| Summary: | 碩士 === 國立陽明大學 === 生物醫學影像暨放射科學系 === 101 === Rheumatoid arthritis (RA) is closely correlated with excessive activation of macrophages. The release of cytokines due to macrophage activation will attract more immune cells to infiltrate, result in more severe inflammatory response. Macrophages may differentiate into osteoclasts and lead to bone erosion in the joint cavity, which is the main reason for the progression of RA. Lupeol acetate (LA), a type of triterpene, has been known with capability of anti-inflammation and anticancer. In this study, we aimed to investigate the effects of liposomal lupeol acetate (Lipo-LA) on the activation of macrophages and formation of osteoclast cells. Therapeutic efficacy of LA on RA-bearing mice and possible therapeutic mechanisms were also investigated.
Methods:
For inhibition of inflammation study, LPS-stimulated RAW 264.7 cells (mouse leukaemic monocyte macrophage cell line) were treated with Lipo-LA, LA, and using curcumin as the positive control. Both TRAP staining and real time-PCR were used for the assays of RANKL-induced osteoclasts formation. For in vivo study, eight weeks old DBA/1 mice were intradermal injected with bovine type II collagens. The collagen-induced arthritis (CIA)-bearing mice were intraperitoneal injected with 100 mg/kg LA and vehicle, respectively, from day 21 to day 43. The clinical RA score, [18F]FDG/microPET imaging, H&;E staining, and immunohistochemistry were used to evaluate the therapeutic efficacy of LA and its possible therapeutic mechanism.
Results:
Lipo-LA could inhibit the release of pro-inflammatory cytokines for cell migration from LPS-induced macrophage. Lipo-LA also inhibits RANKL-induced osteoclastogenesis related gene expressions and osteoclast formation. RA-bearing mice treated with LA were shown with significant suppression of the inflammatory mediator production in the joint tissues. Notably, LA ameliorates the severity of RA via suppression of cytokines TNF- and IL-and bone erosion related proteins, such as MCP-1, COX-2, Granzyme B, MMP-9, TGF-, IL-1, OPG and RANKL in RA-bearing mice. Non-invasive imaging with [18F]FDG/microPET also showed that the significant decrease of [18F]FDG uptake in the joints of LA-treated mice as compared with those untreated.
Conclusions:
Lipo-LA could inhibit inflammation and reduction of osteoclast formation in LPS-stimulated RAW 264.7 cells. RA-bearing mice treated with LA were shown with significant suppression of intra-articular inflammation and reduction of RA
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