Interleukin-17 prevents oxidative stress from damaging osteoblast formation by inhibiting autophagic degradation of metallothionein-2
ENDOCRINE JOURNAL(2024)
摘要
Interleukin 17A (IL-17A) is a key cytokine promoting osteoblast formation, which contributes to osteogenesis. IL-17A functions in autophagy inhibition within osteoblasts. Metallothionein-2 (MT-2), as an important reactive oxygen species (ROS)-scavenging molecule, prevents oxidative stress from damaging osteoblast formation. The relationship between IL-17A-regulated autophagy and MT-2 production under oxidative stress deserves further exploration. In this study, we first investigated the roles of IL-17A in osteoblastic differentiation and ROS production in osteoblast precursors in the presence of hydrogen peroxide (H2O2). Next, we explored the effects of IL-17A on autophagic activity and MT-2 protein expression in osteoblast precursors in the presence of H2O2. Ultimately, by using autophagic pharmacological agonist (rapamycin) and lentiviral transduction technology, the relationship between autophagy, IL-17A-regulated MT-2 protein expression and IL-17A-regulated ROS production was further elucidated. Our results showed that in the presence of H2O2, IL-17A promoted osteoblastic differentiation and inhibited ROS production. Moreover, in the presence of H2O2, IL-17A inhibited autophagic activity and promoted MT-2 protein expression in osteoblast precursors. Importantly, IL-17A-promoted MT-2 protein levels and -inhibited ROS production were reversed by autophagy activation with rapamycin. Furthermore, IL-17A-inhibited ROS production were blocked by MT-2 silencing. In conclusion, IL-17A promotes ROS clearance by inhibiting autophagic degradation of MT-2, thereby protecting osteoblast formation from oxidative stress.
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关键词
Autophagy,Interleukin-17,Metallothionein-2,Osteoblast,Reactive oxygen species
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