Amelogenin induces M2 macrophage polarisation via PGE2/cAMP signalling pathway

M2 Macrophages Enhance the Cementoblastic Differentiation of Periodontal Ligament Stem Cells via the Akt and JNK Pathways

“…During the pathogenesis of periodontitis, the progressive destruction of periodontal supporting tissues is initiated and caused by the local persistent inflammatory response to bacterial insult, which has been found to be associated with a high ratio of M1 Mφs to M2 Mφs and hence a decrease in local regulatory processes . Conversely, inducing a phenotypic switch of Mφs from M1 to M2 has been demonstrated to be effective in preventing alveolar bone loss and mediating periodontal tissue regrowth (for examples, see ). In recent years, it has become increasingly apparent that Mφs are central players at the onset of many tissue‐destructive diseases (for examples, see ), including periodontitis (for examples, see ); the polarization of Mφs into M1 subsets or M2 subsets in response to various surrounding environments exerts unique influences on stem cell functionality and tissue damage/repair processes .…”

“…It has become increasingly clear that different polarization states of Mφs exert different influences, most likely via paracrine action, on their cocultured cells in vitro (for example, see ) and their surrounding neighbors in vivo (for examples, see ). Although both the M1 and M2 phenotypes are involved in and necessary for many if not all wound healing cascades, a high ratio of wound healing Mφs normally leads to a favorable tissue regenerative outcome, which includes regeneration of the periodontium (for examples, see ). Therefore, modulating proper Mφ polarization to provide a delicate balance of cytokines and mediators is a critical target for tissue regeneration (for examples, see ).…”

“…Therefore, modulating proper Mφ polarization to provide a delicate balance of cytokines and mediators is a critical target for tissue regeneration (for examples, see ). Although in vitro and in vivo studies have demonstrated the crucial role of Mφs in cell osteogenesis , particularly in coaxing M2 polarization to either prevent tissue damage or enhance periodontal regenerative outcomes , how polarized Mφ phenotypes influence the cementoblastic differentiation of PDLSCs, the main cell source responsible for periodontal metabolism and turnover, remains completely unexplored.…”

Amelogenin Downregulates Interferon Gamma-Induced Major Histocompatibility Complex Class II Expression Through Suppression of Euchromatin Formation in the Class II Transactivator Promoter IV Region in Macrophages

“…As such, macrophages are involved in both the destruction and regeneration of tissues, and play an important role within the interface of inflammation and tissue regeneration. In previous studies, we reported that timedependent expression of the M2 markers CD163 and CD206 was upregulated when macrophages were stimulated with rM180 amelogenin, and that cell morphology was changed to a spindle shape, promoting differentiation into M2 macrophages (45). Additionally, inflammatory gene expression such as TNF-α, IL-6 induced by LPS was rapidly induced at 4 h post-stimulation, and returned to baseline at 24 h in the amelogenin pretreatment group, while in macrophages stimulated with LPS alone, such gene expression prolonged up to 96 h. In the amelogenin pretreatment group, the expression of anti-inflammatory genes, on the contrary, increased at 8 h post-LPS stimulation (46).…”

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“…Macrophages polarized from a pro‐inflammatory (M1) to an anti‐inflammatory/wound healing phenotype (M2) aid the creation of a microenvironment that favors wound healing and tissue growth thanks, in part, to the secretion of paracrine acting factors. Researchers led by Bei‐Min Tian and Fa‐Ming Chen (Fourth Military Medical University, Xi'an, China) knew of studies highlighting the ability of M2 macrophages to both prevent periodontal tissue damage and enhance periodontal regeneration , and in their recent Stem Cells article, they sought to understand the influence of polarized macrophages on the differentiation of hPDLSCs into cementoblasts, the cells responsible for the formation of the root cementum . Li et al revealed that M2 macrophages prompted an increase in cementoblastic differentiation‐related gene and protein expression (e.g., BSP, CAP, OCN, and CEMP1), an enhancement in cementoblast‐like cell differentiation, and the elevation of alkaline phosphatase activity (known to regulate mineralized tissue formation) in hPDLSCs.…”