NOX4 and its association with myeloperoxidase and osteopontin in regulating endochondral ossification.

Autor: Ko K; BK21 Four Project, Department of Medical Sciences, Soonchunhyang University, Asan 31538, Korea., Choi S; BK21 Four Project, Department of Medical Sciences, Soonchunhyang University, Asan 31538, Korea., Jo M; BK21 Four Project, Department of Medical Sciences, Soonchunhyang University, Asan 31538, Korea., Kim C; BK21 Four Project, Department of Medical Sciences, Soonchunhyang University, Asan 31538, Korea., Boonpraman N; Department of Translational Neuroscience, College of Human Medicine, Michigan State University, Grand Rapids, MI 48824, USA., Youm J; Department of Gerontology, Graduate School of East-West Medical Science, Kyunghee University, Yongin 17104, Korea., Yi SS; BK21 Four Project, Department of Medical Sciences, Soonchunhyang University, Asan 31538, Korea.; iConnectome Co., LTD, Cheonan 31168, Korea. admiral96@sch.ac.kr.
Jazyk: angličtina
Zdroj: Journal of veterinary science [J Vet Sci] 2024 Jul; Vol. 25 (4), pp. e49. Date of Electronic Publication: 2024 May 24.
DOI: 10.4142/jvs.24076
Abstrakt: Importance: Endochondral ossification plays an important role in skeletal development. Recent studies have suggested a link between increased intracellular reactive oxygen species (ROS) and skeletal disorders. Moreover, previous studies have revealed that increasing the levels of myeloperoxidase (MPO) and osteopontin (OPN) while inhibiting NADPH oxidase 4 (NOX4) can enhance bone growth. This investigation provides further evidence by showing a direct link between NOX4 and MPO, OPN in bone function.
Objective: This study investigates NOX4, an enzyme producing hydrogen peroxide, in endochondral ossification and bone remodeling. NOX4's role in osteoblast formation and osteogenic signaling pathways is explored.
Methods: Using NOX4-deficient (NOX4 -/- ) and ovariectomized (OVX) mice, we identify NOX4's potential mediators in bone maturation.
Results: NOX4 -/- mice displayed significant differences in bone mass and structure. Compared to the normal Control and OVX groups. Hematoxylin and eosin staining showed NOX4 -/- mice had the highest trabecular bone volume, while OVX had the lowest. Proteomic analysis revealed significantly elevated MPO and OPN levels in bone marrow-derived cells in NOX4 -/- mice. Immunohistochemistry confirmed increased MPO, OPN, and collagen II (COLII) near the epiphyseal plate. Collagen and chondrogenesis analysis supported enhanced bone development in NOX4 -/- mice.
Conclusions and Relevance: Our results emphasize NOX4's significance in bone morphology, mesenchymal stem cell proteomics, immunohistochemistry, collagen levels, and chondrogenesis. NOX4 deficiency enhances bone development and endochondral ossification, potentially through increased MPO, OPN, and COLII expression. These findings suggest therapeutic implications for skeletal disorders.
Competing Interests: The authors declare no conflicts of interest.
(© 2024 The Korean Society of Veterinary Science.)
Databáze: MEDLINE