Inhibition of CCL2 by bindarit alleviates diabetes-associated periodontitis by suppressing inflammatory monocyte infiltration and altering macrophage properties

Zongshan Shen; Shuhong Kuang; Min Zhang; Xin Huang; Jiayao Chen; Meiliang Guan; Wei Qin; Hockin H K Xu; Zhengmei Lin

doi:10.1038/s41423-020-0500-1

Inhibition of CCL2 by bindarit alleviates diabetes-associated periodontitis by suppressing inflammatory monocyte infiltration and altering macrophage properties

Cell Mol Immunol. 2021 Sep;18(9):2224-2235. doi: 10.1038/s41423-020-0500-1. Epub 2020 Jul 16.

Authors

Zongshan Shen^#¹, Shuhong Kuang^#¹, Min Zhang^#^{2

3}, Xin Huang¹, Jiayao Chen¹, Meiliang Guan¹, Wei Qin^{4

5

6

7}, Hockin H K Xu^{8

9

10}, Zhengmei Lin¹¹

Affiliations

¹ Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong, China.
² Department of Andrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
³ The Key Laboratory for Stem Cells and Tissue Engineering, Center for Stem Cell Biology and Tissue Engineering, Ministry of Education, Sun Yat-sen University, Guangzhou, Guangdong, China.
⁴ Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong, China. qinwei2@mail.sysu.edu.cn.
⁵ Department of Advanced Oral Sciences & Therapeutics, University of Maryland School of Dentistry, Baltimore, MD, USA. qinwei2@mail.sysu.edu.cn.
⁶ Center for Stem Cell Biology and Regenerative Medicine, University of Maryland School of Medicine, Baltimore, MD, USA. qinwei2@mail.sysu.edu.cn.
⁷ University of Maryland Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD, USA. qinwei2@mail.sysu.edu.cn.
⁸ Department of Advanced Oral Sciences & Therapeutics, University of Maryland School of Dentistry, Baltimore, MD, USA. hxu@umaryland.edu.
⁹ Center for Stem Cell Biology and Regenerative Medicine, University of Maryland School of Medicine, Baltimore, MD, USA. hxu@umaryland.edu.
¹⁰ University of Maryland Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD, USA. hxu@umaryland.edu.
¹¹ Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong, China. linzhm@mail.sysu.edu.cn.

^# Contributed equally.

Abstract

Diabetes-associated periodontitis (DP) aggravates diabetic complications and increases mortality from diabetes. DP is caused by diabetes-enhanced host immune-inflammatory responses to bacterial insult. In this study, we found that persistently elevated CCL2 levels in combination with proinflammatory monocyte infiltration of periodontal tissues were closely related to DP. Moreover, inhibition of CCL2 by oral administration of bindarit reduced alveolar bone loss and increased periodontal epithelial thickness by suppressing periodontal inflammation. Furthermore, bindarit suppressed the infiltration of proinflammatory monocytes and altered the inflammatory properties of macrophages in the diabetic periodontium. This finding provides a basis for the development of an effective therapeutic approach for treating DP.

Keywords: Diabetes-associated periodontitis; bindarit; macrophages; proinflammatory monocytes.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Chemokine CCL2 / antagonists & inhibitors*
Diabetes Mellitus*
Humans
Indazoles / pharmacology
Macrophages
Monocytes
Periodontitis* / complications
Periodontitis* / drug therapy
Propionates / pharmacology

Substances

CCL2 protein, human
Chemokine CCL2
Indazoles
Propionates
bindarit

Abstract

Publication types

MeSH terms

Substances

Grants and funding