M2 macrophages with inflammation tropism facilitate cementoblast mineralization

Abstract

Background: Cementum regeneration was regarded as the critical goal for periodontal regeneration, and M2 macrophage-based therapy was expected to be a promising strategy. However, little is known about the effects of M2 macrophages on cementoblast mineralization and tropism, especially under inflammation.Here we investigated for the first time the crosstalk between M2 macrophages and Porphyromonas gingivalis (Pg)-stimulated cementoblasts.Methods: M2 macrophages were induced with interleukin (IL)-4, and identified. CC-chemokine ligand 2 (CCL2) expression and secretion of inflammatory cementoblasts were detected by reverse transcription quantitative realtime polymerase chain reaction (RT-qPCR), western blotting (WB), immunohistochemistry for apical periodontitis (AP) mice, and by enzyme-linked immunosorbent assay. Crystal violet staining was used to observe macrophage migration. Conditional medium (CM) and transwell coculture methods were applied to evaluate the effects of M2 macrophages on cementum mineralization with or without Pg, and to explore the mechanism. Mineralizationrelated markers and pathway-related proteins were measured by RT-qPCR and WB. Results: M2 macrophages were identified successfully. We found an increase of CCL2 in cementoblasts and their supernatant. Also, higher CCL2 in cementoblasts was observed in the AP model. Superior recruitment of M2 macrophages to supernatant from Pg-stimulated cementoblasts or CCL2-containing medium was verified. Moreover, CM2 and Trans-M2 showed better mineralizationaccelerating and rescuing effects when compared to their controls, and application of p38 inhibitor partially blocked the promotion. Conclusions:Our study demonstrated the inflammation-targeting and mineralization-promoting effects of M2 macrophages on cementoblasts, which may provide evidence for M2 macrophage-based cementum regeneration.

Genetically engineered M2-like macrophage-derived exosomes for P. gingivalis-suppressed cementum regeneration: From mechanism to therapy

“…M2 macrophages were demonstrated to promote a variety of tissue regeneration, including periodontal bone regeneration [ 11 , 12 ]. Further, our previous work also verified the positive effect of M2 macrophages on cementoblast mineralization [ 13 ]. However, whether Ckip-1-silenced macrophages share the similarities with M2 macrophages in facilitating cementoblast mineralization remain unclear.…”

Tim4 deficiency reduces CD301b+ macrophage and aggravates periodontitis bone loss

“…Despite efficient induction of CD301b expression, IL-4 is clearly not unique to CD301b + macrophages, as it acts extensively on various cells including B cells, T cells, mast cells, macrophages, and so on. 46 Besides, the regulating effects of IL-4 on M2 macrophages have been well delineated, 47 which may consequently influence the functions of CD301b + macrophages in in vivo application. 20 The present data of increased or decreased CD301b + macrophages resulting from overexpression or knockdown of Tim4 might address the dilemma.…”

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

“…Li et al found that M2 macrophages promoted the cementoblastic differentiation of PDLSCs by secreting IL-10, VEGF and other cytokines to activate Akt signaling pathway [ 19 ]. Our recent work found that M2 macrophages possessed the chemotaxis to inflammatory microenvironment with high level of CCL2 from cementoblasts, and rescued P. gingivalis -suppressed cementoblast mineralization by activating p38 signaling pathway [ 105 ]. The effects of ICEVs on cementum formation was also poorly studied.…”