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Impact of diabetes mellitus simulations on bone cell behavior through in vitro models

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Abstract

Diabetes mellitus (DM) is related to impaired bone healing and an increased risk of bone fractures. While it is recognized that osteogenic differentiation and the function of osteoblasts are suppressed in DM, the influence of DM on osteoclasts is still unclear. Hyperglycemia and inflammatory environment are the hallmark of DM that causes dysregulation of various pro-inflammatory cytokines and alternated gene expression in periodontal ligament cells, osteoblasts, osteocytes, osteoclasts, and osteoclast precursors. A methodological review on conceptual and practical implications of in vitro study models is used for DM simulation on bone cells. Several major databases were screened to find literature related to the study objective. Published literature within last 20 years that used in vitro DM-simulated models to study how DM affects the cellular behavior of bone cells were selected for this review. Studies utilizing high glucose and serum acquired from diabetic animals are the mainly used methods to simulate the diabetic condition. The combination with various simulating factors such as lipopolysaccharide (LPS), hydrogen peroxide (H2O2), and advanced glycation end products (AGEs) have been reported in diabetic situations in vitro, as well. Through screening procedure, it was evident DM-simulated conditions exerted negative impact on bone-related cells. However, inconsistent results were found among different reported studies, which could be due to variation in culture conditions, concentrations of the stimulating factors and cell lineage, etc. This manuscript has concisely reviewed currently existing DM-simulated in vitro models and provides valuable insights of detailed components in simulating DM conditions in vitro. Studies using DM-simulated microenvironment revealed that in vitro simulation negatively impacted periodontal ligament cells, osteoblasts, osteocytes, osteoclasts, and osteoclast precursors. Contrarily, studies also indicated beneficial influence on bone-related cells when such conditions are reversed.

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Funding

This work was supported by the National Nature Science Foundation of China [Grant numbers: 81701031, 31100690], Postdoctoral Science Foundation of China [Grant number: 2017M622981], Project funded by Chongqing Special Postdoctoral Science Foundation [Grant number: XmT2018009], and Chongqing Research Program of Basic Research and Frontier Technology [Grant number: cstc2017jcyjAX0376].

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  1. Yihan Li and Annie Shrestha contributed equally to this work.

Authors and Affiliations

  1. Stomatological Hospital of Chongqing Medical University, Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, 426#Songshibei Road, Yubei District, Chongqing, 401147, P.R. China

    Yihan Li, Hongmei Zhang, Lingjie Li, Dize Li, Tiwei Fu, Jinlin Song, Ping Ji, Yuanding Huang & Tao Chen

  2. Faculty of Dentistry, University of Toronto, Toronto, ON, M5G 1G6, Canada

    Annie Shrestha

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  1. Yihan Li
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  2. Annie Shrestha
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  3. Hongmei Zhang
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  4. Lingjie Li
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Contributions

YL and AS contributed equally to this work on writing the manuscript. HZ and LL searched literatures; DL and TF analyzed and selected literature; JS and PJ gave the idea of this manuscript; YH and TC made correction of this manuscript.

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Correspondence to Yuanding Huang or Tao Chen.

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Li, Y., Shrestha, A., Zhang, H. et al. Impact of diabetes mellitus simulations on bone cell behavior through in vitro models. J Bone Miner Metab 38, 607–619 (2020). https://doi.org/10.1007/s00774-020-01101-5

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