Interleukin-17 prevents oxidative stress from damaging osteoblast formation by inhibiting autophagic degradation of metallothionein-2.
Endocr J
; 71(6): 623-633, 2024 Jun 18.
Article
en En
| MEDLINE
| ID: mdl-38644219
ABSTRACT
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Osteoblastos
/
Osteogénesis
/
Autofagia
/
Diferenciación Celular
/
Especies Reactivas de Oxígeno
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Estrés Oxidativo
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Interleucina-17
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Peróxido de Hidrógeno
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Metalotioneína
Límite:
Animals
Idioma:
En
Revista:
Endocr J
Asunto de la revista:
ENDOCRINOLOGIA
Año:
2024
Tipo del documento:
Article
País de afiliación:
China