Advanced oxidation protein products induce pre‐osteoblast apoptosis through a nicotinamide adenine dinucleotide phosphate oxidase‐dependent, mitogen‐activated protein kinases‐mediated intrinsic apoptosis pathway
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Summary: Osteoblast apoptosis contributes to age‐related bone loss. Advanced oxidation protein products (AOPP s) are recognized as the markers of oxidative stress and potent inducers of apoptosis. We have demonstrated that AOPP accumulation was correlated with age‐related bone loss. However, the effect of AOPP s on the osteoblast apoptosis still remains unknown. Exposure of osteoblastic MC 3T3‐E1 cells to AOPP s caused the excessive generation of reactive oxygen species (ROS) by activating nicotinamide adenine dinucleotide phosphate (NADPH) oxidases. Increased ROS induced phosphorylation of mitogen‐activated protein kinases (MAPK s), which subsequently triggered intrinsic apoptosis pathway by inducing mitochondrial dysfunction, endoplasmic reticulum stress, and Ca 2+overload and eventually leads to apoptosis. Chronic AOPP loading in aged Sprague‐Dawley rats induced osteoblast apoptosis and activated NADPH oxidase signaling cascade, in combination with accelerated bone loss and deteriorated bone microstructure. Our study suggests that AOPP s induce osteoblast apoptosis by the NADPH oxidase‐dependent,MAPK‐mediated intrinsic apoptosis pathway.
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AGEs enhance levels of osterix, a transcription factor that promotes osteoblast differentiation and bone formation.
“Initially, AGEs enhance the levels of osterix, a transcription factor that promotes osteoblast differentiation and bone formation.”
From Advanced glycation end products (AGEs) and other adducts in aging-related diseases and alcohol-mediated tissue injury (2021) · cites this paper as [82]
Chronic AGE accumulation induces osteoblast apoptosis through activation of proapoptotic caspase-3, MAPK, and intracellular ROS generation.
“However, chronic AGE accumulation induces osteoblast apoptosis through activation of proapoptotic caspase-3, MAPK, and intracellular ROS generation80–82, indicating an intricate role for AGEs in bone physiology and remodeling.”
From Advanced glycation end products (AGEs) and other adducts in aging-related diseases and alcohol-mediated tissue injury (2021) · cites this paper as [82]
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- Authors
- Zhu, S., Zhuang, J., Wu, Q., Liu, Z., Liao, C., Luo, S., Chen, J., & Zhong, Z.
- Affiliations
- Department of Spinal Surgery Nanfang Hospital Southern Medical University Guangzhou China
- Nanfang Hospital (CN)
- Corresponding author
- Chen, Jian‐Ting
- ORCID
- Wu, Qian
- Venue
- Aging Cell
- Publisher
- Wiley
- Published
- 2018-04-16
- Volume
- 17
- Issue
- 4
- Pages
- e12764-e12764
- ISSN
- 1474-9718 (ISSN-L)
- 1474-9726
- PMC
- PMC6052394
- OpenAlex
- W2802971225
- Cited by
- 55
- References
- 43
- Citations by year
- 2026: 5 · 2025: 9 · 2024: 8 · 2023: 6 · 2022: 6 · 2021: 8 · 2020: 8 · 2019: 4 · 2018: 1
- FWCI
- 1.87
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Aging Cell (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81472135, 81000785)
- Natural Science Foundation of Guangdong Province (2014A030313340, 2016A030310404)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Keywords
- advanced oxidation protein products, osteoblast apoptosis, NADPH oxidase, mitogen-activated protein kinase, mitochondrial apoptosis, reactive oxygen species, mitochondrial dysfunction, endoplasmic reticulum stress, calcium overload, age-related bone loss, oxidative stress, bone microarchitecture, MC3T3-E1 cells
- MeSH terms
- Animals, Cells, Cultured, Male, Osteoblasts, 3T3 Cells, Rats, Sprague-Dawley, Apoptosis, NADPH Oxidases, Mitogen-Activated Protein Kinases, Mice, Rats, Advanced Oxidation Protein Products
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