Macrophages with Different Polarization Phenotypes Influence Cementoblast Mineralization through Exosomes

Abstract

Root resorption is a common dental challenge that can lead to tooth loosening or even tooth loss. Among the cells involved in root resorption, cementoblasts are responsible for laying down the cementum, while macrophages with different phenotypes have also been shown to have bidirectional effects on root resorption. However, the relationship between macrophages and cementoblasts remains largely unknown. In this study, we examined the effect of macrophages with different polarization phenotypes on the mineralization of cementoblasts. Using the transwell coculture system and a conditioned medium-based coculture system, we found that compared with M0 (unpolarized macrophages), M1-polarized macrophages attenuated cementoblast mineralization, while M2-polarized macrophages enhanced cementoblast mineralization. Furthermore, by extracting M0/M1/M2 macrophage exosomes and examining their effects on the mineralization of cementoblasts, we found that the effects of macrophages on cementoblast mineralization were, at least partially, exerted by exosomes. Moreover, in vivo studies also indicated that an increased M1/M2 ratio could suppress cementoblast mineralization and bring about root resorption. During mechanical forceinduced orthodontic tooth movement (OTM), root resorption was evident on the compression side of periodontal tissue, and a higher M1/M2 ratio and weaker cementoblast mineralization were observed on the compression side than on the tension side. We also used localized lipopolysaccharide (LPS) injection to increase the M1/M2 ratio around the roots of maxillary molars, where root resorption and decreased cementoblast mineralization were also observed. Furthermore, when we injected the exosomes from M0 and M1-and M2-polarized macrophages into mice, it was observed that the cementoblast mineralization was attenuated in the group injected with M1-polarized macrophage exosomes, while it was augmented in the group injected with M2-polarized macrophage exosomes.

Understanding exosomes: Part 3—therapeutic + diagnostic potential in dentistry

“…Only 2 in vivo studies have investigated the role of exosomes in tooth movement and tooth resorption caused by tooth movement (Table 10). In the study by Zhao et al., 47 the mouse RAW264.7 monocyte cell line was investigated, including their M0, M1 and M2 phenotypes. By isolating M0/M1/M2 macrophage exosomes and analyzing their impact on cementoblast mineralization, it was found that the effects of macrophages on cementoblast mineralization were at least partially exerted by exosomes 47 .…”

“…By isolating M0/M1/M2 macrophage exosomes and analyzing their impact on cementoblast mineralization, it was found that the effects of macrophages on cementoblast mineralization were at least partially exerted by exosomes. 47 A study by Liu et al 85 found that encapsulating simvastatin into exosomes derived from PDLSCs improved simvastatin solubility and enhanced the inhibitory effect of relapse in a rat model of orthodontic tooth movement (OTM). Notably, local injection of PDLC-Exos alone could also block relapse after OTM.…”

The Applications and Potentials of Extracellular Vesicles from Different Cell Sources in Periodontal Regeneration

“…Additionally, they used the orthodontic tooth movement strategy combined with gingival crevicular injection of LPS to construct the cementum absorption model, followed by the injection of different kinds of M-EVs. Their results indicated that M2-EVs could also significantly promote cementoblast mineralization in vivo [ 106 ]. Our unpublished study demonstrated that Ckip-1 (casein kinase 2-interacting protein 1)-silenced macrophage-derived CEVs (sh-Ckip-1-EVs) possesses the characteristic of M2-EVs in facilitating cementoblast mineralization.…”

Extracellular vesicles: A potential future strategy for dental and maxillofacial tissue repair and regeneration

“…A recently published paper showed that the effects of macrophages on cementoblast mineralization were mediated by exosomes. Compared with M0 (unpolarized macrophages), M1-polarized macrophages attenuated cementoblast mineralization, while M2-polarized macrophages enhanced cementoblast mineralization ( Zhao et al, 2022 ). However, there are few articles about EVs promoting cementum regeneration.…”