Triamcinolone acetonide reduces viability, induces oxidative stress, and alters gene expressions of human chondrocytes.

OBJECTIVE: Patients with knee osteoarthritis (OA) are sometimes prescribed intra-articular injections of glucocorticoids (GCs), such as triamcinolone acetonide (TA). Whether GCs cause chondrotoxicity is not known. We wished to ascertain if TA induces toxicity by causing oxidative stress and alters expression of P21, growth differentiation factor (GDF)15, and cFos. PATIENTS AND METHODS: Primary chondrocytes isolated from 10 OA patients undergoing total knee replacement surgery were incubated with TA (0, 1, 5, 10 mg/ml), with or without 100 µM vitamin C for 7 and 14 days for viability assays and 48 h for oxidative stress and gene expression analyses. RESULTS: TA significantly decreased chondrocyte viability and increased the ratio of oxidized glutathione to total glutathione suggesting an increase in oxidative stress. Vitamin C significantly increased the viability and decreased the oxidative stress of cells treated with 5 mg/ml TA. Expression of P21, GDF15, and cFos increased significantly when TA was added (5.17 ± 2.4-, 4.96 ± 3.1-fold for P21, 9.97 ± 2.9- and 4.2 ± 1.6-fold for GDF15, and 6.65 ± 4.8-, 12.96 ± 8.3-fold for cFos at 1, and 5 mg/ml TA, respectively). CONCLUSIONS: TA induced chondrotoxicity by increasing oxidative stress and altering expressions of genes involved in cell death. The addition of vitamin C decreased oxidative stress and increased viability, suggesting that antioxidants might attenuate TA toxicity in cartilage.

Effects of renal function on the intraosseous concentration and inhibitory effect of prophylactic cefazolin in knee arthroplasty.

OBJECTIVE: To compare intraosseous concentrations and inhibitory effects on the growth of Staphylococcus aureus following intravenous administration of 1 or 2 g of the prophylactic cefazolin between patients with decreased renal function vs. intact renal function undergoing total knee arthroplasty. PATIENTS AND METHODS: Ten patients (13 knees) with primary knee osteoarthritis were divided into two groups by creatinine clearance (CrCl) level (intact renal function: CrCl ≥75 mg/mL (four knees); decreased renal function: CrCl <75 mg/mL (nine knees)). Subchondral bone samples (proximal tibia and distal femur) were obtained during the procedure and were analyzed for the intraosseous concentration of cefazolin and the inhibitory effects on the growth of S. aureus using high-performance liquid chromatography and agar disc diffusion bioassays. RESULTS: Different levels of renal function showed no significant associations with mean intraosseous concentration and mean inhibitory effects at the proximal tibia and distal femur in patients administered 1 g cefazolin (p>0.05). For patients administered 2 g cefazolin, mean intraosseous concentration in the decreased renal function group was significantly higher at the proximal tibia (p=0.049) and also higher (but not reaching statistical significance) at the distal femur (p=0.073) compared with the intact renal function group. Mean inhibitory effects in the decreased renal function group were significantly lower than the intact renal function group at the proximal tibia (p=0.003) and distal femur (p=0.003). CONCLUSIONS: Deceased renal function played a role in the increased intraosseous concentration and decreased inhibitory effects in the groups receiving 2 g cefazolin. An excessive intraosseous concentration showed a negative influence on inhibitory effects on the growth of Staphylococcus aureus.

ADAMTS14 gene polymorphism associated with knee osteoarthritis in Thai women.

Osteoarthritis (OA) is the most prevalent form of arthritis in the elderly. This disease is characterized by breakdown and loss of articular cartilage due to genetic, mechanical and environmental factors. Although the pathophysiology of OA is not completely known, several candidate genes have been reported to be associated with OA susceptibility. We assessed the association between genetic variation in the ADAMTS14 region and knee osteoarthritis susceptibility in the Thai population. The rs4747096 SNP was genotyped by PCR-RFLP on genomic DNA extracted from peripheral blood of 108 OA patients and 119 controls. The PCR product (196 bp) was digested with BspEI. A sample with the GG genotype showed two band sizes of 158 and 38 bp, while a sample with the AA genotype showed a single band size of 196 bp. Heterozygotes with the AG genotype showed all three corresponding bands. Genotype distributions, allele frequencies and model of inheritance in patients and controls were compared. In females, the frequency of the AA genotype and the A allele were significantly higher in knee OA patients than in controls [odds ratio (OR) = 2.79, 95% confidence interval (CI) = 1.05-7.59 and OR = 1.58, 95%CI = 1.00-2.45, respectively]. Moreover, genotypic AA and AG were associated with significantly increased risk for knee OA when compared to GG (OR = 2.72, 95%CI = 1.10-6.87). No significant associations were observed in males. In conclusion, the nsSNP rs4747096 in ADAMTS14 was associated with knee OA in female Thai patients; therefore, the role of ADAMTS14 in OA seems to be gender-dependent.