Volume 49 Number 3

Lipopolysaccharide promotes the osteoclastogenesis through the autophagic degradationof TNF receptor-associated factor 3

Jing Hu^a, Xianyou Zeng^a, Chengcheng Song^b,*, Lei Zhang^b,*

 
ABSTRACT:     Lipopolysaccharide (LPS) is a pro-osteoclastogenic factor and autophagic activator. TNF receptorassociated factor (TRAF) 3, an anti-osteoclastogenic factor, can be degraded by autophagic activation. The effect of LPS on the level of TRAF3 during the osteoclastogenesis keeps vague. In this study, we investigated the roles of LPS in the expression patterns of TRAF3 in vivo and in vitro. Combined with the application of autophagic pharmacological inhibitors, we observed the significance of LPS-regulated autophagy in TRAF3 protein level. Moreover, we explored the effects of TRAF3 on LPS-induced osteoclastogenesis using gain-of-function and loss-of-function assays in vitro. Our study showed that LPS could reduce the protein level of TRAF3 in osteoclast precursors (OCPs) in vitro and in vivo, while no affecting the mRNA expression of TRAF3. In addition, TRAF3 overexpression reversed LPS-induced osteoclastogenesis. Importantly, LPS-inhibited TRAF3 protein level was recovered by autophagic inhibition with chloroquine or bafilomycin. Furthermore, LPS-induced osteoclastogenesis was suppressed by chloroquine, which was reversed by TRAF3 silencing. In conclusion, LPS can promote the autophagic degradation of TRAF3, which serves as an indispensable underlying mechanism in LPS-induced osteoclastogenesis

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* Corresponding author, E-mail: SCCDJY@yeah.net, 282772709@qq.com

Received 23 Oct 2021, Accepted 27 Feb 2022