Macrophage‐derived apoptotic bodies impair the osteogenic ability of osteoblasts in periodontitis

Author:

Liu Xu1,Guo Lijia2,Du Juan1,Luo Zhenhua1,Xu Junji1,Bhawal Ujjal Kumar34,Li Xiaoyan1,Liu Yi1ORCID

Affiliation:

1. Laboratory of Tissue Regeneration and Immunology and Department of Periodontics, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, School of Stomatology Capital Medical University Beijing China

2. Department of Orthodontics School of Stomatology Capital Medical University Beijing China

3. Research Institute of Oral Science, Nihon University School of Dentistry at Matsudo Matsudo Chiba Japan

4. Center for Global Health Research, Saveetha Medical College and Hospitals Saveetha Institute of Medical and Technical Sciences, Saveetha University Chennai India

Abstract

AbstractObjectivesPeriodontitis is induced by the imbalance between osteoblast and osteoclast activity, which leads to periodontal tissue destruction. Macrophages play a vital role in periodontitis. However, the hypoxic periodontal environment will also induce macrophage apoptosis within a short time. Apoptotic bodies (ABs) are the major products generated from apoptotic cells, but whether macrophage‐derived ABs play a regulatory role as their mother cells in periodontitis remains unknown. In the present study, we aimed to investigate the effects of ABs on osteoblasts.MethodABs derived from hypoxia‐induced macrophages were co‐cultured with osteoblasts and the impact of ABs on osteoblast differentiation in vitro was assessed. In vivo, periodontitis model was established and macrophages‐derived ABs were injected into the gingival sulcus. The effects of ABs on periodontal bone resorption were determined.ResultsThe results showed that ABs significantly inhibit osteoblast differentiation and promoted alveolar bone resorption in periodontitis. MicroRNA (miRNAs) array analysis was performed and revealed that miR‐483‐5p is the key miRNA in ABs. Dual luciferase reporter assays were performed and confirmed that miR‐483‐5p targeted Col1A1 mRNA and attenuated its expression.ConclusionMacrophage‐derived ABs inhibit osteoblast differentiation via the transfer of miR‐483‐5p, which downregulates Col1A1 expression and finally suppresses osteogenic activity.

Funder

Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support

National Natural Science Foundation of China

Publisher

Wiley

Subject

General Dentistry,Otorhinolaryngology

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