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Age-Related Effects of Advanced Glycation End Products (Ages) in Bone Matrix on Osteoclastic Resorption

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Abstract

Advanced glycation end products (AGEs) accumulate in bone extracellular matrix as people age. Previous studies have shown controversial results regarding the role of in situ AGEs accumulation in osteoclastic resorption. To address this issue, this study cultured human osteoclast cells directly on human cadaveric bone slices from different age groups (young and elderly) to warrant its relevance to in vivo conditions. The cell culture was terminated on the 3rd, 7th, and 10th day, respectively, to assess temporal changes in the number of differentiated osteoclasts, the number and size of osteoclastic resorption pits, the amount of bone resorbed, as well as the amount of matrix AGEs released in the medium by resorption. In addition, the in situ concentration of matrix AGEs at each resorption pit was also estimated based on its AGEs autofluorescent intensity. The results indicated that (1) osteoclastic resorption activities were significantly correlated with the donor age, showing larger but shallower resorption pits on the elderly bone substrates than on the younger ones; (2) osteoclast resorption activities were not significantly dependent on the in situ AGEs concentration in bone matrix, and (3) a correlation was observed between osteoclast activities and the concentration of AGEs released by the resorption. These results suggest that osteoclasts tend to migrate away from initial anchoring sites on elderly bone substrate during resorption compared to younger bone substrates. However, such behavior is not directly related to the in situ concentration of AGEs in bone matrix at the resorption sites.

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Acknowledgments

We are grateful of Mr. Evan Veregge for helping process the experimental data and the fellowship support to Ms. Xiao Yang (No. 201306020100) from China Scholarship Council (CSC).

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Authors and Affiliations

  1. School of Biological Sciences and Medical Engineering, Beihang University, Beijing, China

    Xiao Yang & Lian-Wen Sun

  2. Departments of Biomedical Engineering, The University of Texas at San Antonio (UTSA), One UTSA Circle, San Antonio, TX, 78249, USA

    Chintan Gandhi, Mark Appleford & Xiaodu Wang

  3. Department of Mechanical Engineering, The University of Texas at San Antonio (UTSA), One UTSA Circle, San Antonio, TX, 78249, USA

    Xiao Yang & Xiaodu Wang

  4. Department of Medicine, University of Texas Health Science Center at San Antonio (UTHSCSA), San Antonio, USA

    MD. Mizanur Rahman

Authors
  1. Xiao Yang
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  2. Chintan Gandhi
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  4. Mark Appleford
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  5. Lian-Wen Sun
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Correspondence to Xiaodu Wang.

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Conflict of Interest

Xiao Yang, Chintan Gandhi, Md. Mizanur Rahman, Mark Appleford, Lian-Wen Sun, and Xiaodu Wang have nothing to disclose.

Human and Animal Rights and Informed Consent

The use of human cadaveric bone samples in this study was approved by the Institutional Review Board at the University of Texas at San Antonio.

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Yang, X., Gandhi, C., Rahman, M.M. et al. Age-Related Effects of Advanced Glycation End Products (Ages) in Bone Matrix on Osteoclastic Resorption. Calcif Tissue Int 97, 592–601 (2015). https://doi.org/10.1007/s00223-015-0042-1

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  • DOI: https://doi.org/10.1007/s00223-015-0042-1

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