Concanavalin A Directly Stimulates Bone-Resorbing Activity of Osteoclasts and Their Gene Expression of Cathepsin K/OC-2

1997 ◽  
Vol 234 (3) ◽  
pp. 600-604 ◽  
Author(s):  
Shinji Kakudo ◽  
Hiroshi Mano ◽  
Miho Shiokawa ◽  
Yoshihisa Mori ◽  
Masayoshi Kumegawa ◽  
...  
2001 ◽  
Vol 285 (2) ◽  
pp. 335-339 ◽  
Author(s):  
Susanne Corisdeo ◽  
Michael Gyda ◽  
Mone Zaidi ◽  
Baljit S. Moonga ◽  
Bruce R. Troen

2021 ◽  
Vol 12 ◽  
Author(s):  
Alexander A. Andreev-Andrievskiy ◽  
Roman A. Zinovkin ◽  
Mikhail A. Mashkin ◽  
Olga Yu. Frolova ◽  
Yuriy G. Kazaishvili ◽  
...  

Kagocel is a synthetic carboxymethylcellulose derivative copolymerized with gossypol. Clinical data evidence its safety and efficiency for the treatment of flu and other viral infections via enhancement of interferon production. The gut-associated lymphoid tissue seems a likely site of kagocel action. The study was aimed to investigate the molecular mechanisms of its action using murine Peyer’s patches lymphocytes as a test system and the cytokines production and gene expression patterns as the primary outcomes. The Peyer’s patches lymphocytes isolated from BALB/c mice were stimulated with concanavalin A, or, to mimic viral infection, with a combination of concanavalin A and TLR3 ligand poly I:C. After 24 h of stimulation the cells were treated with saline, 30, 100, or 300 μg/ml of kagocel, or, as positive controls, 300 μg/ml oats b-D-glucan or 300 μg/ml lentinan. After 24 and 72 h of incubation with these drugs cytokines production was analyzed with ELISA and gene expression pattern was investigated using nCounter Inflammation panel chips followed by bioinformatics analysis. Expression of genes involved in the inflammatory response, antiviral defense, lymphocytes survival and proliferation (C1qa, C2, C3, Ccl21a, Il11, Il1b, Il23a, Il5, Ltb4r2, Alox15, Pla2g4a, Ptger1, Mapkapk5, Hras, Ifna1, Tlr2, Mrc1, Mx2) was upregulated in kagocel-treated Peyer’s patches lymphocytes. A list of plausible transcription factors (CEBPs, IRF, NFκB, RXR, Stat, Tead4, and ZSCAN) and master-regulators has been identified (cIAP, CIKS, dock9, MEKK1, FXR, IKK, IRAK, TRAF, dsRNA:TLR3:TRIF). The changes in gene expression pattern and the outcomes of bioinformatics analysis suggest that pattern recognition receptors, TLRs and dectin-1, are the key mediators of kagocel immunomodulatory action, with the possible involvement of interferon autocrine loop. The genes upregulated with kagocel include diverse components of the innate immune defense system.


2020 ◽  
Vol 25 (1) ◽  
Author(s):  
Eliza S. Hartmann ◽  
Sabine Schluessel ◽  
Miriam I. Köhler ◽  
Felicitas Beck ◽  
Julia I. Redeker ◽  
...  

Abstract Introduction Periprosthetic fibroblast-like cells (PPFs) play an important role in aseptic loosening of arthroplasties. Various studies have examined PPF behavior in monolayer culture systems. However, the periprosthetic tissue is a three-dimensional (3D) mesh, which allows the cells to interact in a multidirectional way. The expression of bone remodeling markers of fibroblast-like cells in a multilayer environment changes significantly versus monolayer cultures without the addition of particles or cytokine stimulation. Gene expression of bone remodeling markers was therefore compared in fibroblast-like cells from different origins and dermal fibroblasts under transwell culture conditions versus monolayer cultures. Methods PPFs from periprosthetic tissues (n = 12), osteoarthritic (OA) synovial fibroblast-like cells (SFs) (n = 6), and dermal fibroblasts (DFs) were cultured in monolayer (density 5.5 × 103/cm2) or multilayer cultures (density 8.5 × 105/cm2) for 10 or 21 days. Cultures were examined via histology, TRAP staining, immunohistochemistry (anti-S100a4), and quantitative real-time PCR. Results Fibroblast-like cells (PPFs/SFs) and dermal fibroblasts significantly increased the expression of RANKL and significantly decreased the expression of ALP, COL1A1, and OPG in multilayer cultures. PPFs and SFs in multilayer cultures further showed a higher expression of cathepsin K, MMP-13, and TNF-α. In multilayer PPF cultures, the mRNA level of TRAP was also found to be significantly increased. Conclusion The multilayer cultures are able to induce significant expression changes in fibroblast-like cells depending on the nature of cellular origin without the addition of any further stimulus. This system might be a useful tool to get more in vivo like results regarding fibroblast-like cell cultures.


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