CARTILAGE最新文献

Objective: Chronic inflammation plays an important role in the osteoarthritis (OA) pathology but how this influence OA disease progression is unclear. Leukotriene B4 (LTB₄) is a potent proinflammatory lipid mediator generated from arachidonic acid through the sequential activities of 5-lipoxygenase, 5-lipoxygenase-activating protein, Leukotriene A₄ hydrolase (LTA₄H) and its downstream product LTB₄. The aim of this study is to investigate the involvement and the potential therapeutic target of the LTB₄ pathway in OA disease progression.

Design: Both clinical human cartilage samples (n = 7) and mice experimental OA models (n = 6) were used. The levels of LTA₄H and leukotriene B4 receptor 1 were first examined using immunostaining in human OA/non-OA cartilage and mice experimental OA models. We also determined whether the LTA₄H pathway was associated with cartilage degeneration and synovitis inflammation in OA mice models and human articular chondrocytes.

Results: We found that both LTA₄H and LTB₄ receptor (BLT1) were highly expressed in human and mice OA cartilage. Inhibition of LTA₄H suppressed cartilage degeneration and synovitis in OA mice model. Furthermore, inhibition of LTA₄H promoted cartilage regeneration by upregulating chondrogenic genes expression such as aggrecan (ACAN), collagen 2A1 (COL2A1), and SRY-Box transcription factor 9 (SOX9).

Conclusions: Our results indicate that the LTA₄H pathway is a crucial regulator of OA pathogenesis and suggest that LTA₄H could be a therapeutic target in combat OA.

Objective: Fibrin sealants are routinely used for intra-articular surgical fixation of cartilage fragments and implants. However, the mechanical properties of fibrin sealants in the context of cartilage repair are unknown. The purpose of this study was to characterize the adhesive and frictional properties of fibrin sealants using an ex vivo model.

Design: Native bovine cartilage-bone composites were assembled with a single application of Tisseel or Vistaseal. Composites were tested in tension and lap shear. In addition, the coefficient of friction (COF) was measured in a native cartilage annulus model alone and with minced cartilage. Finally, the effect of a double application of fibrin sealant was evaluated.

Results: There were no significant differences in tensile modulus, ultimate tensile strength (UTS), shear modulus, or ultimate shear strength (USS) between the 2 fibrin sealants. Both fibrin sealants demonstrated a UTS and USS of <8 and <30 kPa, respectively. There were no differences in COF between the sealants when tested alone or with minced cartilage. A double application of fibrin sealant did not alter the mechanical properties compared with a single application of fibrin sealant.

Conclusions: Fibrin sealant adhesive properties are not affected by the sealant type studied or the number of applications in a bovine cartilage-bone model. Fibrin sealant tribological properties are not affected by sealant type or the addition of minced cartilage. The adhesive properties of Tisseel and Vistaseal were less than those desired for the in vivo fixation of cartilage repair implants. These findings motivate the development of an improved cartilage-specific adhesive for cartilage repair applications.

Objective: Knee osteoarthritis (KOA) is a complex degenerative joint disease and a major cause of joint dysfunction. This study aimed to explore the function of hsa_circ_0007482 on inflammation, proliferation, differentiation, and apoptosis in KOA.

Design: Real-time quantitative polymerase chain reaction (PCR) was performed to detect the expression of circ_0007482, inflammatory factors, and differentiation-related molecules in KOA chondrocytes and interleukin (IL)-1β-stimulated chondrocytes. The correlation between the circ_0007482 expression and inflammatory factors was analyzed by the Pearson method. KOA cell model was established using IL-1β for 24 hours. The proliferation activity of chondrocytes was evaluated by CCK-8 assay, and cell apoptosis rate was assessed by flow cytometry. The downstream miRNA of circ_0007482 was validated using dual-luciferase reporter assay.

Results: The circ_0007482 expression was elevated in both KOA cartilage tissues and IL-1β-treated chondrocytes and positively correlated with inflammatory factors expression. In comparison to the control group, IL-1β treatment diminished chondrocyte proliferation abilities and increased cell apoptosis and inflammatory factors IL-6, IL-8, and tumor necrosis factor (TNF)-α mRNA expression. Inhibition of circ_0007482 partially improved IL-1β-induced inflammatory reaction. Circ_0007482 could negatively regulate the expression of miR-558.

Conclusions: Interfering of circ_0007482 might partially promote cell proliferation and differentiation, while inhibit cell apoptosis to improve joint injury by regulating miR-558 in IL-1β-treated chondrocyte cell model.

Objective: To 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).

Design: In 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.

Results: Compared 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.

Conclusions: Higher 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.

Objective: Hyaluronic acid (HA) in synovial fluid (SF) contributes to boundary lubrication with altered levels in osteoarthritis (OA) and rheumatoid arthritis (RA). SF extracellular vesicles (EVs) may participate in arthritis by affecting inflammation and cartilage degradation. It remains unknown whether HA and EVs display joint-specific alterations in arthritic SFs.

Design: We investigated the numbers and characteristics of HA-particles and large EVs in SF from knees and shoulders of 8 OA and 8 RA patients and 8 trauma controls, and in plasma from 10 healthy controls and 11 knee OA patients. The plasma and SF HA concentrations were determined with a sandwich-type enzyme-linked sorbent assay, and EVs and HA-particles were characterized from plasma and unprocessed and centrifuged SFs with confocal microscopy. The data were compared according to diagnosis, location, and preanalytical processing.

Results: The main findings were: (1) OA and RA SFs can be distinguished from trauma joints based on the distinctive profiles of HA-particles and large EVs, (2) there are differences in the SF HA and EV characteristics between shoulder and knee joints that could reflect their dissimilar mobility, weight-bearing, and shock absorption properties, (3) EV counts in SF and plasma can positively associate with pain parameters independent of age and body adiposity, and (4) low-speed centrifugation causes alterations in the features of HA-particles and EVs, complicating their examination in the original state.

Conclusions: Arthritis and anatomical location can affect the characteristics of HA-particles and large EVs that may have potential as biomarkers and effectors in joint degradation and pain.