Pyroptosis in bone loss

Ji, Ling; Men, Xinrui; Chen, Xinyi; Zhi, Maohui; He, Shushu; Chen, Song

doi:10.1007/s10495-022-01807-z

Cited by 6 publications

(3 citation statements)

References 170 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The recruitment of macrophages is directly linked to the intensity of periodontal diseases [ 44 ]. Infiltrated macrophages experience a range of regulatory cell deaths, leading to the release of inflammatory substances that exacerbate periodontal disease [ 23 , 45 ]. Through the release of IL-1β, macrophage pyroptosis hastens the aging of periodontal tissue [ 22 ].…”

Section: Discussionmentioning

confidence: 99%

Copper Chelation Therapy Attenuates Periodontitis Inflammation through the Cuproptosis/Autophagy/Lysosome Axis

Zhang,

Tsai,

et al. 2024

IJMS

View full text Add to dashboard Cite

Periodontitis development arises from the intricate interplay between bacterial biofilms and the host’s immune response, where macrophages serve pivotal roles in defense and tissue homeostasis. Here, we uncover the mitigative effect of copper chelator Tetrathiomolybdate (TTM) on periodontitis through inhibiting cuproptosis, a newly identified form of cell death which is dependent on copper. Our study reveals concurrent cuproptosis and a macrophage marker within murine models. In response to lipopolysaccharide (LPS) stimulation, macrophages exhibit elevated cuproptosis-associated markers, which are mitigated by the administration of TTM. TTM treatment enhances autophagosome expression and mitophagy-related gene expression, countering the LPS-induced inhibition of autophagy flux. TTM also attenuates the LPS-induced fusion of autophagosomes and lysosomes, the degradation of lysosomal acidic environments, lysosomal membrane permeability increase, and cathepsin B secretion. In mice with periodontitis, TTM reduces cuproptosis, enhances autophagy flux, and decreases Ctsb levels. Our findings underscore the crucial role of copper-chelating agent TTM in regulating the cuproptosis/mitophagy/lysosome pathway during periodontitis inflammation, suggesting TTM as a promising approach to alleviate macrophage dysfunction. Modulating cuproptosis through TTM treatment holds potential for periodontitis intervention.

show abstract

Section: Discussionmentioning

confidence: 99%

Copper Chelation Therapy Attenuates Periodontitis Inflammation through the Cuproptosis/Autophagy/Lysosome Axis

Zhang,

Tsai,

et al. 2024

IJMS

View full text Add to dashboard Cite

show abstract

“…For example, the prolonged release of IL‐1β, IL‐6 and TNF‐α coordinates to induce severely imbalanced bone remodelling with increased bone resorption and decreased bone formation (Azuma et al., 2014; Yokota et al., 2021). To date, the Nlrp3‐mediated pyroptosis with its underlying mechanism has been thoroughly studied in the context of inflammatory bone injury (Li et al., 2023; Murakami et al., 2022; Tao et al., 2020). Negative regulation of Nlrp3 inflammasome activation has been a therapeutic strategy for inflammation‐associated diseases (Cheng et al., 2020; Coll et al., 2022).…”

Section: Discussionmentioning

confidence: 99%

Nlrp3 inflammasome drives regulatory T cell depletion to accelerate periapical bone erosion

Wang,

Liu,

Yue

et al. 2024

Int Endodontic J

View full text Add to dashboard Cite

AimApical periodontitis is an inflammatory disorder triggered by an immune response to bacterial infection, leading to the periapical tissue damage and alveolar resorption. However, the underlying mechanisms driving this process remain elusive, due to the complex and interconnected immune microenvironment within the local lesion site. In this study, the influence of Nlrp3 inflammasome‐mediated immune response on the apical periodontitis was investigated.MethodologyRNA sequencing, immunohistochemistry and ELISA assay were performed to investigate the activation of Nlrp3 inflammasome signalling pathways in the human periapical tissues, including radicular cysts, periapical granulomas and healthy oral mucosa. A mouse model of apical periodontitis was established to study the role of Nlrp3 knockout in periapical bone resorption and Treg cell stability, and the underlying mechanism was explored through in vitro experiments. In vivo Treg cell adoptive transfer was performed to investigate the effects of Treg cells on the progression of apical periodontitis.ResultsOur findings find that the hyperactivated Nlrp3 inflammasome is present in human periapical lesions and plays a vital role in the immune‐related periapical bone loss. Using a mouse model of apical periodontitis, we observe that Nlrp3 deficiency is resistant to bone resorption. This protection was accompanied by elevated generation and infiltration of local Treg cells that displayed a notable ability to suppress RANKL‐dependent osteoclast differentiation. In terms of the mechanism of action, Nlrp3 deficiency directly inhibits the osteoclast differentiation and bone loss through JNK/MAPK and NF‐κB pathways. In addition, Nlrp3 induces pyroptosis in the stem cells from apical papilla (SCAPs), and the subsequent release of cytokines affects the stability of Treg cell in periapical lesions, leading indirectly to enhanced bone resorption. In turn, adoptive transfer of both Nlrp3‐deficient and wild‐type Treg cells effectively prevent the bone erosion during apical periodontitis.ConclusionsTogether, our data identify that the Nlrp3 inflammasome modulates the Treg cell stability and osteoclastogenesis in the periapical inflammatory microenvironment, thus determining the progression of bone erosion.

show abstract

“…The NLRP3 inflammasome mediates the activation of caspase-1 (CASP1), IL-1β, and IL-18 to induce inflammation. However, overactivation of the inflammasome can also cause osteoblast dysfunction and induce pyroptosis ( 5 , 16 ).…”

Section: Introductionmentioning

confidence: 99%

Influence of metallic particles and TNF on the transcriptional regulation of NLRP3 inflammasome-associated genes in human osteoblasts

Sellin,

Hansmann,

Bader

et al. 2024

Front. Immunol.

View full text Add to dashboard Cite

IntroductionThe release of mature interleukin (IL-) 1β from osteoblasts in response to danger signals is tightly regulated by the nucleotide-binding oligomerization domain leucine-rich repeat and pyrin-containing protein 3 (NLRP3) inflammasome. These danger signals include wear products resulting from aseptic loosening of joint arthroplasty. However, inflammasome activation requires two different signals: a nuclear factor-kappa B (NF-κB)-activating priming signal and an actual inflammasome-activating signal. Since human osteoblasts react to wear particles via Toll-like receptors (TLR), particles may represent an inflammasome activator that can induce both signals.MethodsTemporal gene expression profiles of TLRs and associated intracellular signaling pathways were determined to investigate the period when human osteoblasts take up metallic wear particles after initial contact and initiate a molecular response. For this purpose, human osteoblasts were treated with metallic particles derived from cobalt-chromium alloy (CoCr), lipopolysaccharides (LPS), and tumor necrosis factor-alpha (TNF) alone or in combination for incubation times ranging from one hour to three days. Shortly after adding the particles, their uptake was observed by the change in cell morphology and spectral data.ResultsExposure of osteoblasts to particles alone increased NLRP3 inflammasome-associated genes. The response was not significantly enhanced when cells were treated with CoCr + LPS or CoCr + TNF, whereas inflammation markers were induced. Despite an increase in genes related to the NLRP3 inflammasome, the release of IL-1β was unaffected after contact with CoCr particles.DiscussionAlthough CoCr particles affect the expression of NLRP3 inflammasome-associated genes, a single stimulus was not sufficient to prime and activate the inflammasome. TNF was able to prime the NLRP3 inflammasome of human osteoblasts.

show abstract

Pyroptosis in bone loss

Cited by 6 publications

References 170 publications

Copper Chelation Therapy Attenuates Periodontitis Inflammation through the Cuproptosis/Autophagy/Lysosome Axis

Copper Chelation Therapy Attenuates Periodontitis Inflammation through the Cuproptosis/Autophagy/Lysosome Axis

Nlrp3 inflammasome drives regulatory T cell depletion to accelerate periapical bone erosion

Influence of metallic particles and TNF on the transcriptional regulation of NLRP3 inflammasome-associated genes in human osteoblasts

Contact Info

Product

Resources

About