient-specific 3D models of each pelvis and hip joint were created from preoperative CT scans, and each activity in our hip inventory was simulated using a custom Matlab hip simulation routine. For each activity, the ROM of the hip was recorded as the point at which either bony impingement was detected, or the specified movement was successfully completed. The percentage of the required motion successfully completed (percent function) was then calculated (100*measured ROM/required ROM) for each movement. This procedure was repeated on the same hips after completion of a computer-simulated PAO according to the technique described by Ganz and colleagues in which the LCEA was increased to 35° and reoriented anteriorly to appropriately restore head coverage. Wilcoxon Signed Rank tests were performed to compare preoperative and postoperative percent function for each movement. Results: When all activities were combined, there was no significant difference (p &gt; 0.05) between preoperative function (99.2 ± 0.6%) and postoperative function (98.0 ± 1.1%). The flexion portions of the right and left grand écart latéral, commonly used ballet movements, were the only activities where percent function was significantly decreased after PAO. Before surgery, the left hips performed 96.8 ± 1.8% of the motion required for the left grand écart latéral whereas after surgery hip function decreased to 82.5 ± 7.6% (p &lt; 0.05). Preoperatively, the right hips performed the right grand écart latéral at 96.7 ± 3.3% compared to 77.4 ± 8.3% postoperatively (p &lt; 0.05). There were no significant differences between preoperative and postoperative function for any other activities within the hip inventory. Conclusions: After testing a broad range of movements found in both daily life and sporting and recreational activities, just two of the twenty-one activities were significantly impaired after a computer-simulated PAO. A lack of significant change in percent function for most movements between preoperative and postoperative hips indicates that even high performing patients who undergo a PAO can expect little to no change in their ability to perform many of the activities they enjoyed before surgery. A significant change, however, was seen in the ballet positions right and left grand écart latéral and patients requiring performance of these activities after PAO should be counseled preoperatively regarding the demands of their sporting and recreational activities and their postoperative expectations. [Figure: see text]

Clinical Applicability of Autologous Chondrocyte Implantation for the Treatment of Osteochondral Defects: A Meta-analysis.

Osteoarthritis and other joint disorders are the leading cause of disability in the elderly and the treatment of joint lesions is challenging. Autologous chondrocyte implantation (ACI) has been reported with variable effects for the treatment of osteochondral and other joint lesions. In this study, we performed a meta-analysis of the recent literature to determine the clinical applicability of ACI for osteochondral defects. A meta-analysis was performed on the recent literature showing the effects of ACI on osteochondral defects. The PUBMED, ScienceDirect and Google Scholar databases were used to identify eligible studies from Jan 2010 to Sep 2022. Both fixed and random models of meta-analysis were applied with all reported scoring systems to quantify the effectiveness of ACI on osteochondral defects. The pool data of 965 patients as a case series after ACI from a fixed model showed a significant improvement in the osteochondral defects (odds ratio = 8.75, 95%CI = 7.127 to 10.743, p = 0.000). These results were further verified by a random model of meta-analysis. The data also showed a substantial heterogeneity among the studies used in the meta-analysis (Q-value = 160.41, I-squared = 87.53, p = 0.000). Furthermore, this meta-analysis also compared different ACI procedures with different scoring systems but the overall outcome remains the same as ACI was found to be useful for the healing of the osteochondral defects. This meta-analysis of 965 case series revealed that the ACI markedly improved the damage osteochondral defects scores but the optimal treatment is still controversial, therefore further studies are needed to validate these findings in a clinical setting.

Effect of Retro Walking Versus Balance Training on Pain and Functional Disability of Geriatric Patients with Knee Joint Osteoarthritis: Randomized Controlled Trail

Effect of Retro Walking Versus Balance Training on Pain and Functional Disability of Geriatric Patients with Knee Joint Osteoarthritis: Randomized Controlled Trail

Seven-Year Longitudinal Study: Clinical Evaluation of Knee Osteoarthritic Patients Treated with Mesenchymal Stem Cells.

Background/Objectives: Numerous studies have demonstrated the safety and efficacy of intraarticular stem cell injections for treating osteoarthritic knee joints, reporting symptom reduction and pain relief within a few months of treatment. Here, we report the results of a 7-year follow-up after a single intraarticular injection of 0.5-1 × 107 autologous adipose tissue-derived mesenchymal stem cells in patients with OA (Kellgren-Lawrence grade 2 to 4). Methods: Nine patients were treated, and two patients had bilateral disease. Patients were evaluated clinically and radiologically using X-ray and MRI. A comprehensive statistical analysis was undertaken to evaluate the obtained results. Results: All clinical scores and range of motion significantly improved within the first six months after injection. At the 18-month time point, a significant improvement in cartilage structure was observed on MRI while X-ray showed no changes in subchondral bone of distal femur and proximal tibia. At the 60-month time point, the clinical scores were still improved compared to baseline, except for the range of motion, which decreased almost back to the baseline level. At 84 months, the clinical scores decreased significantly toward the baseline level, but the MRI structural characteristics of cartilage still remained significantly better than those measured at baseline. Conclusions: Adipose tissue-derived stem cell therapy has substantial long-term clinical effects on patients with knee osteoarthritis.

Effects of overweight and obesity on lower limb walking characteristics from joint kinematics to muscle activations

BackgroundObesity is a crucial factor that increases the risk of initiating and advancing knee osteoarthritis. However, it remains unclear how obesity directly impacts the biomechanical experience of the lower limb joints, potentially triggering or exacerbating joint degeneration. This study investigated the interactive effects of BMI augmentation on lower limb kinematics, kinetics, and muscle activations during walking. MethodologyA group of 60 participants underwent a three-dimensional gait analysis. These individuals were categorized into three groups based on their body mass index (BMI): those with a BMI below 25 were classified as having a healthy weight, those with a BMI between 25 and 30 were categorized as overweight, and those with a BMI exceeding 30 were considered obese. This study analyzed the gait of 60 participants categorized by BMI. During walking trials, they recorded ground reaction forces electromyography of leg muscles like the gastrocnemii, hamstrings, and quadriceps. Lower limb joint angles and net moments were also calculated. Statistical mapping identified variations in kinematic, kinetic, and muscle activation patterns across the stance phase between BMI groups. ResultsThe results displayed distinct biomechanical patterns in obese individuals. Notably, there was a significant increase in flexion observed in the hip and knee joints (P < 0.001) during the initial stance phase and an increase in hip and knee adduction angles and moments throughout the entire stance phase (P < 0.001). Additionally, muscle activations underwent significant changes (P < 0.01), with a positive correlation noted with the BMI factor. This correlation was most pronounced during the early stance phase for the quadriceps and hamstring muscles and the late stance phase for the gastrocnemius. ConclusionThese findings represent a comprehensive picture that contributes to understanding how excess weight and obesity influence joint biomechanics, highlighting the associated risk of joint osteoarthritis.

Decrease in pelvic incidence after adult spinal deformity surgery is a predictive factor for progression of hip joint osteoarthritis

BackgroundThis study aimed to evaluate the association between spinopelvic alignment parameters and hip osteoarthritis progression after spinal alignment correction surgery for adult spinal deformity, focusing on the preoperative to postoperative change in spinopelvic alignment.MethodsThis retrospective study enrolled 100 adult spinal deformity patients (196 hip joints) who underwent spinal fusion surgery, after excluding four joints with previous total hip arthroplasty. Acetabular roof obliquity (ARO), center edge angle (CE) and Kellgren and Lawrence (KL) grade were measured in the hip joint. Spinopelvic alignment parameters were measured preoperatively and 1-month postoperatively and the changes (Δ) during this period were calculated. Patients were followed-up for ≥ 5 years and factors associated with KL grade progression at 5-years postoperatively were determined by logistic regression analysis.ResultsIn the analysis with all cases, KL grade progressed in 23 joints. Logistic regression analysis revealed age (OR: 1.098, 95% CI: 1.007–1.198, p = 0.019), ARO (OR: 1.176, 95% CI: 1.01–1.37, p = 0.026), and Δ PI (OR: 0.791, 95% CI: 0.688–0.997, p < 0.001) as parameters significantly associated with KL grade progression. On the other hand, in the analysis limited to 185 cases with 1-month postoperative KL grade of 0, KL grade progressed in 13 joints. Logistic regression analysis revealed PI-LL (OR: 1.058, 95% CI: 1.001–1.117, p = 0.04), ΔPI (OR: 0.785, 95% CI: 0.649–0.951, p < 0.001), and ΔCobb (OR: 1.127, 95% CI: 1.012–1.253, p = 0.009) as parameters significantly associated with progression.ConclusionsBoth the overall and limited analyzes of this study identified preoperative to postoperative change in PI as parameters affecting the hip osteoarthritis progression after spinal fusion surgery. Decrease in PI might represent preexisting sacroiliac joint laxity. Patients with this risk factor should be carefully followed for possible hip osteoarthritis progression.

Primed IFN-γ-Umbilical Cord Stem Cells Ameliorate Temporomandibular Joint Osteoarthritis.

Temporomandibular joint osteoarthritis (TMJOA) is a degenerative disorder affecting the temporomandibular joint (TMJ), marked by persistent inflammation and structural damage to the joint. Only symptomatic treatment is available for managing TMJOA. Human umbilical cord mesenchymal stem cells (hUC-MSCs) show potential for treating TMJOA via their immune-modulating actions in the disease area. In addition, stimulation of inflammatory cytokines such as interferon-gamma in hUC-MSCs improves the therapeutic activity of naïve stem cells. Emerging evidence indicates that macrophages play significant roles in regulating joint inflammation through diverse secreted mediators in the pathogenesis of TMJOA. This study was conducted to evaluate the effects of inflammatory cytokine-stimulated hUC-MSCs in repairing TMJOA-induced cartilage lesions and the role of macrophages in the disease. Our in vitro data showed that stimulated hUC-MSCs induce M2 polarization of macrophages and enhance the expression of anti-inflammatory molecules. These effects were subsequently validated invivo. In a rat model of TMJOA, stimulated hUC-MSCs ameliorated inflammation and increased M2 macrophages ratio. Our results indicate that hUC-MSCs stimulated by inflammatory cytokines modulate the activation of M2 macrophages, thereby shifting the local osteoarthritis microenvironment toward a prochondrogenic state and facilitating cartilage repair in inflammatory conditions. Stimulating hUC-MSCs with inflammatory cytokines could potentially offer an effective therapeutic approach for TMJOA, with macrophages playing a pivotal role in immune modulation.

Bioinspired nanozyme-reinforced hydrogels with free radical scavenging capability for treating temporomandibular joint osteoarthritis

Temporomandibular joint osteoarthritis (TMJ-OA) is usually caused by increased friction at the joint interface, excessive release of inflammatory factors and catabolic enzymes, and free radical accumulation, which can lead to accelerated degradation and damage of cartilage. In this study, we develop a biological metabolism-inspired injectable hydrogel crosslinking by hydrazide modified hyaluronic acid (HA-HYD), aldehyde modified hyaluronic acid (HA-ALD), and ε-polylysine coated catalase-mimic nanozyme (mesoporous manganese cobalt oxide). Herein, this nanozyme-reinforced hydrogel with outstanding and durable reactive oxygen species (ROS) depletion capability and biocompatibility can alleviate the oxidative stress microenvironment, improve cell viability and proliferation, as well as up-regulate chondrogenic related gene expression and cartilage matrix formation of chondrocytes in vitro. Intra-articular administration of this engineered hydrogel can effectively scavenge endogenous over-expressed ROS to ameliorate the harsh microenvironment in the cavity of TMJ-OA. The nanozyme-reinforced hydrogel reduced proinflammatory cytokines (TNF-α, IL-1β, and IL-6) and enhance anti-inflammatory cytokines (IL-10) expression, induced polarization of synovial macrophages towards M2 phenotype, alleviated structural damage to the cartilage and subchondral bone of the condyle, thus reducing cartilage matrix destruction and protect cartilage in osteoarthritis. In summary, the bioinspired nanozyme-reinforced hydrogels might be used as a promising ROS scavenger for treatment of TMJ-OA.

Early changes in asporin levels in osteoarthritis of the temporomandibular joint

ObjectivesThe present study aimed to elucidate the pathogenesis of temporomandibular joint (TMJ) osteoarthritis (TMJ-OA) in a mouse model. We investigated morphological and histological changes in the head of mandible cartilage and early immunohistochemical (IHC) changes in transforming growth factor (TGF)-β, phosphorylated Smad-2/3 (p-Smad2/3), a TGF-β signaling molecule, and asporin. MethodsTMJ-OA was induced in a mouse model through unilateral partial discectomy. Micro-computed tomography (micro-CT) and safranin-O staining were performed to morphologically and histologically evaluate the degeneration of the head of mandible caused by TMJ-OA. IHC staining for TGF-β, p-Smad2/3, and asporin was performed to evaluate the changes in protein expression. ResultsIn the experimental group, three-dimensional (3D) morphometry revealed an enlarged head of mandible and safranin-O staining showed degeneration of cartilage tissue in the early stages of TMJ-OA compared to the control group. IHC staining revealed that TGF-β, p-Smad2/3, and asporin expression increased in the head of mandible cartilage before the degeneration of cartilage tissue, and subsequently decreased for a short period. ConclusionThe findings suggested a negative feedback relationship between the expression of asporin and the TGF-β/Smad transduction pathway, which may be involved in the degeneration of the head of mandible in the early stages of TMJ-OA. Asporin is a potential biomarker of the early stages of TMJ-OA, which ultimately leads to the irreversible degeneration of TMJ tissues.

MAÏA Trapeziometacarpal Joint Arthroplasty: Clinical and Radiological Outcomes of 76 Patients With More Than 10 Years of Follow-Up

Trapeziometacarpal (TMC) joint replacement has become a valid option in the therapeutic arsenal of TMC joint osteoarthritis in Europe. Good mid-term results of the MAÏA TMC joint prosthesis suggested that it is a reliable procedure. This study aimed to assess the long-term results of this modular uncemented ball-and-socket hydroxyapatite-coated implant. This single-center retrospective study evaluated 92 MAÏA TMC joint prostheses in 76 patients with a minimum of 10 years of follow-up. Indications for the procedure were painful TMC joint osteoarthritis both at rest and during activity, despite nonsurgical treatment for more than six months. Pre- and postoperative clinical and radiographic outcomes were compared. Mean follow-up was 134 months (range: 120-158 months). Mean age at the time of surgery was 67 years (range: 53-84 years). The cohort comprised 86.8% of women (n= 66). The mean Quick Disabilities of the Arm, Shoulder, and Hand score improved from 61.3 ± 17.1 to 19.6 ± 16. Range of motion was restored, and postoperative mobility was comparable with that of the contralateral side. Final Kapandji opposition score was almost normal (9.2 ± 0.7). Final key pinch and grip strength improved by 26% and 39%, respectively. Eight implants were surgically revised, six for trapezium cup loosening and two for instability because of polyethylene wear. Three cases of traumatic fracture of the trapezium in older patients were successfully treated with a cast for eight weeks. Five of 26 (20.8%) cases of preoperative-reducible z-deformity were not totally corrected after surgery. The Kaplan-Meier survival over 10 years was 88% (95% confidence interval: 84-93) versus 93% (95% confidence interval: 87-98) over 5 years. MAÏA TMC joint prosthesis is a reliable long-term surgical procedure for TMC joint osteoarthritis, improving overall function beyond 10 years. Therapeutic IV.

Cross-species transcriptomics identifies obesity associated genes between human and mouse studies

BackgroundFundamentally defined by an imbalance in energy consumption and energy expenditure, obesity is a significant risk factor of several musculoskeletal conditions including osteoarthritis (OA). High-fat diets and sedentary lifestyle leads to increased adiposity resulting in systemic inflammation due to the endocrine properties of adipose tissue producing inflammatory cytokines and adipokines. We previously showed serum levels of specific adipokines are associated with biomarkers of bone remodelling and cartilage volume loss in knee OA patients. Whilst more recently we find the metabolic consequence of obesity drives the enrichment of pro-inflammatory fibroblast subsets within joint synovial tissues in obese individuals compared to those of BMI defined ‘health weight’. As such this present study identifies obesity-associated genes in OA joint tissues which are conserved across species and conditions.MethodsThe study utilised 6 publicly available bulk and single-cell transcriptomic datasets from human and mice studies downloaded from Gene Expression Omnibus (GEO). Machine learning models were employed to model and statistically test datasets for conserved gene expression profiles. Identified genes were validated in OA tissues from obese and healthy weight individuals using quantitative PCR method (N = 38). Obese and healthy-weight patients were categorised by BMI > 30 and BMI between 18 and 24.9 respectively. Informed consent was obtained from all study participants who were scheduled to undergo elective arthroplasty.ResultsPrincipal component analysis (PCA) was used to investigate the variations between classes of mouse and human data which confirmed variation between obese and healthy populations. Differential gene expression analysis filtered on adjusted p-values of p < 0.05, identified differentially expressed genes (DEGs) in mouse and human datasets. DEGs were analysed further using area under curve (AUC) which identified 12 genes. Pathway enrichment analysis suggests these genes were involved in the biosynthesis and elongation of fatty acids and the transport, oxidation, and catabolic processing of lipids. qPCR validation found the majority of genes showed a tendency to be upregulated in joint tissues from obese participants. Three validated genes, IGFBP2 (p = 0.0363), DOK6 (0.0451) and CASP1 (0.0412) were found to be significantly different in obese joint tissues compared to lean-weight joint tissues.ConclusionsThe present study has employed machine learning models across several published obesity datasets to identify obesity-associated genes which are validated in joint tissues from OA. These results suggest obesity-associated genes are conserved across conditions and may be fundamental in accelerating disease in obese individuals. Whilst further validations and additional conditions remain to be tested in this model, identifying obesity-associated genes in this way may serve as a global aid for patient stratification giving rise to the potential of targeted therapeutic interventions in such patient subpopulations.

Клинико-экономический анализ эффективности использования индивидуальных и серийных имплантатов при эндопротезировании тазобедренного и коленного суставов.

One of the pressing issues of modern medicine is the need to improve the results of surgical treatment of patients with stage III osteoarthritis of large joints (according to the classification of N. S. Kosinskaya), as well as with loosening of the components of hip and knee joints through the use of techniques that have high clinical and economic efficiency and including the use of computer modeling and additive 3D printing technologies. Purpose of the study: to conduct a clinical and economic analysis of the effectiveness of using individual and serial components of endoprostheses in the surgical treatment of patients with stage III hip osteoarthritis (according to N. S. Kosinskaya’s classification), as well as with loosening of hip and knee joint implants. Methods: clinical-radiological, computed tomographic, biomechanical, statistical, analytical, sociological. The study included 348 patients who were divided into 10 groups depending on the individual and serial components of implants used in their treatment. Results. The effectiveness of surgical treatment of stage III hip osteoarthritis using individual acetabular implants in primary hip replacement, assessed using QALYs, was 0.79, and the CER (“cost-effectiveness”) indicator was 350,424.7. Moreover, the use of only serial imlants in a similar operation led to a decrease in CER to 262,977.2 and QALY to 0.63. Higher QALYs have also been observed with the use of additive technologies in revision hip arthroplasty. The effectiveness of surgical treatment using individual implants for type IIIa acetabular defect was 0.77 (CER – 341,110), for type IIIb – 0.6 (CER – 496,754.3). When using serial components of a revision hip joint implants for type IIIa acetabular defect, the QALY was 0.4 (CER – 540,462.5), for type IIIb – 0.4 (CER – 653,500.5). The best QALYs (0.15) and CER (1,348,892) were also obtained with the use of individual acetabular implants made of bone cement in hip replacement for periprosthetic infection in comparison with standard spacers (QALY – 0.07; CER – 2,845 801). The effectiveness of surgical treatment of patients with bone defects of type 2B and 3 according to AORI using individual implants during revision knee arthroplasty was 0.83 (CER – 494,236.8), using serial designs – 0.44 (CER – 939,489, 4). Conclusions. The use of individual implants in total replacement in patients with stage III hip osteoarthritis (according to N. S. Kosinskaya’s classification), as well as loosening of hip and knee implants, made it possible to achieve higher rates of effectiveness of surgical treatment in comparison with implantation of only serial structures. The use of additive 3D printing technologies in all cases, except knee joint replacement for bone defects of types 2B and 3 according to AORI, led to increased costs for treating patients. As a result of the clinical and economic analysis, it was revealed that the use of individual implants made using 3D printing in revision hip arthroplasty for IIIa and IIIb defects of the acetabulum, septic loosening of the components of a previously installed implants, as well as in re-replacement of the knee joint in the presence of AORI type 2B and 3 bone defects achieves the best cost-effectiveness ratio (CER) and is “strongly preferable” to implantation of serial constructs only.

Intra-articular corticosteroids for the treatment of osteoarthritis: A systematic review and meta-analysis on the comparison of different molecules and doses.

The purpose of this study was to quantify and compare the clinical relevance of the different intra-articular corticosteroids (CS) effects in vivo for osteoarthritis (OA) treatment. The search was conducted on PubMed, Cochrane,and Web of Science in October 2023. The PRISMA guidelines were used. Inclusion criteria: animal or human randomized controlled trials (RCTs), English language andno time limitation, on the comparison of different intra-articular CS for OA treatment. The articles' quality was assessed using the Cochrane RoB2 and GRADE guidelines for human RCTs, and SYRCLE's tool for animal RCTs. Eighteen RCTs were selected (16 human and 2 animal studies), including 1577 patients (1837 joints) and 31 animals (51 joints). The CS used were triamcinolone (14 humanand 2 animal studies), methylprednisolone (7 humanand 1 animal study), betamethasone (3 human studies)and dexamethasone (1 human study). All studies addressed knee OA except for three human and one animal study. A meta-analysis was performed on the comparison of methylprednisolone and triamcinolone in humans with knee OA analysing VAS pain at very short- (≤2 weeks), short- (>2and ≤4 weeks), mid- (>4and ≤8 weeks), long- (>8and ≤ 12 weeks),and very long-term (>12and ≤24 weeks). Triamcinolone showed better post-injection values compared to methylprednisolone at very short-term (p = 0.028). No difference in terms of VAS improvement was observed at any follow-up. The available preclinical and clinical literature provides limited evidence on the comparison of different CS, hindering the possibility of determining the best CS approach in terms of molecule and dose for the intra-articular injection of OA joints. Level I.

Hydraulic theory of pathogenesis of posttraumatic osteoarthritis of knee joints and perspectives of therapeutic measures

Hydraulic theory of pathogenesis of posttraumatic osteoarthritis of knee joints and perspectives of therapeutic measures