Redox Biology (Oct 2022)
Phospholipid peroxidation-driven modification of chondrogenic transcription factor mediates alkoxyl radicals-induced impairment of embryonic bone development
- Jie Niu,
- Xin Wan,
- Gui-Yuan Yu,
- Shan Jiang,
- Ruo-Nan Yi,
- Yan-Ping Wu,
- Shu-Hua Ouyang,
- Lei Liang,
- Hiroshi Kurihara,
- Wan-Yang Sun,
- Xiao-Feng Zhu,
- Rong-Hua Zhang,
- Yun-Feng Cao,
- Jian-Bo He,
- Wen-Jun Duan,
- Yi-Fang Li,
- Rong-Rong He
Affiliations
- Jie Niu
- Guangdong Engineering Research Center of Chinese Medicine & Disease Susceptibility, Jinan University, Guangzhou, 510632, China; International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE), Jinan University, Guangzhou, 510632, China; Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, Jinan University, Guangzhou, 510632, China; Joint Laboratory of Dalian Runsheng Kangtai and Jinan University, Jinan University, China
- Xin Wan
- Guangdong Engineering Research Center of Chinese Medicine & Disease Susceptibility, Jinan University, Guangzhou, 510632, China; International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE), Jinan University, Guangzhou, 510632, China; Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, Jinan University, Guangzhou, 510632, China; Huizhou Health Sciences Polytechnic, Huizhou, 516025, China
- Gui-Yuan Yu
- Guangdong Engineering Research Center of Chinese Medicine & Disease Susceptibility, Jinan University, Guangzhou, 510632, China; International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE), Jinan University, Guangzhou, 510632, China; Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, Jinan University, Guangzhou, 510632, China
- Shan Jiang
- Guangdong Engineering Research Center of Chinese Medicine & Disease Susceptibility, Jinan University, Guangzhou, 510632, China; International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE), Jinan University, Guangzhou, 510632, China; Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, Jinan University, Guangzhou, 510632, China; Joint Laboratory of Dalian Runsheng Kangtai and Jinan University, Jinan University, China
- Ruo-Nan Yi
- Guangdong Engineering Research Center of Chinese Medicine & Disease Susceptibility, Jinan University, Guangzhou, 510632, China; International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE), Jinan University, Guangzhou, 510632, China; Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, Jinan University, Guangzhou, 510632, China
- Yan-Ping Wu
- Guangdong Engineering Research Center of Chinese Medicine & Disease Susceptibility, Jinan University, Guangzhou, 510632, China; International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE), Jinan University, Guangzhou, 510632, China; Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, Jinan University, Guangzhou, 510632, China; Integrated Chinese and Western Medicine Department, School of Traditional Chinese Medicine, Jinan University, Guangzhou, 510632, China; Joint Laboratory of Dalian Runsheng Kangtai and Jinan University, Jinan University, China
- Shu-Hua Ouyang
- Guangdong Engineering Research Center of Chinese Medicine & Disease Susceptibility, Jinan University, Guangzhou, 510632, China; International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE), Jinan University, Guangzhou, 510632, China; Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, Jinan University, Guangzhou, 510632, China; Integrated Chinese and Western Medicine Department, School of Traditional Chinese Medicine, Jinan University, Guangzhou, 510632, China; Joint Laboratory of Dalian Runsheng Kangtai and Jinan University, Jinan University, China
- Lei Liang
- Guangdong Engineering Research Center of Chinese Medicine & Disease Susceptibility, Jinan University, Guangzhou, 510632, China; International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE), Jinan University, Guangzhou, 510632, China; Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, Jinan University, Guangzhou, 510632, China; Integrated Chinese and Western Medicine Department, School of Traditional Chinese Medicine, Jinan University, Guangzhou, 510632, China; Joint Laboratory of Dalian Runsheng Kangtai and Jinan University, Jinan University, China
- Hiroshi Kurihara
- Guangdong Engineering Research Center of Chinese Medicine & Disease Susceptibility, Jinan University, Guangzhou, 510632, China; International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE), Jinan University, Guangzhou, 510632, China; Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, Jinan University, Guangzhou, 510632, China; Joint Laboratory of Dalian Runsheng Kangtai and Jinan University, Jinan University, China
- Wan-Yang Sun
- Guangdong Engineering Research Center of Chinese Medicine & Disease Susceptibility, Jinan University, Guangzhou, 510632, China; International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE), Jinan University, Guangzhou, 510632, China; Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, Jinan University, Guangzhou, 510632, China; Joint Laboratory of Dalian Runsheng Kangtai and Jinan University, Jinan University, China
- Xiao-Feng Zhu
- Guangdong Provincial Key Laboratory of Traditional Chinese Medicine Informatization, Jinan University, Guangzhou, 510632, China
- Rong-Hua Zhang
- Guangdong Provincial Key Laboratory of Traditional Chinese Medicine Informatization, Jinan University, Guangzhou, 510632, China
- Yun-Feng Cao
- Joint Laboratory of Dalian Runsheng Kangtai and Jinan University, Jinan University, China; Shanghai Institute for Biomedical and Pharmaceutical Technologies, NHC Key Laboratory of Reproduction Regulation, ShangHai 200032, China
- Jian-Bo He
- Guangdong Engineering Research Center of Chinese Medicine & Disease Susceptibility, Jinan University, Guangzhou, 510632, China; International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE), Jinan University, Guangzhou, 510632, China; Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, Jinan University, Guangzhou, 510632, China; Integrated Chinese and Western Medicine Department, School of Traditional Chinese Medicine, Jinan University, Guangzhou, 510632, China; Joint Laboratory of Dalian Runsheng Kangtai and Jinan University, Jinan University, China; Corresponding author. Guangdong Engineering Research Center of Chinese Medicine & Disease Susceptibility, Jinan University, Guangzhou, 510632, China.
- Wen-Jun Duan
- Guangdong Engineering Research Center of Chinese Medicine & Disease Susceptibility, Jinan University, Guangzhou, 510632, China; International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE), Jinan University, Guangzhou, 510632, China; Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, Jinan University, Guangzhou, 510632, China; Integrated Chinese and Western Medicine Department, School of Traditional Chinese Medicine, Jinan University, Guangzhou, 510632, China; Joint Laboratory of Dalian Runsheng Kangtai and Jinan University, Jinan University, China; Corresponding author. Guangdong Engineering Research Center of Chinese Medicine & Disease Susceptibility, Jinan University, Guangzhou, 510632, China.
- Yi-Fang Li
- Guangdong Engineering Research Center of Chinese Medicine & Disease Susceptibility, Jinan University, Guangzhou, 510632, China; International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE), Jinan University, Guangzhou, 510632, China; Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, Jinan University, Guangzhou, 510632, China; Joint Laboratory of Dalian Runsheng Kangtai and Jinan University, Jinan University, China; Corresponding author. Guangdong Engineering Research Center of Chinese Medicine & Disease Susceptibility, Jinan University, Guangzhou, 510632, China.
- Rong-Rong He
- Guangdong Engineering Research Center of Chinese Medicine & Disease Susceptibility, Jinan University, Guangzhou, 510632, China; International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE), Jinan University, Guangzhou, 510632, China; Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, Jinan University, Guangzhou, 510632, China; Integrated Chinese and Western Medicine Department, School of Traditional Chinese Medicine, Jinan University, Guangzhou, 510632, China; Joint Laboratory of Dalian Runsheng Kangtai and Jinan University, Jinan University, China; Corresponding author. Guangdong Engineering Research Center of Chinese Medicine & Disease Susceptibility, Jinan University, Guangzhou, 510632, China.
- Journal volume & issue
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Vol. 56
p. 102437
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.
