The Molecular Mechanism of LPS-induced CHI3L1 Expression / 生物化学与生物物理进展

ABSTRACT

Treatment of chronic osteomyelitis has become a difficult problem in clinical medicine due to its extended pathological process,high occurrence of complication and recurrence of disease.The major pathogenesis mechanism is Gram-negative bacteria infection,such as staphylococci.LPS is an important substance found in the cell wall of Gram-negative bacteria and administration of LPS to skeleton relevant cells in vitro could simulate the pathological characteristics of osteomyelitis patients.The results of quantitative real-time PCR and Western blot showed that CHI3L1 was up-regulated obviously in the infected bone tissues of osteomyelitis patients and LPS-stimulated osteoblasts.Analysis of the luciferase activity of NF-?B reporter gene vector revealed that LPS could activate NF-?B.Bay11-7082,an inhibitor of NF-?B activation,suppressed the elevation of CHI3L1 expression induced by LPS.Pre-incubation of osteoblasts with anti-TNF-? antibody or silencing TNF-? receptor expression by siRNA inhibited the induction effect of LPS on CHI3L1.Inhibition of NF-?B activation also prevented up-regulation of TNF-? induced by LPS.In conclusion,LPS stimulated TNF-? expression through activating NF-?B,then TNF-? induced CHI3L1 expression.It was demonstrated for the first time that CHI3L1 expression is promoted in osteomyelitis and LPS-treated osteoblasts and investigates the molecular mechanism of LPS-induced CHI3L1 expression in osteoblasts.