Interleukin-6 In Chondrocytes Research Articles

Transient Receptor Potential Ankyrin 1 (TRPA1) Is Involved in Upregulating Interleukin-6 Expression in Osteoarthritic Chondrocyte Models.

Transient receptor potential ankyrin 1 (TRPA1) is a membrane-bound ion channel found in neurons, where it mediates nociception and neurogenic inflammation. Recently, we have discovered that TRPA1 is also expressed in human osteoarthritic (OA) chondrocytes and downregulated by the anti-inflammatory drugs aurothiomalate and dexamethasone. We have also shown TRPA1 to mediate inflammation, pain, and cartilage degeneration in experimental osteoarthritis. In this study, we investigated the role of TRPA1 in joint inflammation, focusing on the pro-inflammatory cytokine interleukin-6 (IL-6). We utilized cartilage/chondrocytes from wild-type (WT) and TRPA1 knockout (KO) mice, along with primary chondrocytes from OA patients. The results show that TRPA1 regulates the synthesis of the OA-driving inflammatory cytokine IL-6 in chondrocytes. IL-6 was highly expressed in WT chondrocytes, and its expression, along with the expression of IL-6 family cytokines leukemia inhibitory factor (LIF) and IL-11, were significantly downregulated by TRPA1 deficiency. Furthermore, treatment with the TRPA1 antagonist significantly downregulated the expression of IL-6 in chondrocytes from WT mice and OA patients. The results suggest that TRPA1 is involved in the upregulation of IL-6 production in chondrocytes. These findings together with previous results on the expression and functions of TRPA1 in cellular and animal models point to the role of TRPA1 as a potential mediator and novel drug target in osteoarthritis.

MiR-27a alleviates osteoarthritis in rabbits via inhibiting inflammation.

To investigate the regulatory effect of micro ribonucleic acid-27a (miR-27a) on the nuclear factor-kappa B (NF-κB) pathway and to explore its effect on rabbits with osteoarthritis (OA). Anterior cruciate ligament (ACL) cross-section method was adopted to establish OA rabbit models. Cartilage specimens were collected to detect expression levels of miR-27a in OA cartilage and normal cartilage tissues. Meanwhile, chondrocytes were isolated and cultured, and transfected with miR-27a mimics and miR-27a inhibitor. Blank control group was set up. Next, the changes in chondrocyte proliferation were detected using 5-ethynyl-2'-deoxyuridine (EdU) staining and cell counting kit-8 (CCK-8). Quantitative Real Time Polymerase Chain Reaction (PCR) was applied to detect the messenger RNA (mRNA) expression of inflammatory factors interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) in chondrocytes. Also, Western blot was adopted to detect the differential expression of NF-κB pathway-related proteins NF-κB and matrix metalloproteinase 13 (MMP-13). Compared with that in normal cartilage tissues, miR-27a in OA cartilage tissues was decreased evidently (p<0.05). The expression level of miR-27a was higher in miR-27a mimics group than in control group, while it significantly declined in miR-27a inhibitor group (p<0.05). EdU staining and CCK-8 method results showed that miR-27a mimics could promote the proliferation of chondrocytes, while miR-27a inhibitor inhibited the proliferation of chondrocytes. Compared with those in control group, the expression levels of inflammatory factors TNF-α and IL-6 in chondrocytes in miR-27a inhibitor group were increased significantly (p<0.05). MiR-27a mimics could evidently reduce the expression of inflammatory factor IL-6 (p<0.05), but did not significantly reduce the expression of TNF-α. Besides, the results of Western blot suggested that the expression levels of MMP-13 and NF-κB proteins were decreased significantly in miR-27a mimics group (p<0.05) and increased significantly in miR-27a inhibitor group (p<0.05). MiR-27a in OA cartilage tissues is evidently lower than in normal cartilage tissues. Transfection of miR-27a mimics can promote proliferation of chondrocytes, lower the expression of inflammatory factors, and reduce the expression of MMP-13 and NF-κB proteins. Therefore, the up-regulation of miR-27a can benefit the treatment of bone joints through the NF-κB pathway.

IL-6/STAT3 signalling blockade protects against experimental osteoarthritis in mice

IL-6/STAT3 signalling blockade protects against experimental osteoarthritis in mice