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Bone Formation is Affected by Matrix Advanced Glycation End Products (AGEs) In Vivo

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Abstract

Advanced glycation end products (AGEs) accumulate in bone extracellular matrix as people age. Although previous evidence shows that the accumulation of AGEs in bone matrix may impose significant effects on bone cells, the effect of matrix AGEs on bone formation in vivo is still poorly understood. To address this issue, this study used a unique rat model with autograft implant to investigate the in vivo response of bone formation to matrix AGEs. Fluorochrome biomarkers were sequentially injected into rats to label the dynamic bone formation in the presence of elevated levels of matrix AGEs. After sacrificing animals, dynamic histomorphometry was performed to determine mineral apposition rate (MAR), mineralized surface per bone surface (MS/BS), and bone formation rate (BFR). Finally, nanoindentation tests were performed to assess mechanical properties of newly formed bone tissues. The results showed that MAR, MS/BS, and BFR were significantly reduced in the vicinity of implant cores with high concentration of matrix AGEs, suggesting that bone formation activities by osteoblasts were suppressed in the presence of elevated matrix AGEs. In addition, MAR and BFR were found to be dependent on the surrounding environment of implant cores (i.e., cortical or trabecular tissues). Moreover, MS/BS and BFR were also dependent on how far the implant cores were away from the growth plate. These observations suggest that the effect of matrix AGEs on bone formation is dependent on the biological milieu around the implants. Finally, nanoindentation test results indicated that the indentation modulus and hardness of newly formed bone tissues were not affected by the presence of elevated matrix AGEs. In summary, high concentration of matrix AGEs may slow down the bone formation process in vivo, while imposing little effects on bone mineralization.

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Acknowledgments

The authors are grateful of Dr. Bijay Giri for his assistance in handling all animal works for this study, 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, Room 414, Yifu Building, No. 37 Xueyuan Road, Haidian District, 100191, Beijing, China

    Xiao Yang & Lian-Wen Sun

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

    Mark Appleford & Xiaodu Wang

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

    Xiao Yang, Ahmed Jenan Mostafa & Xiaodu Wang

Authors
  1. Xiao Yang
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  2. Ahmed Jenan Mostafa
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  4. Lian-Wen Sun
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Correspondence to Lian-Wen Sun or Xiaodu Wang.

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Conflict of Interest

Xiao Yang, Ahmed Jenan Mostafa, Mark Appleford, Lian-Wen Sun, and Xiaodu Wang declare no competing financial interests exist.

Human and Animal Rights

All experiments were performed in accordance with University Veterinarian & Director Laboratory Animal Resources Center at University of Texas at San Antonio for animal care, and the experimental protocols were approved by the institutional animal care and use committee (IACUC).

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Yang, X., Mostafa, A.J., Appleford, M. et al. Bone Formation is Affected by Matrix Advanced Glycation End Products (AGEs) In Vivo. Calcif Tissue Int 99, 373–383 (2016). https://doi.org/10.1007/s00223-016-0153-3

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  • DOI: https://doi.org/10.1007/s00223-016-0153-3

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