CARTILAGE最新文献

ObjectiveThis study aimed to compare short-term arthroscopic and clinical outcomes between microfractures with (treatment group) and without (control group) acellular particulated costal allocartilage in patients undergoing concurrent high tibial osteotomy (HTO).DesignThis retrospective cohort study enrolled 19 and 21 patients in the treatment and control groups, respectively, and reviewed them at a minimum 2-year follow-up after HTO. Cartilage regeneration status was evaluated according to the International Cartilage Repair Society-Cartilage Repair Assessment (ICRS-CRA) grading and Koshino's macroscopic staging systems during medial locked plate removal. Patient-reported measures, including the visual analog scale pain score, Knee Injury and Osteoarthritis Outcome Score, and International Knee Documentation Committee score, assessed clinical outcomes.ResultsThe total points of the ICRS-CRA grading system were significantly higher in the treatment group than in the control group (7.7 ± 3.8 vs 4.2 ± 3.0, respectively; P = 0.007). Likewise, the cartilage status according to Koshino's macroscopic staging system was better in the treatment group (P = 0.022). Patient-reported functional outcomes significantly improved postoperatively but were equivalent between the study groups at the final follow-up.ConclusionsMicrofractures augmented with acellular particulated costal allocartilage resulted in better repair quality than microfractures alone at a minimum 2-year follow-up after HTO, but functional outcomes improved similarly for both treatment approaches.

ObjectiveTo investigate the effect of higher cumulative defined daily dose per year (cDDD/y) compared with lower cDDD/y of statin use in the incidence of any joint osteoarthritis (OA).DesignIn this population-based retrospective cohort study, patients who were aged ≥40 years were newly initiated on statin therapy between 2002 and 2011, and had a statin prescription for ≥90 days in the first year of treatment were identified from the 2000 Longitudinal Generation Tracking Database. All patients were separated into groups with higher cDDD/y (>120 cDDD/y) and lower cDDD/y (≤120 cDDD/y; as an active comparator) values. Propensity score matching was performed to balance potential confounders. All recruited patients were followed up for 8 years. Marginal Cox proportional hazard models were used to estimate time-to-event outcomes of OA.ResultsCompared with lower cDDD/y use, higher cDDD/y use did not reduce the risk of any joint OA (adjusted hazard ratio, 1.07; 95% confidence interval, 0.99-1.14). Dose-related analysis did not reveal any dose-dependent association. A series of sensitivity analyses showed similar results. Joint-specific analyses revealed that statin did not reduce the incidence of knee, hand, hip, and weight-bearing (knee or hip) OA.ConclusionsHigher cDDD/y statin use did not reduce the risk of OA in this Taiwanese nationwide cohort study. The complexity of OA pathogenesis might contribute to the ineffectiveness of statin. Repurposing statin with its anti-inflammation properties might be ineffective for OA development, and balancing the catabolism and anabolism of cartilage might be a major strategy for OA prevention.

ObjectiveOur study was performed to investigate whether micro-223 promotes diabetic Osteoarthritis (OA) progression by regulating cartilage degeneration and subchondral bone remodeling.MethodsThe expression of miR-223 in human normal cartilage, OA cartilage, and subchondral bone tissue with or without DM was detected by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). miR-223 mimic or inhibitor was transfected into chondrocytes. Cell viability and apoptosis were assessed by 3-(4,5)-dimethylthiahiazo(-2)-3,5-diphenyltetrazolium bromide (MTT) and Terminal Deoxynucleotidyl Transferase(TdT)-mediated dUTP nick end labeling (TUNEL) assay, respectively.ResultsmiR-223 was significantly higher in human diabetic OA cartilage and subchondral bone compared with normal OA and healthy control. Overexpression of miR-223 accelerated cartilage degeneration and subchondral bone sclerosis in diabetic OA mice, whereas miR-223 inhibition had the opposite effect. In vitro upregulation of miR-223 decreased proliferation and enhanced apoptosis of chondrocytes. Meanwhile, downregulation of miR-223 promoted glycosaminoglycan (GAG) production in chondrocytes.ConclusionmiR-223 promotes diabetic OA progression by regulating cartilage degeneration and subchondral bone remodeling both in vitro and in vivo.

ObjectiveThe use of porcine animal models for cartilage injury has increased recently due to their similarity with humans with regard to cartilage thickness, limited intrinsic healing of chondral defects, and joint loading biomechanics. However, variations in the mechanical and biochemical properties of porcine hip articular cartilage among various tissue ages and weightbearing (WB) regions are still unknown. This study's aim was to characterize the mechanical and biochemical properties of porcine hip articular cartilage across various ages and WB regions.MethodsArticular cartilage explants were harvested from WB and non-weightbearing (NWB) surfaces of the femoral head and acetabulum of domesticated pigs (Sus scrofa domesticus) at fetal (gestational age: 80 days), juvenile (6 months), and adult (2 years) ages. Explants underwent compressive stress-relaxation mechanical testing, biochemical analysis for total collagen and glycosaminoglycan (GAG) content, and histological staining.ResultsJuvenile animals consistently had the highest mechanical properties, with 2.2- to 7.6-time increases in relaxation modulus, 1.3- to 2.3-time increases in instantaneous modulus, and 4.1- to 14.2-time increases in viscosity compared with fetal cartilage. Mechanical properties did not significantly differ between the WB and NWB regions. Collagen content was highest in the NWB regions of the juvenile acetabulum (65.3%/dry weight [DW]) and femoral head (75.4%/DW) cartilages. GAG content was highest in the WB region of the juvenile acetabulum (23.7%/DW) and the WB region of the fetal femoral head (27.5%/DW) cartilages. Histological staining for GAG and total collagen content followed the trends from the quantitative biochemical assays.ConclusionThis study provides a benchmark for the development and validation of preclinical porcine models for hip cartilage pathologies.

ObjectiveThe superficial zone (SZ) of articular cartilage is responsible for distributing shear forces for optimal cartilage loading and contributes to joint lubrication through the production of proteoglycan 4 (PRG4). PRG4 plays a critical role in joint homeostasis and is chondroprotective. Normal PRG4 production is affected by inflammation and irregular mechanical loading in post-traumatic osteoarthritis (PTOA). THe SZ chondrocyte (SZC) phenotype, including PRG4 expression, is regulated by the actin cytoskeleton in vitro. There remains a limited understanding of the regulation of PRG4 by the actin cytoskeleton in native articular chondrocytes. The filamentous (F)-actin cytoskeleton is a potential node in crosstalk between mechanical stimulation and cytokine activation and the regulation of PRG4 in SZCs, therefore developing insights in the regulation of PRG4 by actin may identify molecular targets for novel PTOA therapies.Materials and methodsA comprehensive literature search on PRG4 and the regulation of the SZC phenotype by actin organization was performed.ResultsPRG4 is strongly regulated by the actin cytoskeleton in isolated SZCs in vitro. Biochemical and mechanical stimuli have been characterized to regulate PRG4 and may converge upon actin cytoskeleton signaling.ConclusionActin-based regulation of PRG4 in native SZCs is not fully understood and requires further elucidation. Understanding the regulation of PRG4 by actin in SZCs requires an in vivo context to further potential of leveraging actin arrangement to arthritic therapeutics.

ObjectiveTo assess whether change of semiquantitatively magnetic resonance imaging (MRI)-defined bone marrow lesions (BMLs) and inflammatory markers is associated with change in quantitatively-assessed cartilage loss in the femorotibial joint (FTJ) in knees with radiographic osteoarthritis (OA) over 24 months.DesignParticipants were included from the IMI-APPROACH and the Osteoarthritis Initiative FNIH studies. Semiquantitative MRI assessment was performed for BMLs, Hoffa- and effusion-synovitis. Quantitative cartilage thickness measurements were performed manually. Definitions of change included number of subregions with BMLs, change in sum and change in maximum increase in size. Change in Hoffa-synovitis and effusion-synovitis was categorized in addition. Between-group comparisons regarding cartilage loss in the FTJ, medial and lateral compartments were performed using analysis of variance (ANOVA).ResultsA total of 629 participants were included. Knees without any BMLs at baseline (BL) and follow-up (FU) had significantly less cartilage loss compared to the other subgroups. Change in both directions in the sum score of BMLs was associated with increased rates of cartilage loss. Maximum increase in size of BMLs was associated with increased rates of cartilage loss (FTJ increase by 2 grades -0.183 mm, 95% CI [-0.335, -0.031], by 3 grades -0.306 mm, [-0.511, -0.101]). Worsening of Hoffa-synovitis was associated with increased rates of cartilage loss.ConclusionKnees without BMLs at BL and FU showed lowest rates of cartilage loss. Knees with an increase in BML size showed increased rates of concurrent cartilage loss. Approaches with the aim to inhibit BML development, avoidance of increase in size and avoidance of Hoffa-synovitis worsening may have beneficial effects on cartilage loss.

BackgroundCell-based therapies to regenerate native-like cartilage are limited by the inability to re-express zone-specific molecules. While monolayer-expanded (passaged) chondrocytes are a clinically approved cell source, the resulting tissues have reduced Proteoglycan-4 (PRG4) expression. This may be due to poor attachment, slow proliferation, and dedifferentiation of superficial zone chondrocytes (SZC) on polystyrene. Optimizing expansion conditions is therefore critical. Chondrocyte-derived decellularized extracellular matrix (CD-ECM) has been shown to enhance proliferation and reduce dedifferentiation of full-thickness chondrocytes, but its effect on SZC remains unknown. We tested the hypothesis that culturing SZC on CD-ECM would improve attachment, proliferation, and reduced dedifferentiation, enabling formation of PRG4-expressing tissue.MethodsPrimary bovine SZC were seeded on polystyrene or CD-ECM. Attachment, expansion rate, and gene expression were evaluated during passaging. Cells from each condition were assessed for their capacity to form PRG4-expressing bioengineered tissue.ResultsPrimary bovine SZC had increased attachment and reached confluency faster on CD-ECM. SZC on CD-ECM were smaller, with fewer actin stress fibers, and exhibited reduced expression of dedifferentiation markers. Furthermore, SZC expanded on CD-ECM were stimulated to form tissues rich in Collagen II and Aggrecan with higher Proteoglycan-4 expression.ConclusionsThe use of CD-ECM for passaging SZC may aid in achieving an adequate number of SZC for bioengineering purposes.

ObjectiveBiofluid amino acids (AAs) are potential biomarkers and therapeutic targets for knee osteoarthritis (KOA), a disease continuum of both mechanical and inflammatory aspects. Our aim was to identify AAs that would associate with cartilage degradation, subjectively and objectively assessed joint pain and function, and psychological well-being.DesignFasting blood was sampled from 8 healthy controls at baseline, and from 8 end-stage KOA patients before total knee arthroplasty and 1 year post-operatively. Plasma AA profiles were determined with high-performance liquid chromatography, and the obtained results were analyzed with univariate and multivariate statistical tests, and with pathway analysis by MetaboAnalyst.ResultsCystine, β-alanine, and hydroxylysine emerged as potential biomarkers distinguishing KOA patients from controls, and several metabolic pathways were disturbed in baseline KOA. Total knee arthroplasty reduced pain and improved joint function, but the effects on plasma AA metabolism were less obvious. There were significant associations between systemic AA levels and articular cartilage thickness, KOA pain, physical performance, corticospinal excitability, and mental health, independent of age and body adiposity.ConclusionThe results suggest that AA metabolism could play a role in KOA pathophysiology and motivate further studies investigating the potential of AAs as diagnostic biomarkers and therapeutic targets.

ObjectivesCartilage repair (CR) surgery and anterior cruciate ligament reconstruction (ACL-R) are common joint procedures, particularly in younger patients. However, the impact of prior or concurrent ACL-R on the outcomes of CR remains uncertain. This study aimed to evaluate whether ACL-R affects the structural quality and clinical outcomes of CR tissue.MethodsIn this retrospective multicenter study, 71 patients undergoing CR were followed up with magnetic resonance imaging (MRI) and clinical evaluations at 3, 12, and 60 months. Of these, 22 patients underwent ACL-R before or during CR. Morphological assessment was performed using Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) 2.0 scores; compositional analysis included T2 mapping (n = 45). Patient-reported outcome measures (PROM) were assessed at all time points. Statistical tests included the Mann-Whitney U-test, Wilcoxon signed-rank test, and simulation-based power analysis.ResultsMOCART 2.0 scores and T2 mapping values showed no significant group differences at any time point. Both groups demonstrated significant improvements in PROMs from baseline to 60 months. However, at 60 months, the ACL-R group had significantly lower PROMs than the non-ACL-R group.ConclusionAlthough long-term clinical outcomes were worse in patients with ACL-R, all PROMs improved significantly from baseline to 60 months in both groups. MRI showed no significant differences in focal CR tissue quality, suggesting structural success regardless of ACL-R. While ACL-R patients remain at higher risk of joint degeneration, they can still experience mid-term clinical benefit from CR. These findings support its use in ACL-R patients when joint function is properly restored and expectations are managed.