Polarized Macrophages in Periodontitis: Characteristics, Function, and Molecular Signaling

Sun, Xiaoyu; Gao, Jike; Meng, Xiang; Lu, Xiaoxuan; Zhang, Lei; Chen, Ran

doi:10.3389/fimmu.2021.763334

Cited by 116 publications

(93 citation statements)

References 189 publications

(241 reference statements)

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“…Our previous study has shown that Pg LPS promotes pro-inflammatory cytokine expression, which in turn activates ERK and p38 pathways, thereby promoting macrophage polarization and osteoclast differentiation ( Chang et al, 2021 ). In line with this, pro-inflammatory cytokines such as TNF-α and IL-6 can further accelerate osteoclast maturation ( O'Brien et al, 2016 ; Chang et al, 2021 ; Sun et al, 2021 ).…”

Section: Introductionmentioning

confidence: 67%

Xanthine Derivative KMUP-1 Attenuates Experimental Periodontitis by Reducing Osteoclast Differentiation and Inflammation

et al. 2022

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Periodontitis is an inflammatory disease of gum that may predispose to serious systemic complications such as diabetes and cardiovascular diseases. Activation of macrophages and osteoclasts around periodontal tissue can accelerate gum inflammation. In addition, alteration of cyclic nucleotide levels is associated with the severity of periodontitis. Our previous study has shown that KMUP-1, a xanthine derivative exhibiting phosphodiesterase inhibition and soluble guanylyl cyclase activation, can inhibit lipopolysaccharide (LPS)-induced inflammation and receptor activator of nuclear factor kappa-Β ligand (RANKL)-induced osteoclastogenesis. This study was aimed to investigate whether KMUP-1 could attenuate periodontitis both in vitro and in vivo. In vitro, the protective effect of KMUP-1 on inflammation and osteoclastogenesis was investigated in RANKL-primed RAW264.7 cells treated by Porphyromonas gingivalis LPS (PgLPS). The results showed that KMUP-1 attenuated PgLPS-induced osteoclast differentiation as demonstrated by decreased TRAP-positive multinuclear cells and TRAP activity. This reduction of osteoclast differentiation by KMUP-1 was reversed by KT5823, a protein kinase G inhibitor. Similarly, pro-inflammatory cytokine levels induced by PgLPS were inhibited by KMUP-1 in a dose-dependent manner whereas reversed by KT5823. Mechanistically, suppression of MAPKs, PI3K/Akt, and NF-κB signaling pathways and decrease of c-Fos and NFATc1 expression in osteoclast precursors by KMUP-1 may mediate its protective effect. In vivo, two models of periodontitis in rats were induced by gingival injections of PgLPS and ligature placement around molar teeth, respectively. Our results showed that KMUP-1 inhibited alveolar bone loss in both rat models, and this effect mediated at least partly by reduced osteoclastogenesis. In conclusion, our study demonstrated the therapeutic potential of KMUP-1 on periodontitis through suppression of inflammation and osteoclast differentiation.

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Section: Introductionmentioning

confidence: 67%

Xanthine Derivative KMUP-1 Attenuates Experimental Periodontitis by Reducing Osteoclast Differentiation and Inflammation

et al. 2022

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“…Macrophages are important parts of the immune system. In periodontitis, macrophages mediate the development and progression of periodontitis through M1 and M2 polarization (97). M1 macrophages produce a series of pro-inflammatory factors including TNF-a and IL-6 to kill bacteria, promote inflammation, and activate osteoclasts that cause absorption of the alveolar ridge.…”

Section: Immune Regulation and Anti-inflammationmentioning

confidence: 99%

“…M1 macrophages produce a series of pro-inflammatory factors including TNF-a and IL-6 to kill bacteria, promote inflammation, and activate osteoclasts that cause absorption of the alveolar ridge. In contrast, M2 macrophages produce anti-inflammatory factors including IL-10 and transforming growth factor (TGF)-b to exert anti-inflammation and angiogenic effects, and activate osteoblasts to restore bone tissue (97)(98)(99). A recent study indicated that PELNs can be absorbed by intestinal macrophages and regulate immune response (86).…”

Section: Immune Regulation and Anti-inflammationmentioning

confidence: 99%

The Emerging Role of Plant-Derived Exosomes-Like Nanoparticles in Immune Regulation and Periodontitis Treatment

et al. 2022

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Periodontitis is an infectious oral disease, which leads to the destruction of periodontal tissues and tooth loss. Although the treatment of periodontitis has improved recently, the effective treatment of periodontitis and the periodontitis-affected periodontal tissues is still a challenge. Therefore, it is urgent to explore new therapeutic strategies for periodontitis. Natural products show anti-microbial, anti-inflammatory, anti-oxidant and bone protective effects to periodontitis and most of these natural products are safe and cost-effective. Among these, the plant-derived exosome-like nanoparticles (PELNs), a type of natural nanocarriers repleted with lipids, proteins, RNAs, and other active molecules, show the ability to enter mammalian cells and regulate cellular activities. Reports from the literature indicate the great potential of PELNs in the regulation of immune functions, inflammation, microbiome, and tissue regeneration. Moreover, PELNs can also be used as drug carriers to enhance drug stability and cellular uptake in vivo. Since regulation of immune function, inflammation, microbiome, and tissue regeneration are the key phenomena usually targeted during periodontitis treatment, the PELNs hold the promising potential for periodontitis treatment. This review summarizes the recent advances in PELNs-related research that are related to the treatment of periodontitis and regeneration of periodontitis-destructed tissues and the underlying mechanisms. We also discuss the existing challenges and prospects of the application of PELNs-based therapeutic approaches for periodontitis treatment.

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“…P. gingivalis is a putative keystone pathogen with the ability to impair innate immunity and transform a normally symbiotic microbiota into a dysbiotic state in periodontal tissue ( 7 ). Macrophages participate in the initiation of inflammation and are the major immune cells producing pro-inflammatory cytokines and mediating alveolar bone resorption in periodontitis ( 30 ). P. gingivalis induces M1macrophages by downregulating α-KG production ( 19 ), and M1 macrophages were the dominant phenotype for the gingival infiltration in response to P. gingivalis infection ( 31 ).…”

Section: Macrophage Polarization In P Gingivalis -...mentioning

confidence: 99%

Macrophages: A communication network linking Porphyromonas gingivalis infection and associated systemic diseases

Lin

Huang

et al. 2022

Front. Immunol.

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Porphyromonas gingivalis (P. gingivalis) is a Gram-negative anaerobic pathogen that is involved in the pathogenesis of periodontitis and systemic diseases. P. gingivalis has recently been detected in rheumatoid arthritis (RA), cardiovascular disease, and tumors, as well as Alzheimer’s disease (AD), and the presence of P. gingivalis in these diseases are correlated with poor prognosis. Macrophages are major innate immune cells which modulate immune responses against pathogens, however, multiple bacteria have evolved abilities to evade or even subvert the macrophages’ immune response, in which subsequently promote the diseases’ initiation and progression. P. gingivalis as a keystone pathogen of periodontitis has received increasing attention for the onset and development of systemic diseases. P. gingivalis induces macrophage polarization and inflammasome activation. It also causes immune response evasion which plays important roles in promoting inflammatory diseases, autoimmune diseases, and tumor development. In this review, we summarize recent discoveries on the interaction of P. gingivalis and macrophages in relevant disease development and progression, such as periodontitis, atherosclerosis, RA, AD, and cancers, aiming to provide an in-depth mechanistic understanding of this interaction and potential therapeutic strategies.

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Polarized Macrophages in Periodontitis: Characteristics, Function, and Molecular Signaling

Cited by 116 publications

References 189 publications

Xanthine Derivative KMUP-1 Attenuates Experimental Periodontitis by Reducing Osteoclast Differentiation and Inflammation

Xanthine Derivative KMUP-1 Attenuates Experimental Periodontitis by Reducing Osteoclast Differentiation and Inflammation

The Emerging Role of Plant-Derived Exosomes-Like Nanoparticles in Immune Regulation and Periodontitis Treatment

Macrophages: A communication network linking Porphyromonas gingivalis infection and associated systemic diseases

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