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Synovial cells play a crucial part in gouty arthritis, with different features for the inflammation within the joint. However, there is no information about how the synoviocytes can mediate the activation of inflammation. We hypothesized that the process of monosodium urate (MSU) crystal uptake alters the inflammatory response of synoviocytes through regulation of unknown mechanisms. Synoviocytes were stimulated with MSU crystals, and the phagocytosis index (PhIx) was evaluated by counting of cells with MSU ingested using polarized light microscopy. Additionally, transmission electron microscopy and flow cytometry were performed. Secretion of cytokines was measured by a panel of immunoassays. Changes in gene expression of hypoxia-inducible factor-1 ( HIF1A), von Hippel-Lindau ( VHL), and vascular endothelial growth factor ( VEGF) were evaluated by quantitative real-time PCR (qRT-PCR). Protein levels were detected by ELISA. MSU crystals induced a time-dependent increase in PhIx and the formation of numerous secretory vesicles and cavities located in the cytoplasm. Culture supernatants of MSU-treated cells had high levels of the cytokines IL-1β, IL-6, IL-8, TNF-α, and MCP-1, and the growth factors NGF and HGF. The decrease in HIF1A gene expression was 0.58-fold, and overexpression of VHL and VEGF genes was 1.98- and 4-fold, respectively, in MSU-treated synoviocytes compared to untreated cells. Additionally, VEGF levels were increased. The identification of phagocytosis of MSU crystals triggering an inflammatory cellular state in synoviocytes suggests a possible mechanism of synovial activation in the pathogenesis of crystal-induced arthritis. Impact statement Gout is distinguished by an inflammatory process that is mediated by phagocytosis of monosodium urate (MSU) crystals in synoviocytes by regulation of unknown mechanisms. Here we suggest that the synovial cells play a crucial role in gouty arthritis by activating inflammation by MSU uptake and increasing the secretion of pro-inflammatory cytokines IL-1β, IL-6, IL-8, TNF-α, MCP-1, and the growth factors NGF and HGF. We discuss some co-existing features in synoviocytes, including anomalous morphologies of the cells, and microvesicle formation, dysregulation in VEGF gene expression. We provide evidence that phagocytosis of MSU crystals triggers an inflammatory cellular state in synoviocytes in the pathogenesis of crystal-induced arthritis.

This work describes the preparation and characterization of biomimetic chitosan/multiwall carbon nanotubes/nano-hydroxyapatite (CTS/MWCNT/nHAp) scaffolds and their viability for bone tissue engineering applications. The cryogenic process ice segregation-induced self-assembly (ISISA) was used to fabricate 3D biomimetic CTS scaffolds. Proper combination of cryogenics, freeze-drying, nature and molecular ratio of solutes give rise to 3D porous interconnected scaffolds with clusters of nHAp distributed along the scaffold surface. The effect of doping in CNT (e.g. with oxygen and nitrogen atoms) on cell viability was tested. Under the same processing conditions, pore size was in the range of 20-150 μm and irrespective on the type of CNT. Studies on cell viability with scaffolds were carried out using human cells from periosteum biopsy. Prior to cell seeding, the immunophenotype of mesenchymal periosteum or periosteum-derived stem cells (MSCs-PCs) was characterized by flow cytometric analysis using fluorescence-activated and characteristic cell surface markers for MSCs-PCs. The characterized MSCs-PCs maintained their periosteal potential in cell cultures until the 2nd passage from primary cell culture. Thus, the biomimetic CTS/MWCNT/nHAp scaffolds demonstrated good biocompatibility and cell viability in all cases such that it can be considered as promising biomaterials for bone tissue engineering.