CARTILAGE最新文献

ObjectiveTo investigate the novel role of miR-708-5p in osteoarthritis (OA) and its potential as a therapeutic target through regulation of NOX4/NF-κB signaling.MethodsExpression levels of miR-708-5p were analyzed in OA cartilage using GEO datasets and validated in interleukin (IL)-1β-treated primary human chondrocytes. Gain- and loss-of-function experiments were performed using miR-708-5p mimics and inhibitors to evaluate its effects on inflammation, extracellular matrix metabolism, apoptosis, and oxidative stress. Direct targeting of NOX4 by miR-708-5p was confirmed through bioinformatic prediction, luciferase reporter assays, and rescue experiments.ResultsmiR-708-5p was significantly downregulated in OA cartilage and IL-1β-treated chondrocytes. Overexpression of miR-708-5p attenuated IL-1β-induced inflammatory responses by suppressing pro-inflammatory cytokines (IL-1β, IL-6, tumor necrosis factor [TNF]-α), inhibiting matrix-degrading enzymes (MMP3, ADAMTS-4), and enhancing anabolic factors (COL2A1, SOX9). miR-708-5p protected against chondrocyte apoptosis by regulating Bcl2/BAX and caspase-3 expression. It also increased chondrocyte proliferation in EdU assays and reduced reactive oxygen species (ROS) production. Mechanistically, miR-708-5p directly inhibited NOX4, reducing ROS generation and nuclear factor kappa B (NF-κB) activation. NOX4 overexpression reversed the protective effects of miR-708-5p, confirming the functional significance of this regulatory axis.ConclusionmiR-708-5p is downregulated in OA and exerts chondroprotective effects. These findings suggest that restoring miR-708-5p expression may effectively suppress the NOX4/NF-κB axis and modulate chondrocyte inflammation, oxidative stress, apoptosis, and matrix degradation.

ObjectiveTo evaluate the feasibility, safety and efficacy of allogeneic platelet-rich plasma (PRP) from responder donors to treat knee osteoarthritis (KOA) patients who showed negative response to autologous PRP.DesignThis pilot feasibility trial included KOA patients who did not respond to previous autologous PRP treatment. They were treated with intra-articular injections of allogeneic PRP from responder donors. Patients filled out Knee injury and Osteoarthritis Outcome Score (KOOS), Visual Analogue Scale (VAS), and Lequesne Index at baseline, 2, 6, and 12 months. Blood and PRP from donors and patients were analyzed, and a cell proliferation study was carried out.ResultsOf the 16 patients enrolled, 14 completed the study. KOOS pain subscale and VAS showed a significant increase from baseline to 12 months, and the Lequesne Index to 6 months (P < .005). Six patients (42.9%) showed a Minimal Clinically Important Improvement. No adverse reactions to allogeneic PRP were reported. The platelet number between donors and recipients was similar (P > .05) with a platelet concentration factor of 2.5. Donors were significantly younger than patients (P < .05) and presented higher levels of IGF-1 (P < .05). Cell bioactivity showed no differences between patient and donor PRP (P > .05).ConclusionThe use of allogeneic PRP from donor responders is a feasible and safe treatment for KOA patients who do not respond to autologous PRP. This treatment showed efficacy after 1 year of follow-up, suggesting a valid alternative for these patients, although further research is needed.EU Clinical Trials Register (https://www.clinicaltrialsregister.eu/). Registration number: 2021-001267-24.

ObjectiveThis study aimed to compare the clinical outcomes of microdrilling and microfracture for unipolar cartilage lesions of the distal femur.DesignPatients who underwent either microfracture or microdrilling and had postoperative magnetic resonance imaging (MRI) at 1 year were retrospectively reviewed. The morphology of the repaired cartilage tissue was evaluated using Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) 2.0 score. Functional outcomes were assessed using the International Knee Documentation Committee (IKDC) subjective, Lysholm scores, and Visual Analog Scale (VAS). In addition, the proportion of patients achieving improvement beyond the minimal clinically important difference (MCID) was analyzed.ResultsThe MOCART score was significantly higher in the microdrilling group. Among the variables, volume fill of the cartilage defect and integration into the adjacent cartilage showed significantly better results in favor of the microdrilling group. A higher proportion of patients achieved improvement in the IKDC subjective score beyond the MCID in the microdrilling group, whereas no significant differences were observed between the groups in Lyholm score and VAS.ConclusionMicrodrilling showed better outcomes in terms of the MOCART and IDKC subjective scores than microfracture, whereas Lysholm and VAS showed no significant differences. Further prospective studies are required to evaluate the results of these 2 procedures.

IntroductionLiterature on treatment outcomes in skeletally immature patients with osteochondral lesions of the talus (OLT) is scarce. As the healing of an OLT may be fundamentally different in a skeletally immature patient, more evidence is required focusing on this specific patient group. The primary aim of this study is to assess the conversion to surgery rate after initial non-operative management in skeletally immature patients with an OLT. The secondary aims of the present study are to assess and compare the clinical outcomes and reoperations after both non-operative and surgical treatment strategies at a mid- to long-term follow-up.MethodsAll skeletally immature patients at the moment of initial treatment, treated for their primary or non-primary OLT with a minimum follow-up duration of 2 years, were included in this study. Patients with concomitant injuries were excluded. All patients started with non-operative management. In case of failure of non-operative management, patients converted to Bone Marrow Stimulation (BMS) or fixation. The primary outcome was the conversion to surgery rate after initial non-operative management. Secondary outcomes consist of reoperations at mature and immature age, pain during weight bearing, measured by the numeric rating scale (NRS), NRS of pain during rest, NRS during stair climbing, Berndt and Harty outcome question, Foot and Ankle Outcome Score (FAOS) and Short Form-36 (SF-36) and the patient satisfaction rate regarding the received treatment.ResultsA total of 52 patients, 54% female, mean age of 13.6 years, were included in this study. Median follow-up duration was 81 months (range = 24-265 months). Seventeen patients received non-operative treatment as final treatment. In total, 35 (67%) out of 52 patients required surgical treatment after initial non-operative management, of which 14 underwent BMS and 20 had fixation while skeletally immature, 1 patient that had surgical treatment as an adult was excluded for further analysis. The median NRS of pain during weight bearing was 1 (interquartile range [IQR] = 0-2), 1 (IQR = 0-3), and 0 (IQR = 0-0.5) in the (sustained) non-operative, BMS, and fixation groups, respectively (P < 0.012). No significant differences in clinical outcomes between the different treatment groups could be observed. No complications occurred after surgical treatment. Reoperation rates were 21% and 20% in the BMS and fixation groups, respectively.ConclusionsThe most important finding of this study is that 67% of the patients receiving initial non-operative management for OLTs ultimately required surgery.Level of evidenceLevel III, cross-sectional comparative study.

ObjectiveTo evaluate radiological, short-term, and medium-term clinical outcomes of arthroscopic non-concentrated iliac bone marrow stimulation (BMS) for small talar cystic osteochondral lesions of the talus (OLTs).DesignForty-three cases underwent this modified BMS between 2014 and 2019 were evaluated. Clinical outcomes were assessed by the Foot and Ankle Ability Measure (FAAM) Activities of Daily Living (ADL) and Sports Subscales (SS). Regenerated tissue was evaluated with the Magnetic Resonance Observation of Cartilage Repair Tissue scales (MOCART-2.0). Subgroup analysis based on locations and concomitant anterior talofibular ligament (ATFL) injuries.ResultsThe average diameter and depth of cysts were 6.97 ± 1.53 mm and 5.47 ± 1.10 mm, respectively. At a mean follow-up of 57.02 ± 19.61 months, FAAM-ADL and FAAM-SS improved significantly (45.65 ± 4.56 to 74.77 ± 8.03 and 12.63 ± 1.87 to 26.67 ± 3.41, respectively). From short-term to medium-term, FAAM-ADL revealed a minor decline (75.53 ± 7.76 vs. 74.77 ± 8.03, P = 0.421); FAAM-SS improved (25.37 ± 3.51 vs. 26.67 ± 3.41, P = 0.089). Medial lesions demonstrated favorable outcomes compared to lateral lesions [FAAM-ADL (77.04 ± 7.23 vs. 70.75 ± 8.10, P = 0.013), FAAM-SS (28.08 ± 2.40 vs. 24.19 ± 3.51, P < 0.001), and MOCART-2.0 (85.19 ± 11.27 vs. 71.88 ± 11.09, P < 0.001)]. Lateral lesions indicated higher rates of major hypertrophy (56.25% vs. 7.69%) and split-like defects (56.25% vs. 15.38%). The ATFL injuries did not significantly influence revision rates (15.8% vs. 4.2%, P = 0.439).ConclusionsArthroscopic non-concentrated iliac BMS demonstrated stable outcomes for small cystic OLTs. Lateral lesions were associated with inferior subjective scores and relatively higher rates of irregular fibrocartilage.

IntroductionThis study investigates the association between vascular endothelial growth factor (VEGF) levels and platelet-rich plasma (PRP) treatment outcomes, as well as the role of other cytokines in symptom improvement.MethodsThirty-nine patients with knee osteoarthritis (KOA) who underwent PRP therapy were analyzed. Cytokine and growth factor levels in PRP were measured, and clinical outcomes were assessed using the visual analog scale (VAS) and the Knee Injury and Osteoarthritis Outcome Score (KOOS) before and 1 month after a single intra-articular PRP injection. Correlations between cytokine levels and clinical improvements were evaluated.ResultsAge correlated positively with C-X-C motif chemokine ligand 9 (CXCL9) (r = 0.50, p < 0.001). Body mass index (BMI) correlated negatively with interleukin-10 (IL-10) and positively with interleukin-18 (IL-18). Elevated IL-18 levels correlated with worse KOOS-Activities of Daily Living (ADL) improvements (r = -0.410, P = 0.01), linking obesity, inflammation, and reduced PRP efficacy. While VEGF showed no association with patient background, higher VEGF levels correlated with poorer VAS score improvements (r = -0.381, P = 0.017), suggesting reduced PRP efficacy. A VEGF cut-off of 120 pg/ml identified non-responders with 82.6% sensitivity, 56.2% specificity, and an area under the curve (AUC) of 0.71. Among patients with VEGF ≥120 pg/ml, the response rate was 26.9%, while those with VEGF <120 pg/ml had 75%.ConclusionsHigher VEGF concentrations in PRP were associated with reduced short-term clinical efficacy in patients with knee osteoarthritis. VEGF may serve as a predictive biomarker for PRP treatment response.

Background. Post-traumatic chondral and osteochondral lesions can be treated with autologous chondrocyte implantation (ACI), but the high cost of autologous cell expansion under strict Good Manufacturing Practice (GMP) regulations limits patient access. Stem cell-based advanced therapy medicinal products (ATMPs) offer more cost-effective alternatives, with human induced pluripotent stem cells (iPSC) showing great promise due to their expandability, low immunogenicity, commercialization potential, and fewer ethical concerns. Aim. To develop a protocol to direct iPSC through a mesenchymal stage into chondroprogenitors (iCHOp), resembling autologous chondroprogenitor cells used in ACI. Methods. The derived chondroprogenitor cells were expanded in monolayer and in 3-dimensional (3D) cultures and subsequently analyzed using transcriptomic profiling via RNA sequencing and reverse transcription quantitative polymerase chain reaction and compared with ACI chondrocytes. Results. Transcriptomic profiling confirmed successful differentiation, with iCHOp showing 83% similarity to ACI chondrocytes. Further 3D culture maturation led to upregulation of chondrogenesis-related genes and activation of cartilage-specific pathways. Histological analysis confirmed extracellular matrix production, including proteoglycans, collagen, and versican. Furthermore, the protocol's reproducibility was demonstrated using 3 distinct iPSC lines, successfully expanded in both serum-containing and defined serum-free media. Conclusion. Our optimized approach yields iCHOp with phenotypes closely matching ACI chondrocytes, offering a solid foundation for further development and potential clinical applications in cartilage repair.

PurposeThis study aimed to identify potential impinging and shear stress-inducing factors in knees with medial meniscus posterior horn horizontal tears (MMPHHT) using magnetic resonance imaging (MRI) in middle-aged patients with meniscal degeneration.Materials and MethodsWe retrospectively analyzed and compared consecutive patients with MMPH signal changes or MMPHHT on MRI from January 2015 to January 2022. After 1:1 propensity score matching, 80 patients in each group were analyzed. Bony impinging factors, including the femoral condylar offset ratio, the ratio of posterior condylar offset (PCO) to tibial width, posterior medial tibial plateau concavity, and the medial tibial slope, were assessed. Soft tissue impinging factors, such as the MMPH coverage ratio, presence of medial femoral condyle focal cartilage defects or posterior tibial osteophytes, were also analyzed.ResultsDemographic data did not differ between MMPHHT and MMPH signal change groups. MMPHHT group showed increased medial tibial slope (5.33 ± 2.05° vs 4.21 ± 2.58°, P = .003), higher incidence of posterior medial tibial plateau concavity (P = .040), greater MMPH coverage ratio (0.43% ± 0.05% vs 0.41% ± 0.04%, P = .022), and more posterior tibial osteophytes (P = .012). Multivariate logistic regression identified higher medial tibial slope (OR = 1.288, P = .016), MMPH coverage ratio (OR = 1.369 × 10⁴, P = .020), and posterior tibial osteophytes (OR = 4.525, P = .009) as independent factors associated with MMPHHT.ConclusionIn conclusion, we have determined several anatomical contributing factors related to MMPHHT. Such factors may be useful in understanding the progression of meniscus degeneration in early OA knees. Furthermore, addressing correctable factors during surgery such as tibia slope correction or osteophytectomy may improve repair results of MMPHHT in the future.

BackgroundTrapeziometacarpal osteoarthritis (TMO) is a prevalent degenerative condition. While conservative treatments such as physiotherapy, drugs, and corticosteroid or hyaluronic acid injections offer symptomatic relief, their long-term efficacy remains debated. A recent study has explored collagen-based fillers as an alternative, but long-term clinical outcomes are still under investigation.MethodsThis study enrolled 64 patients diagnosed with TMO, stratified into 2 groups based on the Eaton-Littler classification (grade 1-2: group A; grade 3-4: group B). All patients received a percutaneous intra-articular injection of a cell-free collagenic hydrogel under ultrasound guidance. Outcomes were assessed more than 2 years using the Numeric Rating Scale (NRS) for pain, Jamar and Pinch tests for grip strength, and the Disability of the Arm, Shoulder, and Hand (DASH) questionnaire.ResultsIn both groups, all studied variables demonstrated a significant improvement (P < 0.001) that was sustained in the long term. Notably, greater improvement was observed in strength tests for Group A patients and in the DASH score for Group B patients. The most substantial improvement occurred between 2 and 6 months post-procedure. No adverse events were reported.ConclusionCollagen-based filler injections provide long-term pain relief and functional improvement in TMO, representing a promising minimally invasive treatment option.Trial registry name:NCT06881186.