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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.

IntroductionCartilage lesions of the knee frequently result from acute traumatic injuries and pose significant challenges, particularly in young and active patients. While many involve osteochondral lesions, isolated chondral defects also occur. Traditional treatment focuses on fixation when viable subchondral bone is present; however, managing chondral-only lesions remains controversial due to limited intrinsic healing capacity.MethodsA systematic review was conducted, screening over 300 studies since August 2023. Inclusion criteria required (1) English-language studies, (2) reports on isolated chondral fragment fixation, and (3) a minimum of 6 months of follow-up. Eighteen studies met these criteria. Data on patient demographics, lesion characteristics, fixation methods, clinical outcomes, and functional scores were extracted.ResultsA total of 76 patients (mean age: 14.3 ± 3.7 years) were analyzed. Males comprised 80.3% of the cohort. The mean follow-up was 40.3 months (range: 7-171), and the mean chondral fragment size was 4.28 cm². The most common lesion locations were the lateral femoral condyle (34.2%), trochlea (32.2%), patella (25%), and medial femoral condyle (8.6%). Healing occurred in 96% of cases, and 86% of patients returned to sports at an average of 10.3 ± 6.1 months. Younger patients (≤14 years) had a significantly higher RTS rate (OR: 5.8; P = 0.0427). Functional scores (IKDC, KOOS, Marx, Tegner) demonstrated excellent postoperative outcomes.ConclusionDespite prior concerns regarding chondral-only fixation, this study demonstrates high healing rates and favorable functional outcomes. Direct fixation is a viable strategy, particularly in adolescents and young adults. Further prospective trials are needed to validate these findings.

Objective: To investigate the regulatory role of Toll-like receptor 3 (TLR3) in osteoarthritis (OA) progression, particularly its impacts on cartilage degradation, NF-κB-mediated inflammation, and autophagy activation.

Method: 1. Model Constuction: OA mouse model generated via anterior cruciate ligament transection (ACLT); LPS-induced inflammatory injury in murine ATDC5 chondrocytes; Histomorphological analysis of cartilage tissue using H&E and Safranine O staining. 2. Molecular Detection: TLR3 expression assessed by Western blot; Cartilage degradation markers (MMP-13, ADAMTS) and NF-κB pathway proteins analyzed via Western blot; Pro-inflammatory cytokine levels (IL-1β, TNF-α) quantified via RT-qPCR and Western blot. 3. Functional Assays: Cell viability examined via CCK-8 assay.

Results: 1. TLR3 Upregulation: TLR3 was highly expressed in OA cartilage and LPS-treated chondrocytes. 2. Cartilage Protection: TLR3 inhibition reduced cartilage erosion and proteoglycan loss in ACLT mice (confirmed by H&E and Safranine O staining); Downregulation of cartilage degradation markers (MMP-13, ADAMTS-5) observed in TLR3-knockdown models. 3. Anti-inflammatory Effects: TLR3 knockdown suppressed NF-κB activation, reducing IL-1β and TNF-α levels. 4. Autophagy Activation: Enhanced LC3-II/LC3-I ratio and Beclin-1 expression indicated TLR3 inhibition promotes autophagy.

Conclusion: TLR3 drives OA progression through dual mechanisms: 1. Pro-inflammatory Pathway: Activates NF-κB signaling to amplify cytokine release and cartilage matrix breakdown. 2. Autophagy Suppression: Inhibits autophagy-related proteins, impairing cellular homeostasis. Targeting TLR3 may represent a therapeutic strategy to balance inflammation and autophagy, potentially slowing OA progression in multi-joint involvement cases.

BackgroundOsteoarthritis (OA) is a chronic disease that seriously affects human health. Although biomarkers are vital to the discovery and therapy of OA, current research on OA-specific biomarkers remains limited, indicating a need for further expansion of this field of study.MethodsIn this study, differential genes in OA patients and normal samples in Genomics Expression Omnibus (GEO) database were analyzed for signaling pathway enrichment. Then, Weighted Gene Co-expression Network Analysis (WGCNA) combined with Least Absolute Shrinkage and Selection Operator (LASSO) analysis was used to obtain key genes associated with OA diagnosis, including BCL6 co-repressor (BCOR), Coiled-Coil Domain Containing 59 (CCDC59), Jun Proto-Oncogene (JUN), Lysine Demethylase 3A (KDM3A), L3MBTL Histone Methyl-Lysine Binding Protein 4 (L3MBTL4) and Zinc Finger Protein 292 (ZNF292). Finally, the role of KDM3A in OA cell model was verified by constructing KDM3A overexpression and silencing cell lines.ResultsIt was found that overexpression of KDM3A significantly downregulated β-catenin expression compared with the oe-NC group, thus affecting a series of biological processes in the OA cell model, specifically, increasing antioxidant capacity, reducing levels of inflammatory factors, and inhibiting extracellular matrix degradation.ConclusionThis study not only provided six key target genes for OA but also revealed the important role of KDM3A in OA, providing a reference for gene targeted therapy for OA patients.

IntroductionCellular senescence, i.e., a state of permanent cessation of cell division, is a hallmark of aging and has been associated with age-related diseases, most notably osteoarthritis (OA). Here we assessed senescence in chondrocytes, first in vitro after treatment with the mutagens N-ethyl-N-nitrosourea (ENU) or bleomycin, and then in vivo in cartilage samples from OA patients and control subjects.MethodsCellular senescence in cultured chondrocytes treated with mutagens was assessed by senescence-associated β-galactosidase (SA-β-gal) staining and by evaluating the expression levels of p16 and p21. Cellular senescence in human hip cartilage chondrocytes from OA patients or non-OA controls was similarly evaluated. Apoptosis in vitro was measured by the Bcl-2/Bax expression ratio, and in vivo by both TUNEL assay and the Bcl-2/Bax ratio.ResultsIn human articular cartilage, senescent cells were found to be significantly elevated in OA lesions of patients as compared with normal cartilage of non-OA control subjects. In vitro, senescence was observed in bleomycin-treated chondrocytes, but not in ENU-treated cells.ConclusionsOur findings demonstrate that cellular senescence is associated with the pathogenesis of OA, with DNA damage and mutations as potential contributing factors in OA-associated senescence.

ObjectiveOsteoarthritis (OA) is a degenerative joint disease characterized by cartilage degradation, causing severe pain and disability. Recent studies suggest that miR-450a-5p may regulate inflammatory pathways in OA. This study aimed to elucidate the role of miR-450a-5p in OA, providing a potential therapeutic target for the clinical treatment.MethodsCartilage tissues were collected from OA patients undergoing knee replacement surgery, and CHON-001 cells were treated with interleukin (IL)-1β to induce an OA model in vitro. Real-time quantitative polymerase chain reaction was used to detect the miR-450a-5p expression, and Western blot determined the lipopolysaccharide-induced tumor necrosis factor (TNF)-α factor (LITAF) expression. The targeting relationship between LITAF and miR-450a-5p was verified by dual-luciferase reporter assay. Cell proliferation and apoptosis were assessed using the Cell Counting Kit-8 assay and flow cytometry, respectively. Levels of IL-6, IL-10, and TNF-α were measured via enzyme-linked immunosorbent assay. In addition, Western blot was employed to detect the expressions of matrix metalloproteinase-3 (MMP-3), collagen III, and aggrecan in extracellular matrix (ECM).ResultsMiR-450a-5p expression was significantly down-regulated in OA tissues and IL-1β-induced CHON-001 cells (~60%), while LITAF expression was markedly increased (~1.8-fold). There was a negative correlation between miR-450a-5p and LITAF in OA tissues (r = -0.596, P < 0.01). MiR-450a-5p directly targeted and inhibited LITAF expression. Its overexpression promoted chondrocyte proliferation, reduced apoptosis and inflammatory cytokines, and mitigated ECM degradation.ConclusionsMiR-450a-5p inhibited LITAF expression, thereby attenuating apoptosis, inflammation, and ECM degradation in chondrocytes. It may serve as a promising therapeutic target for OA.

ObjectiveTo assess articular cartilage degeneration in anterior cruciate ligament (ACL) reconstructed knees as detected by MR T1rho and T2 mapping relative to controls and longitudinally at 3 months and 1 year after ACL reconstruction (ACLR).DesignTwenty-five patients with acute ACL injury were enrolled (13 women and 12 men; mean age 30.8), and 14 healthy controls were selected by sex and age matching. The affected knees of the ACLR participants were imaged using a 3.0T magnetic resonance (MR) scanner 3 months and 1 year after ACLR. Cartilage T1rho and T2 values were quantified for subcompartments in the full-thickness, superficial, and deep layers and were compared with the matched subcompartments of control knees. The influence of concomitant meniscal tears identified using proton density-weighted imaging (PDWI) was also investigated.ResultsIn the posterior lateral tibia, T1rho and T2 values were significantly higher in ACLR participants at 3 months and slightly decreased at 1-year compared to the control group. T1rho values in the medial compartment exhibited a significant increase at 1-year compared with those of control knees, while T2 showed no significance. In cartilage with medial meniscal tears, the T1rho values in multiple medial subcompartments were significantly higher than those in cartilage without medial meniscal tears, and this alteration was relatively detectable by T1rho.ConclusionsT1rho and T2 mapping is effective in evaluating cartilage degeneration following ACLR. T1rho may exhibit greater sensitivity for assessing the progression of early degeneration in the medial compartment after ACLR.