RRC ID 72672
Author Niu J, Wan X, Yu GY, Jiang S, Yi RN, Wu YP, Ouyang SH, Liang L, Kurihara H, Sun WY, Zhu XF, Zhang RH, Cao YF, He JB, Duan WJ, Li YF, He RR.
Title Phospholipid peroxidation-driven modification of chondrogenic transcription factor mediates alkoxyl radicals-induced impairment of embryonic bone development.
Journal Redox Biol
Abstract Maternal stress has been associated with poor birth outcomes, including preterm birth, infant mortality, and low birth weight. Bone development disorders in the embryo as a result of maternal stress are believed to be mediated through oxidative stress damage. Various species of free radicals, such as alkoxyl radicals, can be formed through endogenous redox response or exogenous stimuli in the womb and transmitted to embryos. Yet, whether these free radicals lead to abnormal fetal bone development is unclear. Here, we demonstrate prenatal bone growth retardation and ferroptosis-related signals of chondrocytes were induced by classic alkoxyl radical generators. We also show that alkoxyl radicals lead to significant accumulation of oxidized phospholipids in chondrocytes, through the iron-mediated Fenton reaction in embryos. We further demonstrate a role for the lipid peroxidation end product, 4-HNE, which forms adducts with the pivotal chondrogenesis transcription factor SOX9, leading to its degradation, therefore dampening chondrogenesis. Our data define a critical role for phospholipid peroxidation in alkoxyl radicals-evoked abnormal chondrogenesis, and pinpoint it being a precise target for treating oxidative stress-related bone development disorders.
Volume 56
Pages 102437
Published 2022-10-1
DOI 10.1016/j.redox.2022.102437
PII S2213-2317(22)00209-9
PMID 36037588
PMC PMC9440361
MeSH Alcohols Bone Development Chondrogenesis Female Free Radicals / metabolism Humans Infant, Newborn Iron Lipid Peroxidation Phospholipids* / metabolism Premature Birth* Transcription Factors / metabolism
IF 9.986
Human and Animal Cells ATDC5(RCB0565)