Antiseptic solutions modulate the paracrine-like activity of bone chips: differential impact of chlorhexidine and sodium hypochlorite
JOURNAL OF CLINICAL PERIODONTOLOGY
Authors: Sawada, Kosaku; Caballe-Serrano, Jordi; Bosshardt, Dieter D.; Schaller, Benoit; Miron, Richard J.; Buser, Daniel; Gruber, Reinhard
Abstract
AimChemical decontamination increases the availability of bone grafts; however, it remains unclear whether antiseptic processing changes the biological activity of bone. Materials and MethodsBone chips were incubated with four different antiseptic solutions including (1) povidone-iodine (0.5%), (2) chlorhexidine diguluconate (0.2%), (3) hydrogen peroxide (1%) and (4) sodium hypochlorite (0.25%). After 10min. of incubation, changes in the capacity of the bone-conditioned medium (BCM) to modulate gene expression of gingival fibroblasts was investigated. ResultsConditioned medium obtained from freshly prepared bone chips increased the expression of TGF- target genes interleukin 11 (IL11), proteoglycan4 (PRG4), NADPH oxidase 4 (NOX4), and decreased the expression of adrenomedullin (ADM), and pentraxin 3 (PTX3) in gingival fibroblasts. Incubation of bone chips with 0.2% chlorhexidine, followed by vigorously washing resulted in a BCM with even higher expression of IL11, PRG4 and NOX4. These findings were also detected with a decrease in cell viability and an activation of apoptosis signalling. Chlorhexidine alone, at low concentrations, increased IL11, PRG4 and NOX4 expression, independent of the TGF- receptor I kinase activity. In contrast, 0.25% sodium hypochlorite almost entirely abolished the activity of BCM, whereas the other two antiseptic solutions, 1% hydrogen peroxide and 0.5% povidone-iodine, had relatively no impact respectively. ConclusionThese invitro findings demonstrate that incubation of bone chips with chlorhexidine differentially affects the activity of the respective BCM compared to the other antiseptic solutions. The data further suggest that the main effects are caused by chlorhexidine remaining in the BCM after repeated washing of the bone chips.
The novel focal adhesion gene kindlin-2 promotes the invasion of gastric cancer cells mediated by tumor-associated macrophages
ONCOLOGY REPORTS
Authors: Shen, Zhanlong; Ye, Yingjiang; Kauttu, Tuuli; Seppanen, Hanna; Vainionpaa, Sanna; Wang, Shan; Mustonen, Harri; Puolakkainen, Pauli
Abstract
Kindlin-2 is a novel focal adhesion gene mediating the cell-extracellular matrix (ECM) adhesion. Tumor-associated macrophages (TAMs) play an important role in linking chronic inflammation to cancer progression. Both kindlin-2 and TAMs have been found to promote the invasion of gastric cancer cells in our previous studies. However, the correlation between kindlin-2 and TAMs remains unclear. Real-time RT-PCR was used to investigate kindlin-2 expression in the AGS, NCI and Hs-746T gastric cancer cell lines co-cultured with TAMs under normal or hypoxic conditions. IL8, IL10, IL11, IL17b, IL18, IL22 and IL24 expressions were measured by real-time RT-PCR in the gastric cancer lines with varying levels of kindlin-2 expression, as well as after downregulation of kindlin-2 mRNA expression by the siRNA method. We found that kindlin-2 was upregulated in all three gastric cancer cell lines when co-cultured with TAMs under normal conditions. Under hypoxic conditions, the induction of kindlin-2 expression induced by macrophages was significantly down-regulated in the Hs-746T cell line. IL8, IL11, IL17b, IL22 and IL24 expression was significantly higher in gastric cell lines with high kindlin-2 expression. Downregulation of kindlin-2 mRNA decreased IL10, IL11, IL17b, IL22 and IL24 expression but IL8 and IL18 expression was upregulated. Therefore, the novel focal adhesion gene kindlin-2 may play an important role in promoting the invasion of gastric cancer cells mediated by TAMs through regulating interleukin expression.