Inhibitory effects of LY267108 on nuclear factor kappa B during osteoclast activation

doi:10.3969/j.issn.2095-4344.2014.15.003

Abstract

Abstract:

BACKGROUND: No ideal drugs can be used in the prevention and treatment of aseptic loosening of artificial joints. Some researchs showed that erythromycin has strong inhibitory effects on periprosthetic osteolysis. Its antibacterial activity, however, limits its application in artificial joint loosening prevention. LY267108 is a new type of erythromycin derivatives, eliminates the antibacterial activities, and retains the anti-inflammatory activity.
OBJECTIVE: To evaluate inhibitory effect of LY267108 on nuclear factor kappa B during osteoclast activation.
METHODS: RANKL and macrophage colony-stimulating factor were added to RAW264.7 cell line of a mouse model induced by osteoclasts. Simultaneously, different concentrations of alendronate sodium, erythromycin and LY267108 were cocultured for 48 hours. The activity of nuclear factor kappa B and content of intracytoplasmic inhibitory subunit of nuclear factor kappa B alpha were measured by electrophoretic mobility shift assay and western blot assay.
RESULTS AND CONCLUSION: LY267108 has a strong inhibitory effect on nuclear factor kappa B. 10 mg/L LY267108, 25 mg/L erythromycin and 10 mg/L alendronate sodium had similar inhibitory effects on nuclear factor kappa B, which was obviously stronger than 10 mg/L erythromycin. However, 25 mg/L LY267108 had strongest inhibitory effects. No significant difference in intracytoplasmic inhibitory subunit of nuclear factor kappa B alpha levels was detected among 10 mg/L LY267108, 25 mg/L erythromycin and 10 mg/L alendronate sodium groups, but was still apparently higher than 10 mg/L erythromycin group. Levels of intracytoplasmic inhibitory subunit of nuclear factor kappa B alpha were highest in the 25 mg/L LY267108 group. Results indicated that LY267108 in the process of osteoclast activation had stronger inhibitory effects on nuclear factor kappa B compared with erythromycin, and its safety was higher than alendronate sodium. Simultaneously, LY267108 did not have antimicrobial activity, and became a potential ideal drug for prevention and treatment of aseptic loosening of artificial joints. However, the inhibitory effects of LY267108 on the degradation of inhibitory subunit of nuclear factor kappa B alpha would be a mechanism of inhibiting the activation of nuclear factor kappa B.

中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程

全文链接：

Key words: NF-kappa B, joint prosthesis, osteoclasts, erythromycin

CLC Number:

R318

Yu Jian, Zhao Jian-ning. Inhibitory effects of LY267108 on nuclear factor kappa B during osteoclast activation [J]. Chinese Journal of Tissue Engineering Research, 2014, 18(15): 2309-2313.

Figures/Tables 2

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