Myeloid‐derived suppressor cells in obesity‐associated periodontal disease: A conceptual model

Kwack, Kyu Hwan; Maglaras, Victoria; Thiyagarajan, Ramkumar; Zhang, Lixia; Kirkwood, Keith L.

doi:10.1111/prd.12384

Cited by 12 publications

(6 citation statements)

References 61 publications

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“…M1 macrophages caused alveolar bone damage by producing matrix metalloproteinases (MMPs) and prostaglandin E2 (PGE2), and M2 macrophages relieved inflammation and repaired periodontium by secreting IL‐10 and TGF‐β 47 . Additionally, MDSCs could contribute to the establishment and development of periodontitis not only through increasing the quantity and activity of osteoclasts, but also through exerting immune suppression 48,49 . It should be kept in mind that certain immunocytes are double‐edged swords in periodontitis, which can play different or even opposite roles in diverse stages of disease progression.…”

Section: Discussionmentioning

confidence: 99%

Development of a classification model and an immune‐related network based on ferroptosis in periodontitis

Tan

et al. 2023

J of Periodontal Research

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Background and Objectives Periodontitis is an immunoinflammatory disease characterized by irreversible periodontal attachment loss and bone destruction. Ferroptosis is a kind of immunogenic cell death that depends on the participation of iron ions and is involved in various inflammatory and immune processes. However, information regarding the relationship between ferroptosis and immunomodulation processes in periodontitis is extremely limited. The purpose of this study was to investigate the correlation between ferroptosis and immune responses in periodontitis. Methods Gene expression profiles of gingivae were collected from the Gene Expression Omnibus data portal. After detecting differentially expressed ferroptosis‐related genes (FRGs), we used univariate logistic regression analysis followed by logistic least absolute shrinkage and selection operator (LASSO) regression to establish a ferroptosis‐related classification model in an attempt to accurately distinguish periodontitis gingival tissues from healthy samples. The infiltration level of immunocytes in periodontitis was then assessed through single‐sample gene‐set enrichment analysis. Subsequently, we screened out immune‐related genes by weighted correlation network analysis and protein–protein interaction (PPI) analysis and constructed an immune‐related network based on FRGs and immune‐related genes. Results A total of 24 differentially expressed FRGs were detected, and an 8‐FRG combined signature constituted the classification model. The established model showed outstanding discriminating ability according to the results of receiver operating characteristic (ROC) curve analysis. In addition, the periodontitis samples had a higher degree of immunocyte infiltration. Activated B cells had the strongest positive correlation while macrophages had a strong negative correlation with certain FRGs, and we found that XBP1, ALOX5 and their interacting genes might be crucial genes in the immune‐related network. Conclusions The FRG‐based classification model had a satisfactory determination ability, which could bring new insights into the pathogenesis of periodontitis. Those genes in the immune‐related network, especially hub genes along with XBP1 and ALOX5, would have the potential to serve as promising targets of immunomodulatory treatments for periodontitis.

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Section: Discussionmentioning

confidence: 99%

Development of a classification model and an immune‐related network based on ferroptosis in periodontitis

Tan

et al. 2023

J of Periodontal Research

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“…It is notable that macrophages and osteoclasts share the same myeloid cell lineage and common monocytic cell embryology [ 121 ]. Recently, Kwack et al [ 122 ] postulated a conceptual “two-hit” model to explain obesity-exacerbated alveolar bone destruction, namely that obesity expands specific myeloid progenitor subpopulations (first hit), then is transported to the periodontal inflammatory site to differentiate into monocytes (osteoclasts) which led to obesity-associated alveolar bone loss (second hit) in a context-dependent manner ( Figure 1 , lower panel).…”

Section: Mechanisms By Which Obesity Enhances Periodontal Bone Lossmentioning

confidence: 99%

Obesity, Bone Loss, and Periodontitis: The Interlink

Zhao

Leung

2022

Biomolecules

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Obesity and periodontitis are both common health concerns that have given rise to considerable economic and societal burden worldwide. There are established negative relationships between bone metabolism and obesity, obesity and diabetes mellitus (DM), and DM and periodontitis, to name a few, with osteoporosis being considered a long-term complication of obesity. In the oral cavity, bone metabolic disorders primarily display as increased risks for periodontitis and alveolar bone loss. Obesity-driven alveolar bone loss and mandibular osteoporosis have been observed in animal models without inoculation of periodontopathogens. Clinical reports have also indicated a possible association between obesity and periodontitis. This review systematically summarizes the clinical periodontium changes, including alveolar bone loss in obese individuals. Relevant laboratory-based reports focusing on biological interlinks in obesity-associated bone remodeling via processes like hyperinflammation, immune dysregulation, and microbial dysbiosis, were reviewed. We also discuss the potential mechanism underlying obesity-enhanced alveolar bone loss from both the systemic and periodontal perspectives, focusing on delineating the practical considerations for managing periodontal disease in obese patients.

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“…In acute infections, it is proposed that MDSCs may have a beneficial role when the stimulus has been cleared by limiting tissue damage produced for a persistent immune response [ 9 ]. In contrast, during chronic inflammation, expansion and activation of MDSCs contribute to immunosuppression and oxidative stress [ 10 , 11 ]. However, differentiation and function of MDSCs are influenced by the inflammatory microenvironment generated, suggesting a disease-specific function of MDSCs.…”

Section: Introductionmentioning

confidence: 99%

“…A number of recent publications have reported that MDSCs can function as osteoclast progenitors in pathological conditions with complications associated with bone destruction [ 10 , 11 , 15 , 16 ], including collagen-induced arthritis models [ 17 ]. However, no studies have addressed MDSCs in the context of osteoarthritis.…”

Section: Introductionmentioning

confidence: 99%

“…However, no studies have addressed MDSCs in the context of osteoarthritis. Obesity has been shown to enhance MDSC expansion and obesity-related metabolic factors [ 11 , 18 ], and our group has recently shown that MDSCs are metaboloically regrogrammed during osteoclast differentiation [ 19 ]. In particular, altered levels of adipokines contribute to OA development by inducing the expression of proinflammatory factors as well as degradative enzymes, leading to the breakdown of cartilage matrix, inhibition of new cartilage matrix synthesis, and stimulation of subchondral bone remodeling [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

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Expansion of myeloid-derived suppressor cells contributes to metabolic osteoarthritis through subchondral bone remodeling

et al. 2021

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Background Osteoarthritis (OA) subsequent to acute joint injury accounts for a significant proportion of all arthropathies. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of myeloid progenitor cells classically known for potent immune-suppressive activity; however, MDSCs can also differentiate into osteoclasts. In addition, this population is known to be expanded during metabolic disease. The objective of this study was to determine the role of MDSCs in the context of OA pathophysiology. Methods In this study, we examined the differentiation and functional capacity of MDSCs to become osteoclasts in vitro and in vivo using mouse models of OA and in MDSC quantitation in humans with OA pathology relative to obesity status. Results We observed that MDSCs are expanded in mice and humans during obesity. MDSCs were expanded in peripheral blood of OA subjects relative to body mass index and in mice fed a high-fat diet (HFD) compared to mice fed a low-fat diet (LFD). In mice, monocytic MDSC (M-MDSC) was expanded in diet-induced obesity (DIO) with a further expansion after destabilization of the medial meniscus (DMM) surgery to induce post-traumatic OA (PTOA) (compared to sham-operated controls). M-MDSCs from DIO mice had a greater capacity to form osteoclasts in culture with increased subchondral bone osteoclast number. In humans, we observed an expansion of M-MDSCs in peripheral blood and synovial fluid of obese subjects compared to lean subjects with OA. Conclusion These data suggest that MDSCs are reprogrammed in metabolic disease, with the potential to contribute towards OA progression and severity.

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Myeloid‐derived suppressor cells in obesity‐associated periodontal disease: A conceptual model

Cited by 12 publications

References 61 publications

Development of a classification model and an immune‐related network based on ferroptosis in periodontitis

Development of a classification model and an immune‐related network based on ferroptosis in periodontitis

Obesity, Bone Loss, and Periodontitis: The Interlink

Expansion of myeloid-derived suppressor cells contributes to metabolic osteoarthritis through subchondral bone remodeling

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