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The concept that inflammation serves a leading role in osteoclast-induced bone loss under pathological circumstances is now widely accepted. In the present study, it was observed that lipopolysaccharides (LPSs) demonstrated a synergic effect on receptor activator of nuclear factor κ-B ligand (RANKL)-induced osteoclast differentiation in Raw264.7 cells, with increasing levels of multiple pro-inflammatory cytokines including interleukin (IL)-6, tumor necrosis factor-α and IL-1β. Furthermore, microRNA (miR)-146a was highly induced by LPS and RANKL co-stimulation during the process of osteoclast differentiation. Overexpression of miR-146a inhibited osteoclast transformation by targeting the key regulators of nuclear factor (NF)-κβ signaling, TNF receptor-associated factor 6 and interleukin-1 receptor-associated kinase 1. The downstream activation of NF-κβ signaling was also inhibited by transfection with a miR-146a mimic. Altogether, the results of the present study demonstrated that miR-146a prevents osteoclast differentiation induced by LPS and RANKL co-stimulation, suggesting that miR-146a may be a promising therapeutic target for treatment of inflammation mediated bone loss. [ABSTRACT FROM AUTHOR]

As a cytokine of the interleukin-6 family, cardiotrophin-1 (CT-1) has been shown to be an important endogenous protector in liver injury. Our study aimed to investigate the role of CT-1 in liver fibrosis in pediatric cholestatic liver disease (PCLD). CT-1 mRNA and protein expression levels were upregulated in PCLD liver biopsy tissues compared with controls. Immunohistochemistry and confocal microscopy of liver sections showed that CT-1 was predominantly expressed by biliary epithelium cells. Serum CT-1 was elevated significantly in the children with PCLD compared with controls. Serum CT-1 levels exhibited a moderate positive correlation with the Scheuer stage of hepatic fibrosis and serum TB levels and a weak correlation with serum ALP levels. In vitro analysis indicated that LX-2 cells preconditioned with CT-1 exhibited significant increments in proliferation and accumulation of extracellular matrix components, while also positively regulating the STAT3 and p38MAPK pathways. In conclusion, biliary epithelium-derived CT-1 may exert a profibrogenic potential in PCLD. [ABSTRACT FROM AUTHOR]