Interleukin-17 prevents oxidative stress from damaging osteoblast formation by inhibiting autophagic degradation of metallothionein-2
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 damag...
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The Japan Endocrine Society
2024-06-01
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| Series: | Endocrine Journal |
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| Online Access: | https://www.jstage.jst.go.jp/article/endocrj/71/6/71_EJ24-0050/_html/-char/en |
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| _version_ | 1832591908509057024 |
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| author | Xueyan Ling Cuixia Wang Qin Feng Tao Zhang |
| author_facet | Xueyan Ling Cuixia Wang Qin Feng Tao Zhang |
| author_sort | Xueyan Ling |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-61ba5168b3c3443981f82e07a0e1d195 |
| institution | Kabale University |
| issn | 1348-4540 |
| language | English |
| publishDate | 2024-06-01 |
| publisher | The Japan Endocrine Society |
| record_format | Article |
| series | Endocrine Journal |
| spelling | doaj-art-61ba5168b3c3443981f82e07a0e1d1952025-01-22T05:07:44ZengThe Japan Endocrine SocietyEndocrine Journal1348-45402024-06-0171662363310.1507/endocrj.EJ24-0050endocrjInterleukin-17 prevents oxidative stress from damaging osteoblast formation by inhibiting autophagic degradation of metallothionein-2Xueyan Ling0Cuixia Wang1Qin Feng2Tao Zhang3Department of Endocrinology, Zhongshan Hospital Xiamen University, Xiamen 361000, Fujian, ChinaDepartment of Paediatrics, Eighth People’s Hospital of Qingdao, Qingdao 266000, Shandong, ChinaDepartment of Imaging, Women and Children’s Hospital Qingdao University, Qingdao 266000, Shandong, ChinaDepartment of General Internal Medicine, Women and Children’s Hospital Qingdao University, Qingdao 266000, Shandong, ChinaInterleukin 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.https://www.jstage.jst.go.jp/article/endocrj/71/6/71_EJ24-0050/_html/-char/enautophagyinterleukin-17metallothionein-2osteoblastreactive oxygen species |
| spellingShingle | Xueyan Ling Cuixia Wang Qin Feng Tao Zhang Interleukin-17 prevents oxidative stress from damaging osteoblast formation by inhibiting autophagic degradation of metallothionein-2 Endocrine Journal autophagy interleukin-17 metallothionein-2 osteoblast reactive oxygen species |
| title | Interleukin-17 prevents oxidative stress from damaging osteoblast formation by inhibiting autophagic degradation of metallothionein-2 |
| title_full | Interleukin-17 prevents oxidative stress from damaging osteoblast formation by inhibiting autophagic degradation of metallothionein-2 |
| title_fullStr | Interleukin-17 prevents oxidative stress from damaging osteoblast formation by inhibiting autophagic degradation of metallothionein-2 |
| title_full_unstemmed | Interleukin-17 prevents oxidative stress from damaging osteoblast formation by inhibiting autophagic degradation of metallothionein-2 |
| title_short | Interleukin-17 prevents oxidative stress from damaging osteoblast formation by inhibiting autophagic degradation of metallothionein-2 |
| title_sort | interleukin 17 prevents oxidative stress from damaging osteoblast formation by inhibiting autophagic degradation of metallothionein 2 |
| topic | autophagy interleukin-17 metallothionein-2 osteoblast reactive oxygen species |
| url | https://www.jstage.jst.go.jp/article/endocrj/71/6/71_EJ24-0050/_html/-char/en |
| work_keys_str_mv | AT xueyanling interleukin17preventsoxidativestressfromdamagingosteoblastformationbyinhibitingautophagicdegradationofmetallothionein2 AT cuixiawang interleukin17preventsoxidativestressfromdamagingosteoblastformationbyinhibitingautophagicdegradationofmetallothionein2 AT qinfeng interleukin17preventsoxidativestressfromdamagingosteoblastformationbyinhibitingautophagicdegradationofmetallothionein2 AT taozhang interleukin17preventsoxidativestressfromdamagingosteoblastformationbyinhibitingautophagicdegradationofmetallothionein2 |