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Osteoarthritis (OA) is a common chronic degenerative disease which is characterized by the disruption of articular cartilage. Syringic acid (SA) is a phenolic compound with anti‐inflammatory, antioxidant, and other effects including promoting osteogenesis. However, the effect of SA on OA has not yet been reported. Therefore, the purpose of our study was to investigate the effect and mechanism of SA on OA in a mouse model of medial meniscal destabilization. The expressions of genes were evaluated by qPCR or western blot or immunofluorescence. RNA‐seq analysis was performed to examine gene transcription alterations in chondrocytes treated with SA. The effect of SA on OA was evaluated using destabilization of the medial meniscus model of mice. We found that SA had no obvious toxic effect on chondrocytes, while promoting the expressions of chondrogenesis‐related marker genes. The results of RNA‐seq analysis showed that extracellular matrix–receptor interaction and transforming growth factor‐β (TGF‐β) signaling pathways were enriched among the up‐regulated genes by SA. Mechanistically, we demonstrated that SA transcriptionally activated Smad3. In addition, we found that SA inhibited the overproduction of lipopolysaccharide‐induced inflammation‐related cytokines including tumor necrosis factor‐α and interleukin‐1β, as well as matrix metalloproteinase 3 and matrix metalloproteinase 13. The cell apoptosis and nuclear factor‐kappa B (NF‐κB) signaling were also inhibited by SA treatment. Most importantly, SA attenuated cartilage degradation in a mouse OA model. Taken together, our study demonstrated that SA could alleviate cartilage degradation in OA by activating the TGF‐β/Smad and inhibiting NF‐κB signaling pathway. [ABSTRACT FROM AUTHOR]

Enhancer of zeste homolog 2 (EZH2) is an important member of the epigenetic regulatory factor polycomb group proteins (PcG) and is abnormally expressed in a wide variety of tumors, including osteosarcoma. Scientists consider EZH2 as an attractive target for the treatment of osteosarcoma and have found many potential EZH inhibitors, such as GlaxoSmithKline 343 (GSK343). It has been reported that GSK343 can be used as an inhibitor in different types of cancer. This study demonstrated that GSK343 not only induced apoptosis by increasing cleaved Casp-3 and poly ADP-ribose polymerase (PARP) expression, but also induced autophagic cell death by inhibiting p62 expression. Apoptosis and autophagic cell death induced by GSK343 were confirmed by the high expression of cleaved caspase-3, LC3-II and transmission electron microscopy. GSK343 inhibited the expression of EZH2 and c-Myc. Additionally, GSK343 inhibited the expression of FUSE binding protein 1 (FBP1), which was identified by its regulatory effects on c-Myc expression. Since c-Myc is a common target of EZH2 and FBP1, and GSK343 inhibited the expression of these proliferation-promoting proteins, a mutual regulatory mechanism between EZH2 and FBP1 was proposed. The knockdown of EZH2 suppressed the expression of FBP1; similarly, the knockdown of FBP1 suppressed the expression of EZH2. These results suggest the mutual regulatory association between EZH2 and FBP1. The knockdown of either EZH2 or FBP1 accelerated the sensitivity of osteosarcoma cells to GSK343. Based on these results, this study clarified that GSK343, an EZH2 inhibitor, may have potential for use in the treatment of osteosarcoma. The underlying mechanisms of the effects of GSK343 are partly mediated by its inhibitory activity against c-Myc and its regulators (EZH2 and FBP1). [ABSTRACT FROM AUTHOR]

Background: Bone-tendon junction (BTJ) is a unique structure connecting tendon and bone through a fibrocartilage zone. Owing to its unique structure, the regeneration of BTJ remains a challenge. Here, we study the fibrochondrogenic differentiation of human tendon-derived stem/progenitor cells (TSPCs) both in vitro and in vivo ., Methods: TSPCs were isolated from human patellar tendon tissues and investigated for their multidifferentiation potential. TSPCs were cultured in chondrogenic medium with transforming growth factor beta 3 (TGF-β3) and BMP-2 in vitro  ​and examined for the expression of fibrochondrogenic marker genes by quantitative real-time reverse transcription polymerase chain reaction, enzyme-linked immunosorbent assay, and immunofluorescence. TSPCs pretreated were also seeded in collage II sponge and then transplanted in immunocompromised nude mice to examine if the fibrochondrogenic characteristics were conserved in vivo ., Results: We found that TSPCs were differentiated towards fibrochondrogenic lineage, accompanied by the expression of collagen I, collagen II, SRY-box transcription factor 9 (Sox 9), and tenascin C. Furthermore, after TSPCs were seeded in collagen II sponge and transplanted in immunocompromised nude mice, they expressed fibrochondrogenic genes, including proteoglycan, collagen I, and collagen II., Conclusion: Taken together, this study showed that TSPCs are capable of differentiating towards fibrocartilage-like cells, and the fibrochondrogenic characteristics were conserved even in vivo , and thus might have the potential application for fibrocartilage regeneration in BTJ repair., The Translational Potential of This Article: TSPCs are able to differentiate into fibrocartilage-like cells and thus might well be one potential cell source for fibrocartilage regeneration in a damaged BTJ repair., (© 2019 Published by Elsevier (Singapore) Pte Ltd on behalf of Chinese Speaking Orthopaedic Society.)

Objective: To summarize the mechanism research progress of tendon-derived stem cells (TDSCs) in the reconstruction of fibrocartilage zone at bone-tendon junction (BTJ)., Methods: The domestic and abroad related literature about TDSCs in the reconstruction of fibrocartilage zone at BTJ was summarized and analyzed., Results: TDSCs can be induced to osteocytes, fibrochondrocytes, and tenocytes in vitro . Therefore, TDSCs have potential to reconstruct fibrocartilage zone at BTJ. Factors, such as mechanical stimulation, bioactive factor, extracelluar matrix, inflammatory factors, and so on, may influence osteogenic or chondrogenic differentiation of TDSCs., Conclusion: Because of the specificity of origin and location of TDSCs, TDSCs have the potential to be the seed cells for BTJ fibrocartilage zone repair. By applying external stimuli, TDSCs can be induced to form structures which are similar to fibrocartilage zone.

The preparation of collagen sponges was studied in order to develop tissue engineering scaffolds. Collagen solutions with varying concentrations were obtained by condensing the initial collagen with polyethylene glycol (PEG) at 4 degrees C for different periods of time, and then were freeze-dried to make collagen scaffolds. The porous characteristics of the prepared scaffolds were characterized by use of different methods, including laser scanning confocal microscopy (LSCM), scanning electron microscopy (SEM) and tensile tests. All collagen sponges were shown to have similar interconnected porous structures but were found to have different pore size, porosity, water capacity and the mechanical property, depending on the concentration of collagen solutions. These findings indicate that the way of controlling the concentration of collagen solutions with PEG permits the freeze-drying fabrication of collagen sponges with varying porous features suitable for different tissue engineering purposes.