PurposeTo report 24-month clinical outcomes, surgery-free survivorship, and radiological variations after Calcium-Phosphate (CaP) Subchondroplasty (SCP) procedures in patients with symptomatic knee bone marrow lesions (BMLs) in the context of mild-to-moderate knee osteoarthritis (OA).MethodsAdults with tibiofemoral BMLs (Kellgren-Lawrence [KL] 1-3) underwent CaP SCP using a standardized protocol. Prespecified outcomes were KOOS (primary: KOOS Pain), EQ-5D-5L, and pain NRS at baseline, 1, 3, 6, 12, and 24 months; surgery-free survivorship (Kaplan-Meier); and structural status by KL and MOAKS (available-case imaging). Analyses compared time points with paired tests and 95% CIs.ResultsNinety-two knees were treated. KOOS Pain improved from 45.9 ± 14.3 preoperatively to 81.3 ± 18.1 at 24 months (p < .0001). All other KOOS subscales improved from baseline to 24 months (all p < .0001) and pain NRS decreased from 6.8 ± 1.5 to 3.3 ± 2.6 (p < .0001). Kaplan-Meier surgery-free survivorship was 97.7% (95% CI, 90.9-99.4) at 12 months and 91.5% (95% CI, 82.9-95.8) at 24 months; 7/92 knees (7.6%) underwent reoperation. KL distributions showed no significant change versus baseline at 12 months (p = .5089) or 24 months (p = .9801). MOAKS improved at 12 months (p = .0435) but not at 24 months (p = .2517) in the available MRI subset. No serious device-related adverse events were observed.ConclusionIn BML-positive knees with KL 1-3 OA, SCP yielded large and durable improvements in pain, function, and health-related quality of life through 24 months, with >90% surgery-free survivorship and radiographic stability.
PurposeMedial open-wedge high tibial osteotomy (MOW-HTO) is effective for correcting varus knee deformity but may unintentionally affect ankle joint alignment. This study investigated radiographic factors associated with postoperative ankle alignment changes following valgus-producing MOW-HTO.MethodsA retrospective analysis was conducted on a prospective cohort of 50 knees in 49 patients (mean age 46.3 ± 8.2 years). Patients were included if they underwent MOW-HTO between 2016 and 2024, were enrolled in the hospital knee registry, and had both pre-and postoperative whole-leg radiographs available. These weight-bearing long-leg radiographs were used to assess tibial bone deformity and ankle joint alignment. Postoperative ankle alignment was classified as deviating closer to neutral or further from neutral. Correlation analyses and within- and between-group comparisons were performed, with significance set at p < 0.05.ResultsAfter MOW-HTO in varus-shaped knees, all alignment parameters shifted toward valgus. Tibial deformity predominantly originated from the distal tibia, with a medial center of rotation of angulation (CORA), reflecting an overall valgus-shaped tibia. Distal tibial valgus showed a strong correlation with talar orientation relative to the ground (ρ = 0.81, p < 0.001). Patients deviating further from neutral had nearly 5° more distal tibial valgus than those deviating closer to neutral (p < 0.001), and more frequently showed an overall valgus-shaped tibia (p < 0.01). Additionally, larger correction angles were moderately associated with greater valgus shift of the ankle (ρ = -0.44, p < 0.001).ConclusionMOW-HTO results in a valgus shift of the talar orientation, particularly in patients with preoperative distal tibial valgus, an overall valgus-shaped tibia, and larger correction angles. Thorough preoperative assessment of tibial morphology is essential to better anticipate postoperative ankle alignment changes.
BackgroundArticular cartilage and the inner (white) zone of the knee meniscus are characterized by minimal vascularity, a dense extracellular matrix (ECM), and cellular metabolism adapted to diffusion-limited oxygen and nutrient delivery. These features support long-term load-bearing function but limit intrinsic healing.1-3HypothesisRather than framing avascularity as an "evolutionary optimization," we propose a mechanobiological trade-off in which anti-angiogenic maintenance of avascularity helps preserve matrix continuity and load support, while constraining vascular-dependent repair.1,4Evidence/ConceptAnti-angiogenic regulation is plausible in the inner meniscus, where chondromodulin-I (ChM-I) is enriched and functionally inhibits endothelial cell proliferation.4 Metabolic compatibility provides a complementary biological rationale: hypoxia-responsive signaling (including HIF-1alpha) supports chondrocyte survival and matrix homeostasis in avascular cartilage, and classic biochemical observations in cartilage are consistent with limited oxidative capacity and strong dependence on glucose availability.8,10 Mechanically, the clinically relevant question is whether vascular "space" formation within an otherwise continuous, hydrated ECM measurably alters stiffness- and fluid-pressurization-dependent load support.5-7 We treat finite-element analysis (FEA) only as an illustrative sensitivity concept: channel-like discontinuities within a composite are expected to increase local shear/strain concentration and reduce apparent compressive stiffness, depending on geometry and constitutive assumptions.5-7ConclusionThis framework yields testable predictions for explants and engineered constructs and may guide regenerative strategies that improve transport without mechanically compromising load-bearing architecture.
Purpose Safety and efficacy of allogeneic integrin α10β1-selected MSCs (integrin α10-MSCs) have been shown in two post-traumatic osteoarthritis (OA) equine models. The aim of this study is to evaluate safety, tolerability and preliminary efficacy of allogeneic integrin α10-MSCs in human symptomatic knee OA. Methods In a first-in-human prospective multicentre phase I/IIa dose escalation study, 24 patients (41-75 years, Kellgren-Lawrence grade II-III knee OA) were treated with a single intra-articular injection of 4, 8 or 16 million integrin α10-MSCs. Safety and tolerability were assessed by adverse events, electrocardiography, vital signs, and physical and laboratory examinations. Clinical outcome was measured by visual analogue scale (VAS) for pain and Knee injury and Osteoarthritis Outcome Score (KOOS). Structural outcomes were assessed by X-ray and MRI. The total follow-up period was 24 months for the highest dose and 18 months for the lower doses. Results The most frequently reported study drug-related adverse events were injection site pain, joint swelling and injection site movement impairment. All doses showed sustained improvements in pain and function, whereas the 16 million dose cohort showed earlier effects. The 16 million dose cohort also showed a reduction in bone marrow lesions, signs of an improved cartilage quality by T2* relaxation time, and a stable medial minimum joint space width. Conclusions This study demonstrated safety and efficacy of intra-articular injection of integrin α10-MSCs for the treatment of mild to moderate knee OA. At a dose of 16 million integrin α10-MSCs, a potentially quick and long-lasting therapeutic effect, supportive of disease-modification, was evident.
BackgroundExtracellular vesicles (EVs) mediate many of the reparative effects of cell-based therapies for osteoarthritis; however, the influence of EV source on cartilage repair and systemic immune responses remains unclear. Cartilage-resident chondroprogenitors represent lineage-biased cell populations with enhanced chondrogenic stability when compared with BM-MSCs and chondrocytes.MethodsEVs were isolated from human BM-MSCs, chondrocytes, fibronectin adhesion assay-derived chondroprogenitors (FAA-CPs), and migratory chondroprogenitors (MCPs) obtained from non-diseased donors. EVs were characterised for size, surface markers, and protein content. Osteoarthritis was induced in Wistar rats using the monosodium iodoacetate model. EVs (40 µg) were administered intra-articularly once weekly for six weeks. Each treatment group included 12 joints, with sham and OA controls. Cartilage repair was assessed by routine histological evaluation, collagen immunohistochemistry and modified Mankin scoring. Systemic immune responses were evaluated using splenic IL-6 and TNF-α expression.ResultsAll EV-treated groups demonstrated improved cartilage morphology compared with controls. EVs derived from cartilage-resident cells consistently promoted superior cartilage repair compared with BM-MSC-derived EVs, with improved proteoglycan retention, collagen type II deposition, and lower modified Mankin scores. FAA-CP and MCP EVs showed comparable reparative profiles and modestly outperformed chondrocyte-derived EVs. BM-MSC EVs exhibited the lowest splenic IL-6 and TNF-α expression, indicating stronger immunomodulatory effects, while cartilage-resident EVs showed immune profiles similar to chondrocytes.ConclusionEV source significantly influences cartilage repair and immunological behaviour in early osteoarthritis. Cartilage-resident cell EVs demonstrate enhanced repair, whereas BM-MSC EVs retain stronger immunomodulatory capacity. These findings support rational EV source selection for cartilage regeneration strategies.
Objective Mechanical loading is critical for chondrocyte function and cartilage matrix production, yet its effects on clustered chondrocytes in end-stage osteoarthritis and on chondrosarcoma cells remain poorly understood. This study investigated how cyclic compression influences chondrocytes and chondrosarcoma cells cultured either as single cells or as micromasses. Methods An organ-on-chip platform was used to apply cyclic compression to chondrocytes and chondrosarcoma cells embedded in agarose as single cells or micromasses mimicking chondrocyte clusters. Deformation during loading was assessed, and after four days of stimulation, gene and protein expression of cartilage markers and extracellular matrix components were analyzed. Results Chondrocyte micromasses deformed less than single cells and showed behavior resembling chondrosarcoma cells and their micromasses. All four culture models exhibited distinct mechanobiological responses after four days of compression. Mechanical loading promoted collagen I reorganization in micromasses and increased ACAN and COL2A1 expression, with enhanced matrix deposition aligned with the loading direction in one chondrocyte donor and one chondrosarcoma cell line. Semi-quantitative imaging suggested trends toward ECM deposition along the loading axis in some micromass conditions. Conclusion In this agarose-based organ-on-chip proof-of-concept model, cellular organization was associated with distinct responses to cyclic compression. These findings should be interpreted as model-specific observations from one OA donor and one chondrosarcoma cell line, and require validation in additional donors, cell lines, matrices, and loading conditions before broader conclusions can be drawn.
ObjectiveEvaluate the association of sex and age at surgery with time to total knee arthroplasty (TKA) following knee cartilage surgery in UK Biobank (UKB) participants.DesignParticipants with a history of knee cartilage surgery were classified into four surgical subgroups: cartilage repair, debridement, microfracture, and unicompartmental knee arthroplasty. Time from index surgery to primary TKA in each group was analysed using the Kaplan-Meier method and the sexes compared using log-rank tests. Cox proportional hazards regression evaluated associations between age at surgery, sex, and surgery type with risk of progression to TKA.ResultsThe study included 1,967 males and 1,741 females. Log‑rank testing demonstrated significant sex‑based differences in time to TKA following debridement (P = 0.002) and microfracture (P = 0.003), with shorter TKA‑free survival observed in females. Cox regression showed that female sex was associated with a higher hazard of progression to TKA compared with male sex (hazard ratio [HR] = 1.19, P = 0.021). Increasing age at surgery was associated with increased risk (HR = 1.05 per year, P < 0.0001).ConclusionFemale sex and older age at surgery were associated with a higher risk of progression to TKA following cartilage surgery. Sex‑specific differences in time to TKA were most evident after debridement and microfracture. These findings describe associations observed within the constraints of available UKB data.
Objective This study investigated the dose-dependent cytotoxicity and immunomodulatory effects of intra-articular local anaesthetics (lidocaine, mepivacaine, levobupivacaine) and corticosteroids (dexamethasone, methylprednisolone, methylprednisolone acetate) on canine fibroblast-like synoviocytes (FLS) in vitro . We evaluated cell viability and the expression of IL-6 and MMP-9. Methods Canine FLS were exposed to increasing concentrations of intra-articular agents. Cell viability was determined via MTT assays. Immunomodulatory effects were assessed via ELISA for IL-6 and gelatin zymography for MMP-9 activity after TNF-α stimulation with IC 50 concentrations. Results All agents exhibited dose-dependent cytotoxicity. Dexamethasone was most cytotoxic (IC 50 ≈ 3.4×10 -4 mg/mL) but selectively inhibited TNF-α-induced MMP-9 activity without affecting IL-6 or inducing cytotoxicity at its IC 50 . Mepivacaine significantly inhibited MMP-9 activity by 40% at 1 mg/mL and uniquely induced IL-6 in unstimulated cells. Lidocaine, methylprednisolone, and methylprednisolone acetate suppressed TNF-α-induced IL-6 expression. Conclusions Commonly used intra-articular agents induce dose-dependent cytotoxic effects on canine FLS at clinically relevant concentrations. This study provides the first evidence of species-specific responses for mepivacaine, levobupivacaine, and dexamethasone in canine FLS, highlighting mediator-specific and concentration-dependent effects crucial for optimizing intra-articular therapies in veterinary and translational medicine.
Objective Osteoarthritis (OA) is characterized by progressive cartilage degeneration driven by inflammation-induced chondrocyte injury, while effective disease-modifying therapies are still lacking. Exosome-based cell-free approaches are emerging as promising alternatives, but their key molecular mediators remain incompletely defined. Design Adipose-derived stem cells (ADSCs) were pretreated with platelet-rich plasma (PRP) to enhance exosomal function. Isolated exosomes were characterized, and LINC01106 expression was modulated by overexpression or knockdown. Interleukin (IL)-1β-stimulated chondrocytes were used to assess apoptosis, inflammatory cytokine secretion, oxidative stress, and extracellular matrix degradation. The LINC01106/miR-34a-5p/SIRT1 axis was examined using luciferase reporter assays, quantitative real-time polymerase chain reaction (PCR), Western blotting, and immunofluorescence. Results PRP pretreatment markedly increased LINC01106 enrichment in ADSC-derived exosomes. LINC01106-rich exosomes significantly reduced chondrocyte apoptosis, suppressed tumor necrosis factor-α (TNF-α) and IL-6 secretion, alleviated oxidative stress, and attenuated matrix metalloproteinase (MMP)-mediated matrix degradation under IL-1β stimulation. Mechanistically, LINC01106 acted as a competing endogenous RNA that sequestered miR-34a-5p, thereby restoring SIRT1 expression. Rescue experiments demonstrated that miR-34a-5p overexpression or SIRT1 silencing abolished these protective effects. In addition, LINC01106-enriched exosomes inhibited nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) pathway activation in a SIRT1-dependent manner. Conclusion PRP-stimulated ADSC-derived exosomes confer potent chondroprotective effects through the LINC01106/miR-34a-5p/SIRT1 pathway, highlighting a promising cell-free therapeutic strategy for OA.
Background Cell-based cartilage repair is limited by loss of chondrogenic potential during in vitro expansion. Fibronectin (FN)-based selection may enrich progenitor-like cells with better matrix-forming ability, but its long-term effect on ECM production by hiPSC-derived chondroprogenitors (hiCPCs), their derived chondrocytes (hiCHOs), and primary articular chondrocytes (hACs) from lesioned or preserved areas remains unclear.Methods We here compared cartilage ECM formation by hiCPCs/hiCHO's and hACs, with or without FN selection, over extended passaging using 3D organoids. Histology and quantitative image analysis were performed to assess tissue quality across passages.Results Chondrogenicity in hiCPCs transiently improved early-stage ECM production upon FN-based selection, but accelerated loss of chondrogenicity was seen in later passages. This was evidenced by diminished matrix staining and structural degradation from passage 4 onward. In contrast, hACs from both preserved and lesioned cartilage maintained stable matrix-forming ability across passages, independent of FN-based selection.Conclusion FN-based selection does not preserve long-term chondrogenicity in hiCHOs and may even impair it during extended culture. In contrast, primary cell sources, regardless of cartilage integrity, demonstrate greater and robust chondrogenic capacity without requiring progenitor enrichment. These findings highlight the intrinsic ability of hACs and question the utility of FN-based selection in cartilage tissue engineering.
Introduction Return to work (RTW) is a key goal for patients treated for osteochondral lesions of the talus (OLT).Aim The primary objective of this review is to determine the RTW after surgical treatment of an OLT.Methods After preregistration, MEDLINE (PubMed), Embase and Cochrane Library were screened by two authors. RTW time and rate were extracted, and pooled if sufficient data was available. Two authors assessed methodological quality using the MINORS criteria.Results A total of 18 studies were included for which 399 patients reported RTW rate and/or time. The overall methodological quality of the studies was poor. The RTW time ranged from 2 to 11 weeks post-operatively and varied across surgical techniques. The overall RTW rate was 93%, with arthroscopic procedures averaging 96%, and open procedures averaging 91% RTW.Conclusion After surgical treatment of OLTs, 93% of patients returned to work. Time to RTW ranged from 2 to 11 weeks, although reporting was heterogeneous and methodological quality was generally low. Future studies should include RTW as a core outcome and report work-related restrictions more consistently.
Objective This study investigated whether hyperbaric oxygen (HBO) therapy, initiated after disease establishment, exerts disease-modifying effects in a rat model of anterior cruciate ligament transection (ACLT)-induced post-traumatic osteoarthritis (PTOA). Design Thirty-six Sprague-Dawley rats underwent ACLT surgery. HBO therapy commenced at Week 11 (established OA phase) and continued for 6 weeks. Outcomes were assessed using Von Frey testing, multimodal 7T MRI (T2* quantification and pharmacokinetic DCE-MRI), and histopathology. Results By Week 10, ACLT induced significant mechanical allodynia, T2* prolongation, and SCB perfusion abnormalities ( A increase; k ep , k el decrease). Following HBO intervention, the ACLT+HBO group exhibited a marked recovery in mechanical withdrawal threshold and significantly lower T2* values compared to the ACLT-only group ( p < 0.01). DCE-MRI demonstrated that HBO restored clearance kinetics ( k el , k ep ) and suppressed pathological blood volume ( A ), effectively remediating subchondral venous congestion. Histologically, HBO reduced OARSI scores and suppressed α-SMA-positive vascular invasion across the tidemark. These findings suggest that HBO therapy may alleviate PTOA by suppressing catabolic activity and normalizing pathological subchondral angiogenesis. Conclusions HBO therapy, initiated post-pathogenesis, effectively attenuates nociception and preserves cartilage integrity by restoring subchondral microcirculatory homeostasis. These findings establish HBO as a potent, non-invasive disease-modifying strategy for PTOA.
Objective Osteoarthritis (OA) is an age-related musculoskeletal disorder lacking effective disease-modifying therapies and early diagnostic biomarkers. This study aimed to identify serum proteins that could indicate the occurrence of knee OA (KOA) and correlate with patients' pain and functional impairment.Design/Methods Fasting serum samples were collected from controls (n = 8) and patients with end-stage KOA at baseline (n = 8) and 12 months after total knee arthroplasty (n = 8). Proteomics analysis was conducted with liquid chromatography-mass spectrometry, followed by univariate and multivariate statistics and pathway analyses by MetaboAnalyst and STRING. Partial correlations were calculated with R, adjusted for sex, age, and body mass index, using a linear regression model.Results 151 proteins were upregulated and 5 proteins downregulated in baseline KOA compared to control. These proteins were linked to the complement system, immune response, coagulation, inflammatory response, calcium homeostasis, and extracellular matrix remodeling. Of these, complement factor I showed strong biomarker potential. Several proteins emerged as statistically significant predictors of cartilage loss, pain sensitivity, physical function, and corticospinal excitability. Systemic alterations persisted 12 months after surgery.Conclusion Serum proteins may serve as biomarkers of KOA, reflecting disease-related immune, inflammatory, and tissue-remodeling processes that persist after joint replacement.
Objective To compare alignment parameters in bilateral lower extremities and evaluate the effect of contralateral limb on hip-knee-ankle angle (HKAA) longitudinally. Methods Native bilateral lower extremities of 3,045 Korean patients with long-leg radiographs were followed for progression of knee osteoarthritis. Concordance rates of Functional Knee Phenotypes (FKPs) and Coronal Plane Alignment of the Knee (CPAK), the proportion of patients with identical bilateral subtypes, were assessed. Varus, neutral, and valgus alignments were defined as baseline HKAA ≤177°, 177°< HKAA <183°, and HKAA ≥183°, respectively. Multivariable linear regressions for follow-up HKAA were conducted. Results Concordance rates for FKPs and CPAK were 41.6% (95% confidence interval: 39.9-43.4%) and 53.5% (51.7-55.2%), respectively, at baseline and 35.5% (33.8-37.2%) and 55.4% (53.7-57.2%) at a mean 4.0-year follow-up. Contralateral parameters, Kellgren-Lawrence grade ( P = 0.005) in bilateral varus group, medial proximal tibial angle (MPTA) ( P = 0.046) in ipsilateral varus-contralateral neutral group, MPTA, and mechanical lateral distal femoral angle in bilateral neutral ( P < 0.001; P = 0.012, respectively) and valgus ( P = 0.003; P = 0.004) groups, were associated with follow-up HKAA. However, their standardized β values were smaller than ipsilateral values. Conclusion Concordance rates of FKPs and CPAK between bilateral limbs were 41.6% and 53.5% at baseline, respectively. Contralateral parameters have limited influence on coronal alignment progression compared with ipsilateral parameters.
Introduction Osteoarthritis (OA) is more common in women, suggesting a link to estrogen. Estrogen supports cartilage homeostasis and metabolism via two receptors: ERα and ERβ. Mechanical stress is the primary cause of OA and affects cellular functions, including receptor activity. The link between excessive mechanical stress and ERs in cartilage is poorly understood. This study examined ER expression changes in chondrocytes under mechanical stress and the role of estrogen in cartilage degradation and ER regulation. Methods ATDC5 chondrocytes were treated with 17β-estradiol (E2; 1.0 × 10⁻⁷M) and subjected to cyclic tensile strain using the Flexcell Tension Plus FX-2000. Total RNA and proteins were extracted, and IL-1β and MMP-13 expression were analyzed using RT-PCR and western blotting. RT-PCR was used to examine the expression of ERα and ERβ. Results The CTS group had significantly downregulated ERα expression at all time points and upregulated ERβ expression after 3 and 6 hours compared with controls. In the E2+CTS group, IL-1β and MMP-13 expression were suppressed after 3 and 6 hours, coinciding with significant upregulation of ERβ compared with the CTS group. Conclusions Estrogen exerts a chondroprotective effect under excessive mechanical stress, suggesting that ERβ mediates this effect.
Introduction Osteoarthritis is considered a whole-joint disease involving subchondral bone. Intraosseous therapies such as calcium phosphate (CaP), platelet-rich plasma (PRP), and mesenchymal stem cells (MSCs) offer joint-preserving options for knee osteoarthritis (OA). Purpose To critically appraise and update the clinical evidence on intraosseous injections for knee osteoarthritis, focusing on safety, functional outcomes, need for retreatment, and conversion rates to total knee arthroplasty (TKA). Methods A systematic review of PubMed, Embase, and Cochrane was conducted following PRISMA guidelines and PROSPERO registration (CRD420251104989). Clinical studies reporting outcomes of intraosseous injections with CaP, PRP, or MSCs for knee osteoarthritis with ≥5 patients and ≥6 months of follow-up were included. Methodological quality was assessed using the modified Coleman Methodology Score and Cochrane Risk of Bias 2.0 tool. Results Twenty-four studies involving 1,109 patients (mean age, 55 years; mean follow-up, 38 months) met inclusion criteria: 10 on CaP, 6 on PRP, and 8 on MSCs. Five were randomized controlled trials (RCTs). Most studies reported significant improvements in pain and function. CaP injection outcomes were variable, with TKA conversion rates ranging from 1.3% to 45%. PRP and MSCs studies showed favorable safety profiles and lower conversion rates. Long-term MSCs data indicated sustained relief and delayed TKA over up to 15 years. However, overall study quality was modest, with only one RCT rated as low risk of bias. Conclusion Intraosseous injections may improve symptoms and delay arthroplasty in selected patients with knee OA, with MSCs showing the most favorable long-term results. PRP appears to be a safe option whereas CaP outcomes are more variable. Standardized protocols and high-quality RCTs with long-term follow-up are needed to optimize patient selection and treatment efficacy.
ObjectiveUmbilical cord-derived mesenchymal stromal cells (UC-MSCs) are a promising treatment for knee osteoarthritis (KOA). This study aimed to (1) characterize early synovial fluid biomarker changes after intra-articular UC-MSCs therapy in advanced KOA and (2) explore their relationship with short-term clinical outcomes.MethodsIn this prospective, single-arm case series, 15 patients with advanced KOA (Kellgren-Lawrence III-IV) scheduled for total knee arthroplasty received a single intra-articular injection of 20 × 106 allogeneic UC-MSCs. Synovial fluid was aspirated at baseline and approximately 6 weeks post-injection. A panel of 29 soluble biomarkers related to inflammation, matrix remodeling, immune signaling, angiogenesis, and metabolism was quantified using multiplex immunoassays. Clinical status was evaluated with Patient-Reported Outcome Measures (PROMs) before and at a mean of 48 ± 18 days after the injection. Paired differences were analyzed using the Wilcoxon signed-rank tests.ResultsSignificant post-treatment differences were observed in biomarkers associated with extracellular matrix turnover (Matrix Metalloproteinase [MMP]-1, MMP-3, MMP-7, Cartilage Oligomeric Matrix Protein [COMP]), vascular remodeling (Vascular Endothelial Growth Factor [VEGF], Vascular Cell Adhesion Molecule [VCAM]-1), immune modulation (interleukin [IL]-8), and metabolic or structural regulation (Leptin, dickkopf [Dkk]-1). Most PROMs demonstrated significant improvements. These findings describe molecular changes in synovial fluid observed after intra-articular UC-MSC administration.ConclusionsIn this prospective single-arm cohort, intra-articular UC-MSC administration was feasible and well tolerated, and we observed pre-post changes in synovial fluid biomarkers and patient-reported outcomes. These findings do not establish causality and warrant confirmation in controlled studies. The study was registered at Clinicaltrials.gov: Mechanisms of Treatment Effects Using Cultured, Allogeneic Mesenchymal Stromal Stem Cells (MSCs) in Knee Osteoarthritis, NCT06078059, https://clinicaltrials.gov/study/NCT06078059?intr=NCT06078059.
Objective This study developed and optimized a deep learning model to automate OARSI-based histologic scoring of mouse medial tibial cartilage.Design Safranin-O-stained cartilage images were obtained from mice with OA induced by medial meniscus instability. A total of 2,788 images from 1,000 knees of 520 mice were included for model development and evaluation. Each data set was evaluated using deep learning models with multiple selection criteria for the reference standard. For preprocessing, horizontal cartilage alignment was learned using a VGG16-based regression model, and the tibial cartilage region was detected using YOLO-v7. These learned weights were applied to generate a rotation- and crop-adjusted cartilage data set, which was used to evaluate three CNNs.Results Initial classification of 544 mice cartilage images showed low accuracy, leading to an expansion of the data set to 2,788 images. An algorithm was applied to align the images horizontally and crop only the joint region, thereby reducing misclassification of noncartilaginous regions. This approach significantly improved the accuracy of cartilage degradation scoring. Among the deep learning models evaluated, VGG16 showed the best performance, achieving an MAE of 0.33. The model also recorded a precision of 0.680 (95% CI: 0.668-0.693), recall of 0.645 (95% CI: 0.627-0.664), F1-score of 0.653 (95% CI: 0.636-0.671), and accuracy of 0.648 (95% CI: 0.631-0.665).Conclusion In this study, the VGG16 model showed high concordance with expert assessments, suggesting the feasibility of automating OA grading from histological images in large-scale animal studies.
Background Articular cartilage injuries often heal with fibrocartilage rather than native hyaline cartilage, resulting in inferior biomechanical properties and increased osteoarthritis risk. Curcumin has anti-inflammatory and antioxidant properties that may support cartilage repair; however, clinical use is limited by poor bioavailability. Micellar formulations enhance systemic absorption.Purpose To evaluate the effects of orally administered micellar curcumin on structural and molecular markers of osteochondral repair in a rat distal femoral defect model.Methods Thirty-two female Wistar rats were randomly allocated to 4 groups (n = 8 per group). Standardized 2-mm osteochondral defects were created in the distal femur. Animals received 250 mg/kg/day micellar curcumin or distilled water for 30 or 90 days. Macroscopic repair was assessed using the International Cartilage Repair Society (ICRS) scoring system. Histological evaluation followed ICRS guidelines and was performed in a blinded manner by 2 independent observers (intraclass correlation coefficient ICC = 0.89). Immunohistochemical analyses included SRY-box transcription factor 9 (SOX9), collagen type I (COL I), collagen type II (COL II), aggrecan, and matrix metalloproteinase-13 (MMP-13).Results Curcumin-treated groups demonstrated significantly higher macroscopic and histological scores than controls, particularly at 90 days. Increased expression of hyaline cartilage markers (SOX9, collagen II, aggrecan) and reduced collagen I expression were observed in treated groups. MMP-13 expression did not differ significantly between groups.Conclusion Oral micellar curcumin enhanced structural and molecular parameters of osteochondral repair in this preclinical model. Further translational and clinical studies are required before therapeutic application.
Background Knee osteoarthritis (KOA) is a prevalent cause of disability. Current intra-articular injections (hyaluronic acid [HA] and corticosteroids) fall short in maintaining long-term effects and repeated usage may result in deleterious effects on the knee. The development of hydrogels offers a potentially safe and longer-lasting alternative. Purpose To assess current literature and analyse the clinical outcomes of intra-articular hydrogel in patients with KOA. Methods A systematic search on 4 databases was performed in accordance with the Preferred Reporting Items for Systematic reviews and Meta‑Analyses. Quantitative findings were complemented by narrative synthesis. Study quality was assessed using the Cochrane Risk of Bias (RoB) 2.0 tool and Methodological Index for Non-Randomized Studies guidelines. Results Twelve studies comprising 1,413 patients were included. Most reported improvements in clinical outcomes above the minimal clinically important difference. Average follow-up was 11 months. Quality assessment revealed high risk of bias for randomized controlled trials (RCTs) ( n = 4) and low to moderate risk of bias non-randomized studies ( n = 8). Conclusion Intra-articular hydrogel injections for KOA represent an area of ongoing investigation. Current literature is heterogeneous and limited by methodological shortcomings. Adequately powered RCTs with standardized outcome reporting are needed to clarify their role in routine clinical practice. Level of evidence: Level II
