CYP7B1-mediated 25-hydroxycholesterol degradation maintains quiescence-activation balance and improves therapeutic potential of mesenchymal stem cells.

Autor:	Zhang Z; Department of Orthopedics, The Eighth Affiliated Hospital, Sun Yat-sen University, 3025# Shennan Road, Shenzhen 518000, P.R. China; Department of Orthopedics, Shenzhen Second People's Hospital, the First Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong 518035, China., Su Z; Department of Orthopedics, The Eighth Affiliated Hospital, Sun Yat-sen University, 3025# Shennan Road, Shenzhen 518000, P.R. China., Li Z; Department of Orthopedics, The Eighth Affiliated Hospital, Sun Yat-sen University, 3025# Shennan Road, Shenzhen 518000, P.R. China., Li J; Department of Orthopedics, The Eighth Affiliated Hospital, Sun Yat-sen University, 3025# Shennan Road, Shenzhen 518000, P.R. China., Yu W; Department of Orthopedics, The Eighth Affiliated Hospital, Sun Yat-sen University, 3025# Shennan Road, Shenzhen 518000, P.R. China., Ye G; Department of Orthopedics, The Eighth Affiliated Hospital, Sun Yat-sen University, 3025# Shennan Road, Shenzhen 518000, P.R. China., Lin J; Department of Orthopedics, The Eighth Affiliated Hospital, Sun Yat-sen University, 3025# Shennan Road, Shenzhen 518000, P.R. China., Che Y; Department of Orthopedics, The Eighth Affiliated Hospital, Sun Yat-sen University, 3025# Shennan Road, Shenzhen 518000, P.R. China., Xu P; Department of Orthopedics, The Eighth Affiliated Hospital, Sun Yat-sen University, 3025# Shennan Road, Shenzhen 518000, P.R. China., Zeng Y; Department of Orthopedics, The Eighth Affiliated Hospital, Sun Yat-sen University, 3025# Shennan Road, Shenzhen 518000, P.R. China., Wu Y; Center for Biotherapy, The Eighth Affiliated Hospital, Sun Yat-sen University, 3025# Shennan Road, Shenzhen 518000, P.R. China. Electronic address: wuyf@mail.sysu.edu.cn., Shen H; Department of Orthopedics, The Eighth Affiliated Hospital, Sun Yat-sen University, 3025# Shennan Road, Shenzhen 518000, P.R. China. Electronic address: shenhuiy@mail.sysu.edu.cn., Xie Z; Department of Orthopedics, The Eighth Affiliated Hospital, Sun Yat-sen University, 3025# Shennan Road, Shenzhen 518000, P.R. China. Electronic address: xiezhy23@mail.sysu.edu.cn.
Jazyk:	angličtina
Zdroj:	Cell chemical biology [Cell Chem Biol] 2024 Jul 18; Vol. 31 (7), pp. 1277-1289.e7. Date of Electronic Publication: 2024 Feb 20.
DOI:	10.1016/j.chembiol.2024.01.009
Abstrakt:	Stem cells remain quiescent in vivo and become activated in response to external stimuli. However, the mechanism regulating the quiescence-activation balance of bone-marrow-derived mesenchymal stem cells (BM-MSCs) is still unclear. Herein, we demonstrated that CYP7B1 was the common critical molecule that promoted activation and impeded quiescence of BM-MSCs under inflammatory stimulation. Mechanistically, CYP7B1 degrades 25-hydroxycholesterol (25-HC) into 7α,25-dihydroxycholesterol (7α,25-OHC), which alleviates the quiescence maintenance effect of 25-HC through Notch3 signaling pathway activation. CYP7B1 expression in BM-MSCs was regulated by NF-κB p65 under inflammatory conditions. BM-MSCs from CYP7B1 conditional knockout (CKO) mice had impaired activation abilities, relating to the delayed healing of bone defects. Intravenous infusion of BM-MSCs overexpressing CYP7B1 could improve the pathological scores of mice with collagen-induced arthritis. These results clarified the quiescence-activation regulatory mechanism of BM-MSCs through the NF-κB p65-CYP7B1-Notch3 axis and provided insight into enhancing BM-MSCs biological function as well as the subsequent therapeutic effect. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2024 Elsevier Ltd. All rights reserved.)
Databáze:	MEDLINE
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