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Article

Advanced oxidation protein products aggravate age‑related bone loss by increasing sclerostin expression in osteocytes via ROS‑dependent downregulation of Sirt1

  • Authors:
    • Jihuan Zeng
    • Qiang Xiao
    • Xiaodan Li
    • Jianting Chen
  • View Affiliations / Copyright

    Affiliations: Department of Orthopaedics and Spine Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China, Department of Orthopeadics, Jiangxi Provincial People's Hospital Affiliated to Nanchang University, Nanchang, Jiangxi 330006, P.R. China, Department of Nursing, Jiangxi Health Vocational College, Nanchang, Jiangxi 330052, P.R. China
  • Article Number: 108
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    Published online on: April 19, 2021
       https://doi.org/10.3892/ijmm.2021.4941
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Abstract

Advanced oxidation protein products (AOPPs) induce intracellular oxidative stress (OS) and are involved in numerous diseases. AOPPs accumulate with age, and our previous study revealed that AOPPs accelerated bone deterioration in aged rats. However, the underlying mechanism remains unknown. The present study demonstrated that AOPPs aggravated bone loss in aging male mice by increasing the resorptive activity and decreasing the formative activity of bone tissues. In addition, SOST mRNA (encoding sclerostin) and sclerostin protein levels were increased in the bone tissues of AOPP‑treated mice, which was associated with enhanced OS status as well as decreased Sirtuin 1 (SIRT1) mRNA and protein expression levels. Incubation of MLO‑Y4 cells with AOPPs induced the accumulation of reactive oxygen species (ROS) via the activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidases. The accumulated ROS then upregulated sclerostin expression in MLO‑Y4 cells by decreasing Sirt1 expression. In vivo, AOPP‑challenged mice co‑treated with apocynin (an inhibitor of NADPH oxidases), N‑acetyl‑L‑cysteine (a ROS scavenger) or SRT3025 (a Sirt1 activator) displayed improved bone mass and microstructure. Moreover, sclerostin expression in the bone tissues of the co‑treated groups was significantly lower compared with that in groups treated with AOPPs alone. Collectively, these data suggested that AOPPs aggravated age‑related bone loss by increasing the expression of sclerostin in osteocytes via ROS‑dependent downregulation of Sirt1. The present findings provide novel insights into the pathogenesis of senile osteoporosis.
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Copy and paste a formatted citation
Spandidos Publications style
Zeng J, Xiao Q, Li X and Chen J: Advanced oxidation protein products aggravate age‑related bone loss by increasing sclerostin expression in osteocytes via ROS‑dependent downregulation of Sirt1. Int J Mol Med 47: 108, 2021.
APA
Zeng, J., Xiao, Q., Li, X., & Chen, J. (2021). Advanced oxidation protein products aggravate age‑related bone loss by increasing sclerostin expression in osteocytes via ROS‑dependent downregulation of Sirt1. International Journal of Molecular Medicine, 47, 108. https://doi.org/10.3892/ijmm.2021.4941
MLA
Zeng, J., Xiao, Q., Li, X., Chen, J."Advanced oxidation protein products aggravate age‑related bone loss by increasing sclerostin expression in osteocytes via ROS‑dependent downregulation of Sirt1". International Journal of Molecular Medicine 47.6 (2021): 108.
Chicago
Zeng, J., Xiao, Q., Li, X., Chen, J."Advanced oxidation protein products aggravate age‑related bone loss by increasing sclerostin expression in osteocytes via ROS‑dependent downregulation of Sirt1". International Journal of Molecular Medicine 47, no. 6 (2021): 108. https://doi.org/10.3892/ijmm.2021.4941
Copy and paste a formatted citation
x
Spandidos Publications style
Zeng J, Xiao Q, Li X and Chen J: Advanced oxidation protein products aggravate age‑related bone loss by increasing sclerostin expression in osteocytes via ROS‑dependent downregulation of Sirt1. Int J Mol Med 47: 108, 2021.
APA
Zeng, J., Xiao, Q., Li, X., & Chen, J. (2021). Advanced oxidation protein products aggravate age‑related bone loss by increasing sclerostin expression in osteocytes via ROS‑dependent downregulation of Sirt1. International Journal of Molecular Medicine, 47, 108. https://doi.org/10.3892/ijmm.2021.4941
MLA
Zeng, J., Xiao, Q., Li, X., Chen, J."Advanced oxidation protein products aggravate age‑related bone loss by increasing sclerostin expression in osteocytes via ROS‑dependent downregulation of Sirt1". International Journal of Molecular Medicine 47.6 (2021): 108.
Chicago
Zeng, J., Xiao, Q., Li, X., Chen, J."Advanced oxidation protein products aggravate age‑related bone loss by increasing sclerostin expression in osteocytes via ROS‑dependent downregulation of Sirt1". International Journal of Molecular Medicine 47, no. 6 (2021): 108. https://doi.org/10.3892/ijmm.2021.4941
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