Novel Preosteoclast Populations in Obesity-Associated Periodontal Disease

Abstract

Although there is a clear relationship between the degree of obesity and periodontal disease incidence, the mechanisms that underpin the links between these conditions are not completely understood. Understanding that myeloid-derived suppressor cells (MDSCs) are expanded during obesity and operate in a context-defined manner, we addressed the potential role of MDSCs to contribute toward obesity-associated periodontal disease. Flow cytometry revealed that in the spleen of mice fed a high-fat diet (HFD), expansion in monocytic MDSCs (M-MDSCs) significantly increased when compared with mice fed a low-fat diet (LFD). In the osteoclast differentiation assay, M-MDSCs isolated from the bone marrow of HFD-fed mice showed a larger number and area of osteoclasts with a greater number of nuclei. In the M-MDSCs of HFD-fed mice, several osteoclast-related genes were significantly elevated when compared with LFD-fed mice according to a focused transcriptomic platform. In experimental periodontitis, the number and percentage of M-MDSCs were greater, with a significantly larger increase in HFD-fed mice versus LFD-fed mice. In the spleen, the percentage of M-MDSCs was significantly higher in HFD-fed periodontitis-induced (PI) mice than in LFD-PI mice. Alveolar bone volume fraction was significantly reduced in experimental periodontitis and was further decreased in HFD-PI mice as compared with LFD-PI mice. The inflammation score was significantly higher in HFD-PI mice versus LFD-PI mice, with a concomitant increase in TRAP staining for osteoclast number and area in HFD-PI mice over LFD-PI mice. These data support the concept that M-MDSC expansion during obesity to become osteoclasts during periodontitis is related to increased alveolar bone destruction, providing a more detailed mechanistic appreciation of the interconnection between obesity and periodontitis.

Candidate loci shared among periodontal disease, diabetes and bone density

“…Williams and colleagues report that cellular transcriptomic landscape of patients with periodontitis involved enhanced neutrophil and leukocyte infiltration due to the exaggerated stromal cell responsiveness (2). Meanwhile, bone changes are known among diabetic patients, perhaps with partial microvascular etiology (12), and mouse models link obesity and its metabolic dysregulation-associated inflammation to the size of preosteoclasts (myeloid-derived suppressor cells) populations (34). Both the genetic correlation of T2D/BMD and the colocalization of signals at some candidate loci are consistent with previously reported connections between these phenotypes from Mendelian randomization studies (35).…”

Mendelian randomization highlights the causal association of obesity with periodontal diseases

“…An altered oral microbiome in obese individuals, characterized by increased levels and proportions of periodontal pathogens, could also mediate the link between obesity and periodontal diseases (Maciel et al, 2016). A newly proposed mechanism is the differentiation of myeloid‐derived suppressor cells into osteoclasts in obese mice, which leads to increased alveolar bone destruction (Kwack et al, 2021).…”

Obesity influences the proteome of periodontal ligament tissues following periodontitis induction in rats

“…69,70 Although the morphological analyses did not show a statistical difference in the amount of alveolar bone between the groups, the difference detected in the proteomic analysis of the periodontal ligament suggests that the activity of osteoclasts in the P group may have decreased in the analyzed period, but was maintained in the OP group. This fact may be justified by the higher TRAP expression in animals that received HFD, as demonstrated in previous studies, [70][71][72] which could progressively influence bone metabolism in subsequent periods.…”