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

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REVIEW ARTICLE

Impact of diabetes mellitus simulations on bone cell behavior through in vitro models Yihan Li1 · Annie Shrestha2 · Hongmei Zhang1 · Lingjie Li1 · Dize Li1 · Tiwei Fu1 · Jinlin Song1 · Ping Ji1 · Yuanding Huang1 · Tao Chen1 Received: 17 November 2019 / Accepted: 23 March 2020 © The Japanese Society Bone and Mineral Research and Springer Japan KK, part of Springer Nature 2020

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 proinflammatory 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 bonerelated 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. Keywords  Osteoblasts · Osteoclasts · Macrophages · Periodontal ligament cells · Diabetes

Introduction

Yihan Li and Annie Shrestha contributed equally to this work. * Yuanding Huang [email protected] * Tao Chen [email protected] 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



Faculty of Dentistry, University of Toronto, Toronto, ON M5G 1G6, Canad