Hyperlipidemia promotes neutrophil extracellular trap-mediated osteonecrosis of the femoral head following methylprednisolone pulse in lupus mice

Ogawa, Hodaka; Ogawa, Naho; Fukuyama, Mizuki; Homma, Shota; Arai, Suishin; Uchizawa, Momo; Manabe, Riku; Takai, Koki; Washio, China; Hori, Ikuma; Nishibata, Yuka; Masuda, Sakiko; Sakurai, Toshihiro; Hui, Shu-Ping; Watanabe-Kusunoki, Kanako; Nakazawa, Daigo; Tomaru, Utano; Shimizu, Tomohiro; Iwasaki, Norimasa; Ishizu, Akihiro

Hyperlipidemia promotes neutrophil extracellular trap-mediated osteonecrosis of the femoral head following methylprednisolone pulse in lupus mice

Ogawa, Hodaka; Ogawa, Naho; Fukuyama, Mizuki et al.

Immunobiology, 2026, 231(3)

Permalink : https://hdl.handle.net/2115/99420

このアイテムのアクセス数:49件（2026-07-20 06:20 集計）

閲覧可能ファイル

ファイル	フォーマット	サイズ	閲覧回数	説明
https://doi.org/10.1016/j.imbio.2026.153178			29

論文情報

ファイル出力 EndNote Basic出力 Mendeley出力

アクセス権	open access
URI	https://hdl.handle.net/2115/99420
タイトル	Hyperlipidemia promotes neutrophil extracellular trap-mediated osteonecrosis of the femoral head following methylprednisolone pulse in lupus mice
著者	Ogawa, Hodaka ; Ogawa, Naho ; Fukuyama, Mizuki ; Homma, Shota ; Arai, Suishin ; Uchizawa, Momo ; Manabe, Riku ; Takai, Koki ; Washio, China ; Hori, Ikuma ; Nishibata, Yuka ; Masuda, Sakiko ; Sakurai, Toshihiro ; Hui, Shu-Ping ; Watanabe-Kusunoki, Kanako ; Nakazawa, Daigo ; Tomaru, Utano ; Shimizu, Tomohiro ; Iwasaki, Norimasa ; Ishizu, Akihiro
著者名 Ogawa, Hodaka
著者名 Ogawa, Naho
著者名 Fukuyama, Mizuki
著者名 Homma, Shota
著者名 Arai, Suishin
著者名 Uchizawa, Momo
著者名 Manabe, Riku
著者名 Takai, Koki
著者名 Washio, China
ORCID 0009-0000-3260-5440 著者名 Hori, Ikuma
e-Rad_Researcher 90899791 著者名 Nishibata, Yuka
ORCID 0009-0006-8414-7094 著者名 Masuda, Sakiko
ORCID 0000-0003-1759-3802 著者名 Sakurai, Toshihiro
ORCID 0000-0001-9973-6461 著者名 Hui, Shu-Ping
ORCID 0000-0001-8760-8630 著者名 Watanabe-Kusunoki, Kanako
著者名 Nakazawa, Daigo
ORCID 0000-0001-7929-9874 著者名 Tomaru, Utano
著者名 Shimizu, Tomohiro
ORCID 0000-0002-5496-4046 著者名 Iwasaki, Norimasa
ORCID 0000-0002-7084-9734 著者名 Ishizu, Akihiro
言語	英語
キーワード	Osteonecrosis of the femoral head
	Methylprednisolone pulse therapy
	Prenylcysteine oxidase 1
	Neutrophil extracellular traps
発行日	2026-05
出版者	Elsevier
収録物名	Immunobiology
巻(号)	231(3)
抄録	Methylprednisolone (mPSL) pulse therapy is an essential treatment for systemic lupus erythematosus (SLE); however, it carries a risk of osteonecrosis of the femoral head (ONFH). The pathogenesis of ONFH involves neutrophil extracellular trap (NET)-mediated microcirculation disorders. In BALB/c mice with imiquimod (IMQ)-induced lupus, mPSL pulse elevated serum levels of prenylcysteine oxidase 1 (PCYOX1), an enzyme that produces NET inducers hydrogen peroxide and farnesal, resulting in increased NETs in vivo. Although ischemia was observed in the femoral head, IMQ+mPSL-treated BALB/c mice did not develop ONFH. PCYOX1 is abundant in very-low-density lipoproteins. This study aimed to demonstrate that hyperlipidemia exacerbates NET-mediated microcirculation disorders and leads to ONFH development following mPSL pulse in lupus mice. To address this, ApoE mutant hyperlipidemic and BALB/c mice with IMQ-induced lupus received mPSL pulse. NET-forming neutrophils in peripheral blood were detected by flow cytometry. ONFH was assessed microscopically. As a result, IMQ+mPSL-treated ApoE mutant but not BALB/c mice developed ONFH, exhibiting higher levels of PCYOX1 and NET-forming neutrophils in circulation. In addition, NET-forming neutrophils accumulated in the vessels surrounding the femoral head, accompanied by osteocyte necrosis. This study demonstrated that mPSL pulse in lupus mice with hyperlipidemia enhanced PCYOX1 levels and NET formation, resulting in ONFH development, suggesting that hyperlipidemia may be a risk factor for ONFH following mPSL pulse therapy in SLE.
資源タイプ	学術雑誌論文
出版タイプ	Version of Record
権利情報	Creative Commons Attribution-NonCommercial 4.0
EISSN	1878-3279
関連情報	PMID 41965185
関連情報 (isIdenticalTo)	出版社版DOI https://doi.org/10.1016/j.imbio.2026.153178