scholarly journals Structure-Dependent Effects of Bisphosphonates on Inflammatory Responses in Cultured Neonatal Mouse Calvaria

Antioxidants ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 503
Author(s):  
Keiko Suzuki ◽  
Sadaaki Takeyama ◽  
Shinobu Murakami ◽  
Masahiro Nagaoka ◽  
Mirei Chiba ◽  
...  

Bisphosphonates (BPs) are classified into two groups, according to their side chain structures, as nitrogen-containing BPs (NBPs) and non-nitrogen-containing BPs (non-NBPs). In this study, we examined the effects of NBPs and non-NBPs on inflammatory responses, by quantifying the inflammatory mediators, prostaglandin E2 (PGE2) and nitric oxide (NO), in cultured neonatal mouse calvaria. All examined NBPs (pamidronate, alendronate, incadronate, risedronate, zoledronate) stimulated lipopolysaccharide (LPS)-induced PGE2 and NO production by upregulating COX-2 and iNOS mRNA expression, whereas non-NBPs (etidronate, clodronate, tiludronate) suppressed PGE2 and NO production, by downregulating gene expression. Additionally, [4-(methylthio) phenylthio] methane bisphosphonate (MPMBP), a novel non-NBP with an antioxidant methylthio phenylthio group in its side chain, exhibited the most potent anti-inflammatory activity among non-NBPs. Furthermore, results of immunohistochemistry showed that the nuclear translocation of NF-κB/p65 and tyrosine nitration of cytoplasmic protein were stimulated by zoledronate, while MPMBP inhibited these phenomena, by acting as a superoxide anion (O2−) scavenger. These findings indicate that MPMBP can act as an efficacious agent that causes fewer adverse effects in patients with inflammatory bone diseases, including periodontitis and rheumatoid arthritis.

1990 ◽  
Vol 169 (2) ◽  
pp. 545-550 ◽  
Author(s):  
Hans Jörg Leis ◽  
Ernst Malle ◽  
Oskar Hoffmann ◽  
Klaus Klaushofer ◽  
Nadja Fratzl-Zelman ◽  
...  

2018 ◽  
Vol 46 (06) ◽  
pp. 1281-1296 ◽  
Author(s):  
Sang Yun Han ◽  
Young-Su Yi ◽  
Seong-Gu Jeong ◽  
Yo Han Hong ◽  
Kang Jun Choi ◽  
...  

Lilium bulbs have long been used as Chinese traditional medicines to alleviate the symptoms of various human inflammatory diseases. However, mechanisms of Lilium bulb-mediated anti-inflammatory activity and the bioactive components in Lilium bulbs remain unknown. In the present study, the anti-inflammatory activity of Lilium bulbs and the underlying mechanism of action were investigated in macrophages using Lilium bulb ethanol extracts (Lb-EE). In a dose-dependent manner, Lb-EE inhibited nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW264.7 cells and bone marrow-derived macrophages (BMDMs) without causing significant cytotoxicity. Lb-EE also down-regulated mRNA expression of inflammatory genes in LPS-stimulated RAW264.7 cells, which included inducuble nitric oxide synthase (iNOS), cyclooxygenase-2 (COX2), and tumor necrosis factor-[Formula: see text] (TNF-[Formula: see text]). Furthermore, Lb-EE markedly restored LPS-induced morphological changes in RAW264.7 cells to a normal morphology. HPLC analysis identified quercetin, luteolin, and kaempferol as bioactive components contained in Lb-EE. Mechanistic studies in LPS-stimulated RAW264.7 cells revealed that Lb-EE suppressed MyD88- and TRIF-induced NF-[Formula: see text]B transcriptional activation and the nuclear translocation of NF-[Formula: see text]B transcription factors. Moreover, Lb-EE inhibited IKK[Formula: see text]/[Formula: see text]-induced activation of the NF-[Formula: see text]B signaling pathway and IKK inhibition significantly reduced NO production in LPS-stimulated RAW264.7 cells. Taken together, these results suggest that Lb-EE plays an anti-inflammatory role by targeting IKK[Formula: see text]/[Formula: see text]-mediated activation of the NF-[Formula: see text]B signaling pathway during macrophage-mediated inflammatory responses.


1987 ◽  
Vol 244 (2) ◽  
pp. 409-415 ◽  
Author(s):  
P H Stern ◽  
D E Vance

Phosphatidylcholine metabolism was examined in neonatal mouse calvaria in vitro. Incorporation of choline into phosphatidylcholine was slow in this tissue. At 2 h after a pulse of [methyl-3H]choline only 30% of the tissue radioactivity was in the organic phase. Chromatography of the aqueous phase of the tissue extract revealed that more than half of the radioactivity was present as choline at this time. There was no accumulation of phosphocholine, which would have been expected if the cytidylyltransferase were the rate-limiting step in the CDP-choline pathway in the tissue. Choline kinase activity in calvarial cytosol was lower than choline kinase activity in liver cytosol of the same animals. No evidence for significant phosphatidylcholine synthesis through the methylation pathway was found in the calvarial tissue. Although rates of choline-phosphatidylcholine base exchange were higher in bone microsomes than in microsomes from liver, the rate of phosphatidylcholine production through this pathway appeared to be too slow to account for the phosphatidylcholine produced by the calvaria. Phosphatidylcholine synthesis in the calvaria was unaffected by 2 h of treatment with 10 nM-parathyroid hormone, 0.1 nM-0.1 microM-1 alpha,25-dihydroxycholecalciferol, 5 microM-prostaglandin E1 or 2.5 nM-salmon calcitonin, or by 17 h of treatment with 10 nM-parathyroid hormone or 0.1 nM-1 alpha,25-dihydroxycholecalciferol.


1997 ◽  
Vol 45 (6) ◽  
pp. 1046-1051 ◽  
Author(s):  
Tsutomu KANAZAWA ◽  
Yuki OHKAWA ◽  
TAKASHI KUDA ◽  
Yasushi MINOBE ◽  
Tadato TANI ◽  
...  

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