Sec-O-Glucosylhamaudol Inhibits RANKL-Induced Osteoclastogenesis by Repressing 5-LO and AKT/GSK3β Signaling
Sec-O-glucosylhamaudol (SOG), an active flavonoid compound derived from the root of Saposhnikovia divaricata (Turcz. ex Ledeb.) Schischk., exhibits analgesic, anti-inflammatory, and high 5-lipoxygenase (5-LO) inhibitory effects. However, its effect on osteoclastogenesis was unclear. We demonstrated...
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| Format: | Article |
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Frontiers Media S.A.
2022-04-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.880988/full |
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| author | Jinjin Cao Ming-Xue Zhou Xinyan Chen Menglu Sun Congmin Wei Qisheng Peng Zhou Cheng Wanchun Sun Hongbing Wang |
| author_facet | Jinjin Cao Ming-Xue Zhou Xinyan Chen Menglu Sun Congmin Wei Qisheng Peng Zhou Cheng Wanchun Sun Hongbing Wang |
| author_sort | Jinjin Cao |
| collection | DOAJ |
| description | Sec-O-glucosylhamaudol (SOG), an active flavonoid compound derived from the root of Saposhnikovia divaricata (Turcz. ex Ledeb.) Schischk., exhibits analgesic, anti-inflammatory, and high 5-lipoxygenase (5-LO) inhibitory effects. However, its effect on osteoclastogenesis was unclear. We demonstrated that SOG markedly attenuated RANKL-induced osteoclast formation, F-actin ring formation, and mineral resorption by reducing the induction of key transcription factors NFATc1, c-Fos, and their target genes such as TRAP, CTSK, and DC-STAMP during osteoclastogenesis. Western blotting showed that SOG significantly inhibited the phosphorylation of AKT and GSK3β at the middle–late stage of osteoclastogenesis without altering calcineurin catalytic subunit protein phosphatase-2β-Aα expression. Moreover, GSK3β inhibitor SB415286 partially reversed SOG-induced inhibition of osteoclastogenesis, suggesting that SOG inhibits RANKL-induced osteoclastogenesis by activating GSK3β, at least in part. 5-LO gene silencing by small interfering RNA in mouse bone marrow macrophages markedly reduced RANKL-induced osteoclastogenesis by inhibiting NFATc1. However, it did not affect the phosphorylation of AKT or GSK3β, indicating that SOG exerts its inhibitory effects on osteoclastogenesis by suppressing both the independent 5-LO pathway and AKT-mediated GSK3β inactivation. In support of this, SOG significantly improved bone destruction in a lipopolysaccharide-induced mouse model of bone loss. Taken together, these results suggest a potential therapeutic effect for SOG on osteoclast-related bone lysis disease. |
| first_indexed | 2024-12-11T05:33:31Z |
| format | Article |
| id | doaj.art-96b00d0052b2495b9858142f2a3ac6ae |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-11T05:33:31Z |
| publishDate | 2022-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-96b00d0052b2495b9858142f2a3ac6ae2022-12-22T01:19:22ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-04-011310.3389/fimmu.2022.880988880988Sec-O-Glucosylhamaudol Inhibits RANKL-Induced Osteoclastogenesis by Repressing 5-LO and AKT/GSK3β SignalingJinjin Cao0Ming-Xue Zhou1Xinyan Chen2Menglu Sun3Congmin Wei4Qisheng Peng5Zhou Cheng6Wanchun Sun7Hongbing Wang8Putuo People’s Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, ChinaDepartment of Neurology, Ruikang Hospital of Guangxi Traditional Chinese Medicine (TCM) University, Nanning, ChinaPutuo People’s Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, ChinaPutuo People’s Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, ChinaPutuo People’s Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, ChinaKey Laboratory of Zoonoses Research, Ministry of Education, Institute of Zoonosis, Jilin University, Changchun, ChinaPutuo People’s Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, ChinaKey Laboratory of Zoonoses Research, Ministry of Education, Institute of Zoonosis, Jilin University, Changchun, ChinaPutuo People’s Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, ChinaSec-O-glucosylhamaudol (SOG), an active flavonoid compound derived from the root of Saposhnikovia divaricata (Turcz. ex Ledeb.) Schischk., exhibits analgesic, anti-inflammatory, and high 5-lipoxygenase (5-LO) inhibitory effects. However, its effect on osteoclastogenesis was unclear. We demonstrated that SOG markedly attenuated RANKL-induced osteoclast formation, F-actin ring formation, and mineral resorption by reducing the induction of key transcription factors NFATc1, c-Fos, and their target genes such as TRAP, CTSK, and DC-STAMP during osteoclastogenesis. Western blotting showed that SOG significantly inhibited the phosphorylation of AKT and GSK3β at the middle–late stage of osteoclastogenesis without altering calcineurin catalytic subunit protein phosphatase-2β-Aα expression. Moreover, GSK3β inhibitor SB415286 partially reversed SOG-induced inhibition of osteoclastogenesis, suggesting that SOG inhibits RANKL-induced osteoclastogenesis by activating GSK3β, at least in part. 5-LO gene silencing by small interfering RNA in mouse bone marrow macrophages markedly reduced RANKL-induced osteoclastogenesis by inhibiting NFATc1. However, it did not affect the phosphorylation of AKT or GSK3β, indicating that SOG exerts its inhibitory effects on osteoclastogenesis by suppressing both the independent 5-LO pathway and AKT-mediated GSK3β inactivation. In support of this, SOG significantly improved bone destruction in a lipopolysaccharide-induced mouse model of bone loss. Taken together, these results suggest a potential therapeutic effect for SOG on osteoclast-related bone lysis disease.https://www.frontiersin.org/articles/10.3389/fimmu.2022.880988/fullSec-O-glucosylhamaudolosteoclastsNFATc1GSK3β5-lipoxygenaseAKT |
| spellingShingle | Jinjin Cao Ming-Xue Zhou Xinyan Chen Menglu Sun Congmin Wei Qisheng Peng Zhou Cheng Wanchun Sun Hongbing Wang Sec-O-Glucosylhamaudol Inhibits RANKL-Induced Osteoclastogenesis by Repressing 5-LO and AKT/GSK3β Signaling Frontiers in Immunology Sec-O-glucosylhamaudol osteoclasts NFATc1 GSK3β 5-lipoxygenase AKT |
| title | Sec-O-Glucosylhamaudol Inhibits RANKL-Induced Osteoclastogenesis by Repressing 5-LO and AKT/GSK3β Signaling |
| title_full | Sec-O-Glucosylhamaudol Inhibits RANKL-Induced Osteoclastogenesis by Repressing 5-LO and AKT/GSK3β Signaling |
| title_fullStr | Sec-O-Glucosylhamaudol Inhibits RANKL-Induced Osteoclastogenesis by Repressing 5-LO and AKT/GSK3β Signaling |
| title_full_unstemmed | Sec-O-Glucosylhamaudol Inhibits RANKL-Induced Osteoclastogenesis by Repressing 5-LO and AKT/GSK3β Signaling |
| title_short | Sec-O-Glucosylhamaudol Inhibits RANKL-Induced Osteoclastogenesis by Repressing 5-LO and AKT/GSK3β Signaling |
| title_sort | sec o glucosylhamaudol inhibits rankl induced osteoclastogenesis by repressing 5 lo and akt gsk3β signaling |
| topic | Sec-O-glucosylhamaudol osteoclasts NFATc1 GSK3β 5-lipoxygenase AKT |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.880988/full |
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