Chemerin is a chemokine found in adipose tissue that specifically binds to the G protein-coupled receptor, chemokine-like receptor 1, and acts as a chemoattractant for macrophages and dendritic cells. Chemerin levels in the synovial fluid are associated with disease severity in patients with osteoarthritis (OA). However, to the best of our knowledge, the specific mechanism through which chemerin exerts its effects in OA remains unclear. The present study aimed to investigate the underlying mechanism of chemerin-associated synoviocyte inflammation. A Cell Counting Kit-8 assay was used to determine the optimal concentration of chemerin that exerted an effect on the viability of normal rat synoviocytes. The expression levels of MEK/ERK signaling pathway-related marker genes, including MEK, ERK, MMP-3 and MMP-13, were detected using reverse transcription-quantitative PCR. In addition, chemerin-induced phosphorylation of MEK, ERK1/2 and p38 MAPK was analyzed using western blotting, and the production of inflammatory factors following chemerin treatment was determined using ELISA. For the in vivo assessment of the effect of chemerin, Sprague Dawley rats underwent knee surgery to establish an arthritis model. The knee joints were then injected with normal saline or recombinant chemerin, and the synovium and knee joint tissues were harvested for H&E histological observations after 3 weeks. In addition, synovial tissue was analyzed for the production of inflammatory factors by ELISA. The results of the present study revealed that chemerin enhanced the viability of synoviocytes in a dose-dependent manner. The stimulatory effect of chemerin on synoviocytes was shown to be accompanied by the activation of MEK, ERK1/2 and p38 MAPK, which was associated with the production of MMP-13, MMP-3, TNF-α, IL-6 and IL-1β by synoviocytes. Inhibition of the ERK1/2 signaling pathway significantly reduced chemerin-induced MMP-13, MMP-3, TNF-α, IL-6 and IL-1β production. H&E staining showed that synovial hyperplasia and articular cartilage wear were more severe in chemerin treated rats after knee surgery than in knee surgery alone and saline controls. In addition, the articular cartilage surface was damaged, and the synovial tissue showed inflammatory cell infiltration. In Sprague Dawley rats that underwent surgery, but did not receive chemerin treatment, a slight raise in inflammatory cell infiltration and increased levels of inflammatory factors were observed compared with rats that did not undergo surgery; however, Secretion of downstream inflammatory cytokines IL-6, MMP-3, MMP-13, and IL-1β was significantly increased in chemerin treated groups compared with control and chemerin + PD98059 groups. In conclusion, the findings of the present study suggested that chemerin may enhance the production of inflammatory factors in synoviocytes by activating the MEK/ERK signaling pathway.

Review question / Objective: (1) What are research findings on the relation between immersive technology and creativity in higher education? (2) Is immersive technology conductive to improving students’ creativity? (3) To what extent does immersive technology affect students’ creativity? (4) Are there significant differences in moderating variables such as type of intervention, subject, grade level, time, and team or individual? (5) What are future research directions regarding the educational use of immersive technology based on the reviewed literature? Condition being studied: Creativity is recognized as a crucial 21st-century skill, and immersive technology can stimulate students' creativity.

AimChemerin is a chemokine from adipose tissue that specifically binds to the G protein-coupled receptor ChemR23 and has a chemotactic effect on macrophages and dendritic cells. A correlation between chemerin levels in synovial fluid and disease severity has been demonstrated in patients with osteoarthritis. However, the specific mechanism by which chemerin exerts its effects on osteoarthritis remains unclear. In this study, we investigated the mechanism of chemerin-associated synoviocyte inflammation.MethodsCell Counting Kit-8 (CCK-8) assays were used to identify concentrations of chemerin that had an effect on normal rat synoviocytes. The expression changes of mitogen-activated protein kinase kinase (MEK)/extracellular regulated protein kinases (ERK) pathway marker genes, including MEK, ERK, matrix metalloproteinase (MMP)-3 and MMP-13, were detected by fluorescence quantitative polymerase chain reaction (PCR). The phosphorylation of MEK, ERK1/2 and p38 mitogen-activated protein kinases (p38MAPK) by chemerin was analyzed by Western blotting, and the production of inflammatory factors after chemerin treatment was determined by enzyme-linked immunosorbent assay (ELISA). For in vivo assessment of chemerin function, rats were subjected to knee operation to provide a model for arthritis. The knees were then injected with normal saline or recombinant chemerin, and three weeks later, the synovium and knee joint tissue were harvested for HE staining observation and the synovial tissue was harvested for ELISA.ResultsChemerin was demonstrated to enhance the proliferation of synoviocytes in a dose-dependent manner. The stimulatory effect of chemerin on synoviocytes was shown to involve the activation of MEK, ERK1/2 and p38, which was associated with the production of MMP-13, MMP-3, interleukin (IL)-6 and IL-1β by synoviocytes. Inhibition of the ERK1/2 signaling pathway significantly inhibited chemerin-induced MMP-13, MMP-3, IL-6 and IL-1β production. HE staining showed that the degree of synovial hyperplasia and articular cartilage abrasion was more severe in chemerin-treated rats after knee operation. The articular cartilage surface was damaged, and the synovial tissue showed inflammatory cell infiltration. In rats that underwent operation without chemerin treatment, there was a slight inflammatory infiltration and higher levels of inflammatory factors as compared to unoperated rats; however, secretion of the downstream inflammatory factors IL-6, matrix metalloproteinases (MMP-3 and MMP-13) and IL-1β was significantly greater in the drug-treated group (P<0.05).ConclusionChemerin enhances the production of inflammatory factors in synoviocytes by activating the MEK/ERK signaling pathway.