Effect of 1,25-(OH)2D3 on Proliferation of Fibroblast-Like Synoviocytes and Expressions of Pro-Inflammatory Cytokines through Regulating MicroRNA-22 in a Rat Model of Rheumatoid Arthritis.

OBJECTIVE: This study aims to investigate the regulatory mechanism of 1,25-(OH)2D3 on the proliferation of fibroblast-like synoviocytes (FLS) and expressions of pro-inflammatory cytokines in rheumatoid arthritis (RA) rats via microRNA-22 (miR-22). METHODS: A rat model of RA was established with a subcutaneous injection of type II collagen. After treated with different concentrations of 1,25-(OH)2D3 the proliferation of FLS was estimated by the MTT method, and the optimal concentration of 1,25-(OH)2D3 was selected for further experiments. Cell proliferation was detected by MTT. Cell cycle and apoptosis were analyzed by FCM. The IL-1ß, IL-6, IL-8, and PGE2 protein expressions were determined by ELISA, and MMP-3, INOS, and Cox-2 mRNA expressions were measured by qRT-PCR. RESULTS: The rat model of RA was successfully established. Compared with the blank group, the 1,25-(OH)2D3 and miR-22 inhibitors groups exhibited higher proliferation inhibition and apoptosis rates, lower levels of pro-inflammatory cytokines (IL-1ß, IL-6, IL-8, and PGE2), and decreased mRNA expressions of MMP-3, INOS, and Cox-2. The miR-22 mimics group had lower proliferation inhibition and apoptosis rates, elevated expressions of pro-inflammatory cytokines and MMP-3, INOS, and Cox-2 than the blank group. In contrast to the 1,25-(OH)2D3 group, the proliferation inhibition and apoptosis rates were down-regulated, and the expressions of pro-inflammatory cytokines and MMP-3, INOS, and Cox-2 were up-regulated in the 1,25-(OH)2D3 + miR-22 mimics group. CONCLUSION: Our study demonstrated that 1,25-(OH)2D3 inhibits the proliferation of FLS and alleviates inflammatory response in RA rats by down-regulating miR-22.

Correlates of Hip Cartilage Defects: A Cross-sectional Study in Older Adults.

OBJECTIVE: Knee cartilage defects are a key feature of osteoarthritis (OA) but correlates of hip defects remain unexplored. The aims of this cross-sectional study were to describe the correlates of hip cartilage defects. METHODS: The study included 194 subjects from the Tasmanian Older Adult Cohort who had right hip short-tau inversion recovery magnetic resonance imaging (MRI). Hip cartilage defects were assessed and categorized as grade 0 = no defects, grade 1 = focal blistering or irregularities on cartilage or partial thickness defect, and grade 2 = full thickness defect. Hip pain was determined by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Hip structural changes were measured on MRI, and hip radiographic OA (ROA) was assessed. Leg strength and physical activity were assessed using dynamometer and pedometers, respectively. Data were analyzed using log binomial and linear regression. RESULTS: Of 194 subjects, 24% (n = 48) had no defects, 34% (n = 66) had grade 1, and 41% (n = 80) had grade 2. In multivariable analyses, any hip defects were associated with greater hip pain [prevalence ratio (PR) 1.20, 95% CI 1.02-1.35] and lower mean leg strength (men; mean ratio 0.83, 95% CI 0.67-0.98). Grade 1 defects were associated with hip bone marrow lesions (BML; PR 1.42, 95% CI 1.03-1.96) and high cartilage signal (men; PR 1.84, 95% CI 1.27-2.70), but not with hip pain or other structural findings. Grade 2 defects were associated with greater hip pain (PR 1.40, 95% CI 1.09-1.80), hip BML (PR 1.45, 95% CI 1.15-1.85), hip effusion cross-sectional area (PR 1.14, 95% CI 1.01-1.30), hip ROA (men; PR 1.60, 95% CI 1.13-2.25), and steps/day (PR 0.97, 95% CI 0.96-0.99). CONCLUSION: Grade 2 defects in both sexes and grade 1 defects (mostly in men) are associated with clinical, demographic, and structural factors relevant for OA. Damage to the hip cartilage could be one of the major causes of rapid disease progression and pathophysiology of hip defects. The topic needs further study.

Change in knee structure and change in tibiofemoral joint space width: a five year longitudinal population-based study.

BACKGROUND: Change in knee cartilage volume is frequently used as a proxy for change in knee joint space width over time, but longitudinal data on these associations is limited. We aimed to determine whether change in knee cartilage volume, new or worsening meniscal extrusion (ME), meniscal tears and cartilage defects over 2.4 years correlated with change in joint space width (JSW) over 5 years in older community dwelling adults. METHODS: Participants (n = 153) had their right knee imaged using MR imaging and x-ray at baseline, and after 2.4 years (MRI) and 5 years (x-ray). Cartilage volume, cartilage defects, meniscal extrusions and meniscal tears were assessed on sagittal T1-weighted fat-suppressed MRI. JSW was assessed using standard fixed semi-flexed view radiographs, and scored on those with adequate alignment. RESULTS: Participants were 51-79 (mean 62) years old; 48% were female. Cartilage volume reduced over time (medial -134 ± 202 µL/year, lateral -106 ± 165 µL/year, p < 0.001), as did JSW (medial -0.05 ± 0.16 mm/year, lateral -0.12 ± 0.24 mm/year, p < 0.001). In multivariable analysis, the only consistent predictor of change in JSW was new or worsening ME (medial tibia R(2) 3.1%, p = 0.031; medial femur R(2) 3.2%, p = 0.024); change in cartilage volume correlated with change in JSW laterally (R(2) 4.8%, p = 0.007) and was borderline medially (R(2) 2.2%, p = 0.064); there was no association for meniscal tears or cartilage defects. The magnitude of these associations were similar albeit somewhat greater for ME in participants with radiographic OA (R(2) 6.2%, p = 0.017). CONCLUSION: Change in ME and cartilage volume weakly predict change in JSW, but the vast majority of the variation remains unexplained. Since MRI examines cartilage directly while radiographs examine it indirectly, these results cast doubt on the validity of using JSW as a proxy measure of cartilage loss.