Periodontal ligament stem cells promote polarization of M2 macrophages

Abstract

Macrophages are widely distributed in a variety of tissues, and the different state of macrophages polarization is closely related to the occurrence, development, and prognosis of inflammation, including periodontitis, a chronic inflammatory disease leading to tooth loss worldwide. Periodontal ligament stem cells (PDLSCs) play a key role in immune regulation and periodontal tissues regeneration, contributing to cell-based therapy of periodontitis. However, the interactions between PDLSCs and macrophages are still elusive. The purpose of present study is to investigate the effect of PDLSCs conditioned medium (PDLSCs-CM) on the macrophage polarization and the possible mechanism. PDLSCs were isolated using tissue explant methods and characterized via multipotent differentiation test and examination of expression profiles of mesenchymal stem cells (MSCs) markers. The supernatant of PDLSCs was collected, centrifuged, filtered, and used as PDLSCs-CM. Then, PDLSCs-CM was cocultured with M0 macrophages or IL-4-and IL-13-induced M2 macrophages. The level of surface markers of M1/M2 macrophages and production of several proinflammatory or antiinflammatory factors were evaluated by flow cytometric analysis and enzyme-linked immunosorbent assay, respectively. The associated genes and proteins involved in the JNK pathway were investigated to explore the potential mechanism that may regulate PDLSCs-CM-mediated macrophage polarization. PDLSCs expressed MSCs markers, including STRO-1, CD146, CD90, and CD73, and were negative for CD34 and CD45, could undergo osteogenic and adipogenic differentiation when cultured in defined medium. After incubation with PDLSCs-CM, no significant increase of CD80+ and HLA-DR+ M1 macrophages was shown while evaluated CD209+ and CD206+ M2 macrophages were observed. In addition, the levels of anti-inflammatory factors such as IL-10, TGF-β, and CCL18 were increased instead of proinflammatory factors such as IL-1β, TNF-α with PDLSC-CM treatment. There was a decrease of JNK expression on M0 macrophages by qRT-PCR analysis and an increase of protein phosphorylation on M0 macrophages after incubation with PDLSCs-CM. Furthermore, as for the enhancement of IL-4-and IL-13-mediated M2 polarization by PDLSCs-CM, the mRNA level of

UCHL1 Impairs Periodontal Ligament Stem Cell Osteogenesis in Periodontitis

“…As a kind of MSCs localized in PDL, PDLSCs share many similarities with MSCs in immunomodulatory properties. PDLSCs could promote polarization of M2 macrophages (Liu et al 2022), facilitate regulatory T cells, and inhibit effector T cells (Shang et al 2021). Hence, modulating PDLSC-mediated immunoregulation might contribute to the therapeutic effects of UCHL1 inhibition on attenuating inflammation in periodontitis.…”

Immune senescence and periodontitis: From mechanism to therapy

“…For example, some studies employ immunomodulatory drugs to suppress the secretion of TNF‐α, IL‐6, and various proteases with tissue‐destroying properties by neutrophils 197,198 . In addition, the balance conversion between the 3 groups of immune cells, namely M1/M2 macrophages, Th1/Th2 cells and Th17/Treg cells, has also been an attractive research focus in the immunomodulation of periodontitis 11,199–202 …”

“…197,198 In addition, the balance conversion between the 3 groups of immune cells, namely M1/M2 macrophages, Th1/Th2 cells and Th17/Treg cells, has also been an attractive research focus in the immunomodulation of periodontitis. 11,[199][200][201][202] Bioactive reagents are the most frequently investigated in the immunotherapy of periodontitis. To date, plenty of immunomodulatory reagents have been reported in associated literatures, such as cytokines (IL-4, TGF-β, etc.…”

Protective Actions in Apical Periodontitis: The Regenerative Bioactivities Led by Mesenchymal Stem Cells

“…In vitro experiments using the conditioned medium of PDLSCs (PDLSC-CM) to treat macrophages also confirmed the in vivo findings. M0 macrophages incubated with PDLSC-CM led to increased CD209 + and CD206 + M2 macrophages [ 96 ]. A higher expression of anti-inflammatory factors, including IL-10, TGF-β, and CCL18, was observed in the PDLSC-CM-treated group, while the pro-inflammatory molecule TNF-α was downregulated [ 95 , 96 ].…”