Osteoprotective Effects of IL-33/ST2 Link to Osteoclast Apoptosis

Lima, Izabella L. A.; Macari, Soraia; Madeira, Mila Fernandes Moreira; Rodrigues, Letícia Fernanda Duffles; Colavite, Priscila María; Garlet, Gustavo; Soriani, Frederico Marianetti; Teixeira, Mauro Martins; Fukada, Sandra Yasuyo; Silva, Tarcı́lia Aparecida

doi:10.1016/j.ajpath.2015.08.013

Cited by 33 publications

(39 citation statements)

References 35 publications

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“…Moreover, there are multiple mechanisms for estrogen effects on bone cells, such as a blockade of osteoclast differentiation and activation, and an increase in the rate of apoptosis . We observed that the OTM and osteoclast numbers were increased in both ST2 −/− and OVX WT mice, confirming the osteoprotective effects of IL‐33 and estrogen on alveolar bone remodeling . However, our findings showed that under the condition of estrogen deficiency, a similar amount of tooth movement was observed in ST2 −/− OVX mice compared with that in WT OVX and ST2 −/− ‐intact mice.…”

Section: Discussionsupporting

confidence: 58%

“…2 In our study, ovariectomy and the lack of ST2 decreased the osteoblast number at the distal side of the OTM, which is in agreement with the literature. 15 However, in the presence of both estrogen and ST2 (WT-intact mice) or in their complete absence (ST2 −/− OVX mice), the osteoblast count recovered in the maxillary bone. These results suggest that there is an unclear underlying mechanism through which IL-33 plays a role in osteoblast downregulation in the alveolar bone due to a lack of estrogen.…”

Section: St2 −/− Ovx Mice Have Increased Levels Of Il-10 and Sema3amentioning

confidence: 99%

“…The number of mice per group was chosen based on a sample size estimation, 31,32 and this size has proven to yield reliable results in previous studies from our group using similar methodologies. 15,20,22,[33][34][35][36][37][38][39][40][41] Moreover, the experiment was repeated twice. On the 18th day after OVX, alveolar bone remodeling was induced by mechanical loading for 12 days.…”

Section: Animalsmentioning

confidence: 99%

“…Previous observations demonstrated that IL-33 is a potent suppressor of osteoclast activation 8,13 via induction of osteoclast apoptosis. 15 Moreover, there are multiple mechanisms for estrogen effects on bone cells, such as a blockade of osteoclast differentiation and activation, and an increase in the rate of apoptosis. 5 We observed that the OTM and osteoclast numbers were increased in both ST2 −/− and OVX WT mice, confirming the osteoprotective effects of IL-33 and estrogen on alveolar bone remodeling.…”

Section: St2 −/− Ovx Mice Have Increased Levels Of Il-10 and Sema3amentioning

confidence: 99%

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ST2 regulates bone loss in a site‐dependent and estrogen‐dependent manner

Macari

Madeira

Lima

et al. 2018

J of Cellular Biochemistry

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Interleukin-33 (IL-33) and its receptor, ST2, are implicated in bone remodeling. The lack of estrogen after menopause results in an accelerated bone loss. Here we investigated the role of ST2 in the bone loss induced by estrogen deficiency. ST2-deficient mice (ST2 ) and their littermates (wildtype [WT]) were ovariectomized (OVX), while ovary-intact mice were used as controls. Bone sites were analyzed by microcomputed tomography, histomorphometry, and quantitative real-time polymerase chain reaction (qPCR). Deletion of IL-33 or ST2 resulted in a similar bone loss in the femur and maxilla. Ovariectomy in WT mice caused bone loss in the same areas. The lack of ST2 in OVX mice did not alter bone remodeling in the femur but prevented bone loss in the maxilla. Consistently, ovariectomy increased the IL-33 messenger RNA (mRNA) levels in the maxilla but not in the femur. Under mechanical stimulation, ovariectomy and ST2 deletion independently increased bone remodeling induced by orthodontic tooth movement, which was also associated with a greater number of osteoclasts and a reduced number of osteoblasts in the maxillary bone. ST2 OVX mice, however, displayed twice as many osteoblasts as that of WT OVX mice. Ovariectomy and ST2 deletion differently altered the cytokine mRNA levels in the maxilla. Remarkably, interleukin-10 expression was decreased in both WT OVX and ST2 mice, and this reduction was completely restored in ST2 OVX mice. The results demonstrate that estrogen and IL33/ST2 independently protect against bone loss. However, the ovariectomy-induced bone loss is IL-33/ST2-dependent in the maxilla but not in the femur, indicating a bimodal and site-specific role of ST2 in bone remodeling.

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Section: Discussionsupporting

confidence: 58%

Section: St2 −/− Ovx Mice Have Increased Levels Of Il-10 and Sema3amentioning

confidence: 99%

Section: Animalsmentioning

confidence: 99%

Section: St2 −/− Ovx Mice Have Increased Levels Of Il-10 and Sema3amentioning

confidence: 99%

See 2 more Smart Citations

ST2 regulates bone loss in a site‐dependent and estrogen‐dependent manner

Macari

Madeira

Lima

et al. 2018

J of Cellular Biochemistry

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“…[62] Similarly, under OTM, ERαKO mice show an increase in the RANKL/OPG ratio, RANK, IL-6, and ST2, as well as decreased expression of dentin matrix acidic phosphoprotein and alkaline phosphatase in periodontal tissue. [63] Estrogen deficiency affects the rate of alveolar bone remodeling overall and secondarily the rate of experimental tooth movement, as shown in ovariectomized (OVX) rats undergoing lateral orthodontic tooth movement, where OVX specimens showed significantly (p<.001) increased rates of experimental tooth movement. [64, 56]…”

Section: Osteoporosis Tooth Movement and Earr In Orthodonticsmentioning

confidence: 99%

Bone Density and Dental External Apical Root Resorption

Iglesias-Linares

Morford

Hartsfield

2016

Curr Osteoporos Rep

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When orthodontic patients desire shorter treatment times with aesthetic results and long-term stability, it is important for the orthodontist to understand the potential limitations and problems that may arise during standard and/or technology-assisted accelerated treatment. Bone density plays an important role in facilitating orthodontic tooth movement (OTM), such that reductions in bone density can significantly increase movement velocity. Lifestyle, genetic background, environmental factors and disease status all can influence a patients’ overall health and bone density. In some individuals, these factors may create specific conditions that influence systemic-wide bone metabolism. Both genetic variation and the onset of a bone-related disease can influence systemic bone density and local bone density, such as is observed in the mandible and maxilla. These types of localized density changes can affect the rate of OTM and may also influence the risk of unwanted outcomes, i.e., the occurrence of dental external apical root resorption (EARR).

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Whole transcriptome analysis of smoker palatal mucosa identifies multiple downregulated innate immunity genes

Wang

Anderson

Tatakis

2020

Journal of Periodontology

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BackgroundSmoking has significant negative impact on periodontal health and treatment outcomes. The molecular effects of smoking on oral immune homeostasis have not been fully elucidated. The present study aimed to provide a comprehensive assessment of smoking‐associated gene expression changes in healthy palatal mucosa and to identify potentially implicated immunologic pathways.MethodsPalatal biopsies, in the form of connective tissue grafts, were obtained from periodontally healthy smokers and non‐smokers. Smoking status was biochemically verified (exhaled air CO and serum cotinine). Tissue samples were processed for next generation sequencing, quantitative real‐time polymerase chain reaction (qPCR), and immunohistochemistry. Gene set enrichment/pathway analysis and correlation analysis between gene expression and serum cotinine levels were also performed.ResultsAnalysis of palatal tissues from 12 non‐smokers and 10 smokers identified 830 significantly (P <0.05) differentially expressed genes (DEGs), 249 with fold change (FC) >2. Most increased in expression (≥5‐FC) were CYP1A1, CYP1B1, and USP17L9P; most decreased (≥6‐FC) were IL36A, DEFB4A, DEFB4B, SPRR2F, CCL20, KLK6, and ADH4. 203 DEGs (FC >2) were significantly correlated with serum cotinine levels. Significant enrichment pathways for cotinine‐associated genes include antimicrobial humoral response, regulation of humoral response and various metabolic processes. qPCR and immunohistochemistry confirmed gene and protein expression of selected DEGs.ConclusionsSmoking has a significant effect on the transcriptome of normal human palatal mucosa and seems to target genes important for innate immune defenses, which may prove to be one of the key mechanisms by which tobacco smoking leads to increased periodontitis susceptibility.

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Osteoprotective Effects of IL-33/ST2 Link to Osteoclast Apoptosis

Cited by 33 publications

References 35 publications

ST2 regulates bone loss in a site‐dependent and estrogen‐dependent manner

ST2 regulates bone loss in a site‐dependent and estrogen‐dependent manner

Bone Density and Dental External Apical Root Resorption

Whole transcriptome analysis of smoker palatal mucosa identifies multiple downregulated innate immunity genes

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