RIPK1 inhibition attenuates experimental autoimmune arthritis via suppression of osteoclastogenesis

Jooyeon Jhun; Seung Hoon Lee; Se Young Kim; Jaeyoon Ryu; Ji Ye Kwon; Hyun Sik Na; Kyoungah Jung; Su Jin Moon; Mi La Cho; Jun Ki Min

doi:10.1186/s12967-019-1809-3

RIPK1 inhibition attenuates experimental autoimmune arthritis via suppression of osteoclastogenesis

Jooyeon Jhun, Seung Hoon Lee, Se Young Kim, Jaeyoon Ryu, Ji Ye Kwon, Hyun Sik Na, Kyoungah Jung, Su Jin Moon, Mi La Cho, Jun Ki Min

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48 Scopus citations

Abstract

Background: Rheumatoid arthritis (RA) is a chronic and systemic inflammatory disease characterized by upregulation of inflammatory cell death and osteoclastogenesis. Necrostatin (NST)-1s is a chemical inhibitor of receptor-interacting serine/threonine-protein kinase (RIPK)1, which plays a role in necroptosis. Methods: We investigated whether NST-1s decreases inflammatory cell death and inflammatory responses in a mouse model of collagen-induced arthritis (CIA). Results: NST-1s decreased the progression of CIA and the synovial expression of proinflammatory cytokines. Moreover, NST-1s treatment decreased the expression of necroptosis mediators such as RIPK1, RIPK3, and mixed lineage kinase domain-like (MLKL). In addition, NST-1s decreased osteoclastogenesis in vitro and in vivo. NST-1s downregulated T helper (Th)1 and Th17 cell expression, but promoted Th2 and regulatory T (Treg) cell expression in CIA mice. Conclusions: These results suggest that NST-1s attenuates CIA progression via the inhibition of osteoclastogenesis and might be a potential therapeutic agent for RA therapy.

Original language	English
Article number	84
Journal	Journal of Translational Medicine
Volume	17
Issue number	1
DOIs	https://doi.org/10.1186/s12967-019-1809-3
State	Published - 15 Mar 2019

Bibliographical note

Funding Information:
This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Educa‑ tion (NRF 2015R1D1A1A01057072). This work was supported by the National Research Foundation of Korea (NRF) Grant funded by the Korea government (MSIT) (No. NRF‑2018R1C1B6005854).

Publisher Copyright:
© 2019 The Author(s).

Keywords

Necroptosis
Necrostatin-1s
Osteoclastogenesis
Rheumatoid arthritis

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10.1186/s12967-019-1809-3

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title = "RIPK1 inhibition attenuates experimental autoimmune arthritis via suppression of osteoclastogenesis",

abstract = "Background: Rheumatoid arthritis (RA) is a chronic and systemic inflammatory disease characterized by upregulation of inflammatory cell death and osteoclastogenesis. Necrostatin (NST)-1s is a chemical inhibitor of receptor-interacting serine/threonine-protein kinase (RIPK)1, which plays a role in necroptosis. Methods: We investigated whether NST-1s decreases inflammatory cell death and inflammatory responses in a mouse model of collagen-induced arthritis (CIA). Results: NST-1s decreased the progression of CIA and the synovial expression of proinflammatory cytokines. Moreover, NST-1s treatment decreased the expression of necroptosis mediators such as RIPK1, RIPK3, and mixed lineage kinase domain-like (MLKL). In addition, NST-1s decreased osteoclastogenesis in vitro and in vivo. NST-1s downregulated T helper (Th)1 and Th17 cell expression, but promoted Th2 and regulatory T (Treg) cell expression in CIA mice. Conclusions: These results suggest that NST-1s attenuates CIA progression via the inhibition of osteoclastogenesis and might be a potential therapeutic agent for RA therapy.",

keywords = "Necroptosis, Necrostatin-1s, Osteoclastogenesis, Rheumatoid arthritis",

author = "Jooyeon Jhun and Lee, {Seung Hoon} and Kim, {Se Young} and Jaeyoon Ryu and Kwon, {Ji Ye} and Na, {Hyun Sik} and Kyoungah Jung and Moon, {Su Jin} and Cho, {Mi La} and Min, {Jun Ki}",

note = "Funding Information: This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Educa‑ tion (NRF 2015R1D1A1A01057072). This work was supported by the National Research Foundation of Korea (NRF) Grant funded by the Korea government (MSIT) (No. NRF‑2018R1C1B6005854). Publisher Copyright: {\textcopyright} 2019 The Author(s).",

year = "2019",

month = mar,

day = "15",

doi = "10.1186/s12967-019-1809-3",

language = "English",

volume = "17",

journal = "Journal of Translational Medicine",

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T1 - RIPK1 inhibition attenuates experimental autoimmune arthritis via suppression of osteoclastogenesis

AU - Jhun, Jooyeon

AU - Lee, Seung Hoon

AU - Kim, Se Young

AU - Ryu, Jaeyoon

AU - Kwon, Ji Ye

AU - Na, Hyun Sik

AU - Jung, Kyoungah

AU - Moon, Su Jin

AU - Cho, Mi La

AU - Min, Jun Ki

N1 - Funding Information: This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Educa‑ tion (NRF 2015R1D1A1A01057072). This work was supported by the National Research Foundation of Korea (NRF) Grant funded by the Korea government (MSIT) (No. NRF‑2018R1C1B6005854). Publisher Copyright: © 2019 The Author(s).

PY - 2019/3/15

Y1 - 2019/3/15

N2 - Background: Rheumatoid arthritis (RA) is a chronic and systemic inflammatory disease characterized by upregulation of inflammatory cell death and osteoclastogenesis. Necrostatin (NST)-1s is a chemical inhibitor of receptor-interacting serine/threonine-protein kinase (RIPK)1, which plays a role in necroptosis. Methods: We investigated whether NST-1s decreases inflammatory cell death and inflammatory responses in a mouse model of collagen-induced arthritis (CIA). Results: NST-1s decreased the progression of CIA and the synovial expression of proinflammatory cytokines. Moreover, NST-1s treatment decreased the expression of necroptosis mediators such as RIPK1, RIPK3, and mixed lineage kinase domain-like (MLKL). In addition, NST-1s decreased osteoclastogenesis in vitro and in vivo. NST-1s downregulated T helper (Th)1 and Th17 cell expression, but promoted Th2 and regulatory T (Treg) cell expression in CIA mice. Conclusions: These results suggest that NST-1s attenuates CIA progression via the inhibition of osteoclastogenesis and might be a potential therapeutic agent for RA therapy.

AB - Background: Rheumatoid arthritis (RA) is a chronic and systemic inflammatory disease characterized by upregulation of inflammatory cell death and osteoclastogenesis. Necrostatin (NST)-1s is a chemical inhibitor of receptor-interacting serine/threonine-protein kinase (RIPK)1, which plays a role in necroptosis. Methods: We investigated whether NST-1s decreases inflammatory cell death and inflammatory responses in a mouse model of collagen-induced arthritis (CIA). Results: NST-1s decreased the progression of CIA and the synovial expression of proinflammatory cytokines. Moreover, NST-1s treatment decreased the expression of necroptosis mediators such as RIPK1, RIPK3, and mixed lineage kinase domain-like (MLKL). In addition, NST-1s decreased osteoclastogenesis in vitro and in vivo. NST-1s downregulated T helper (Th)1 and Th17 cell expression, but promoted Th2 and regulatory T (Treg) cell expression in CIA mice. Conclusions: These results suggest that NST-1s attenuates CIA progression via the inhibition of osteoclastogenesis and might be a potential therapeutic agent for RA therapy.

KW - Necroptosis

KW - Necrostatin-1s

KW - Osteoclastogenesis

KW - Rheumatoid arthritis

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DO - 10.1186/s12967-019-1809-3

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AN - SCOPUS:85062953451

SN - 1479-5876

VL - 17

JO - Journal of Translational Medicine

JF - Journal of Translational Medicine

IS - 1

M1 - 84

ER -

RIPK1 inhibition attenuates experimental autoimmune arthritis via suppression of osteoclastogenesis

Abstract

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