TRIM52 knockdown inhibits proliferation, inflammatory responses and oxidative stress in IL-1ß-induced synovial fibroblasts to alleviate temporomandibular joint osteoarthritis.

To explore the mechanism of tripartite motif 52 (TRIM52) in the progression of temporomandibular joint osteoarthritis (TMJOA). Gene and protein expression were tested by quantitative real-time polymerase chain reaction and western blot, respectively. The levels of pro-inflammatory cytokines and oxidative stress factors were evaluated using enzyme-linked immunosorbent assay and biochemical kit, respectively. Cell counting kit-8 and 5-ethynyl-2'-deoxyuridine assays were carried out to assess cell proliferation. Immunofluorescence was used to detect the expression of CD68 and Vimentin in primary synovial fibroblasts (SFs). Haematoxylin and eosin staining and Safranin O/Fast green were used to evaluate the pathological damage of synovial and cartilage tissue in rats. TRIM52 was upregulated in the synovial tissue and SFs in patients with TMJOA. Interleukin (IL)-1ß treatment upregulated TRIM52 expression in TMJOA SFs and normal SF (NSF), promoting cell proliferation, inflammatory response and oxidative stress in NSF, SFs. Silence of TRIM52 relieved the cell proliferation, inflammatory response and oxidative stress induced by IL-1ß in SFs, while overexpression of TRIM52 enhanced IL-1ß induction. Meanwhile, IL-1ß induction activated toll-like receptor 4 (TLR4)/nuclear factor (NF)-κB pathway, which was augmented by upregulation of TRIM52 in NSF, and was attenuated by TRIM52 knockdown in SFs. Besides, pyrrolidinedithiocarbamic acid ameliorated IL-1ß-induced proliferation and inflammatory response by inhibiting TLR4/NF-κB signalling. Meanwhile, TRIM52 knockdown inhibited cell proliferation, oxidative stress and inflammatory response in IL-1ß-induced SFs through downregulation of TLR4. TRIM52 promoted cell proliferation, inflammatory response, and oxidative stress in IL-1ß-induced SFs. The above functions were mediated by the activation of TLR4/NF- κB signal pathway.

Variants at potential loci associated with Sjogren's syndrome in Koreans: A genetic association study.

Sjogren's syndrome (SS), a chronic autoimmune disease, typically causes or involves inflammation in the salivary and lacrimal glands. Although recent genetic association studies have contributed to the discovery of SS susceptible genes, few studies have reported on the Korean population. Here, we did a genetic association study of SS in Korean patients using whole-exome sequencing data of 15 patients and 100 healthy controls. In addition to confirming previously described SS susceptibility loci MSH5 (p = 1.67 × 10-5) and RELN (p = 4.91 × 10-6), we also validated PRAMEF13 (p = 2.28 × 10-5), TARBP1 (p = 1.87 × 10-5), UGT2B28 (p = 1.33 × 10-5), TRBV5-6 (p = 2.27 × 10-5) and NAPB (p = 3.73 × 10-5) as novel susceptibility loci for SS. Furthermore, we identified UGT2B28, TARBP1 and PRAMEF13 as associated with human immune function. These findings may provide useful insight into to the pathways and pathogenesis contributing to SS susceptibility in the Korean population.

Bergapten exerts a chondroprotective effect in temporomandibular joint osteoarthritis by combining intestinal flora alteration and reactive oxygen species reduction.

Bergapten, a furanocoumarin naturally occurring in bergamot essential oil, has been demonstrated to have the potential to alleviate osteoarthritis-related symptoms via its anti-inflammatory activity. Although its systemic bioavailability is limited, its precise mechanisms of action and effects on temporomandibular joint osteoarthritis (TMJOA) and its relationship with the intestinal flora remain unclear. Here, we explored the anti-TMJOA effect of BGT combined with the interleukin-1ß-induced inflammatory response of chondrocytes in a monosodium iodoacetate (MIA)-induced TMJOA rat model. It was confirmed that BGT effectively reduced proinflammatory mediators and increased type II collagen, bone volume, and trabecular number of condyles in TMJOA rats. Importantly, the oral administration of BGT altered the intestinal flora of rats by increasing the relative abundances of nine prebiotic species and decreasing the relative abundance of one potential species. In addition, BGT considerably reduced reactive oxygen species (ROS) levels by suppressing glutathione, oxidized glutathione, and superoxide dismutase in the serum and malondialdehyde in urine. These results suggest that BGT exerts a chondroprotective effect, most likely by improving the intestinal flora and reducing ROS production associated with TMJOA in rats. This finding indicates a novel beneficial effect of BGT on the prevention and treatment of TMJOA.