Cellular communication network factor 3 contributes to the pathological process of rheumatoid arthritis through promoting cell senescence and osteoclastogenesis in the joint

Tokuhiro, Taiki; Matsumae, Gen; Endo, Tsutomu; Ogawa, Yuki; Ogawa, Takuya; Liyile, Chen; Nishida, Yoshio; Alhasan, Hend; Kobayashi, Hideyuki; Ebata, Taku; Shimizu, Tomohiro; Takahashi, Daisuke; Onodera, Tomohiro; Kadoya, Ken; Terkawi, M. Alaa; Iwasaki, Norimasa

Cellular communication network factor 3 contributes to the pathological process of rheumatoid arthritis through promoting cell senescence and osteoclastogenesis in the joint

Tokuhiro, Taiki; Matsumae, Gen; Endo, Tsutomu et al.

Journal of Autoimmunity, 2024, 149, 103334

Permalink : https://hdl.handle.net/2115/97321

このアイテムのアクセス数:70件（2026-08-16 01:49 集計）

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アクセス権	open access
URI	https://hdl.handle.net/2115/97321
タイトル	Cellular communication network factor 3 contributes to the pathological process of rheumatoid arthritis through promoting cell senescence and osteoclastogenesis in the joint
著者	Tokuhiro, Taiki ; Matsumae, Gen ; Endo, Tsutomu ; Ogawa, Yuki ; Ogawa, Takuya ; Liyile, Chen ; Nishida, Yoshio ; Alhasan, Hend ; Kobayashi, Hideyuki ; Ebata, Taku ; Shimizu, Tomohiro ; Takahashi, Daisuke ; Onodera, Tomohiro ; Kadoya, Ken ; Terkawi, M. Alaa ; Iwasaki, Norimasa
著者名 Tokuhiro, Taiki
著者名 Matsumae, Gen
e-Rad_Researcher 90805293 著者名 Endo, Tsutomu
著者名 Ogawa, Yuki
著者名 Ogawa, Takuya
著者名 Liyile, Chen
著者名 Nishida, Yoshio
著者名 Alhasan, Hend
著者名 Kobayashi, Hideyuki
e-Rad_Researcher 00962953 著者名 Ebata, Taku
e-Rad_Researcher 60784246 著者名 Shimizu, Tomohiro
e-Rad_Researcher 90528845 著者名 Takahashi, Daisuke
e-Rad_Researcher 70547174 著者名 Onodera, Tomohiro
e-Rad_Researcher 30374276 著者名 Kadoya, Ken
著者名 Terkawi, M. Alaa
e-Rad_Researcher 30322803 著者名 Iwasaki, Norimasa
言語	英語
キーワード	Rheumatoid arthritis
	Senescence
	Osteoclastogenesis
	CCN3
発行日	2024-11-16
出版者	Elsevier
収録物名	Journal of Autoimmunity
巻(号)	149
ページ	103334
抄録	Rheumatoid arthritis (RA) is a chronic systemic and autoimmune disease that primarily affects joints and causes pain, stiffness and swelling. The affected joints exhibit severe inflammation in the synovium and bone erosion, leading to joint deformity. Aging is an important factor facilitating the development of RA, as it is associated with an increase in the number of senescent cells and the production of the autoantibodies and proinflammatory cytokines in tissues. Given that CCN3 is highly expressed in RA joints and that its level is associated with the severity of the disease, we explored its molecular function in joints and therapeutic potential in RA. An analysis of public scRNA-seq data from the RA synovium revealed that CCN3 is expressed by an inflammatory fibroblast subset. Interestingly, stimulation with CCN3 resulted in the activation of the senescence pathway in synoviocytes and osteoclast differentiation in monocytes in vitro. Consistent with these results, the administration of CCN3 into the knee joint and onto the calvarial bone resulted in increased numbers of senescent synoviocytes in the joint and osteoclasts in the bone, respectively. Furthermore, the therapeutic potential of targeting CCN3 was evaluated in an experimental RA model. Administration of the CCN3 antibody significantly suppressed inflammation and osteoclast numbers in the joints of the RA model mice. Our findings suggest that CCN3 contributes to pathological processes in RA and represents a promising therapeutic target for the treatment of RA.
資源タイプ	学術雑誌論文
出版タイプ	Accepted Manuscript
権利情報	Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
権利情報	©2024. This manuscript version is made available under the CC-BY-NC-ND 4.0 license https://creativecommons.org/licenses/by-nc-nd/4.0/
PISSN	0896-8411
EISSN	1095-9157
関連情報	PMID 39549484
関連情報 (isVersionOf)	出版社版DOI https://doi.org/10.1016/j.jaut.2024.103334