NLRP3 Inflammasome: A New Target for Prevention and Control of Osteoporosis?

Jiang, Na; An, Jinyang; Yang, Kuan; Liu, Jinjin; Guan, Conghui; Ma, Chengxu; Tang, Xulei

doi:10.3389/fendo.2021.752546

Cited by 53 publications

(49 citation statements)

References 75 publications

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“…As a result, disruption in either hematopoiesis or vascularization should undoubtedly impact osteoclastogenesis ( Buettmann et al, 2019 ). Although our mechanistic studies revolved around myeloid cells from which the osteoclasts arise, it is worth noting that the inflammasome-GSDM pathways are functional in the osteoblast lineage ( Zhang and Wei, 2021b ; Lei et al, 2021 ; Jiang et al, 2021 ). Therefore, osteoblast lineage autonomous actions of these pathways in bone healing cannot be ruled out.…”

Section: Discussionmentioning

confidence: 99%

Fracture healing is delayed in the absence of gasdermin-interleukin-1 signaling

Sun

Chün²,

Xiao³

et al. 2022

eLife

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IL-18. Excessive GSDM-mediated pore formation can compromise the integrity of the plasma membrane thereby causing the lytic inflammatory cell death, pyroptosis. We found that GSDMD and GSDME were the only GSDMs that were readily expressed in bone microenvironment. Therefore, we tested the hypothesis that GSDMD and GSDME are implicated in fracture healing owing to their role in the obligatory inflammatory response following injury. We found that bone callus volume and biomechanical properties of injured bones were significantly reduced in mice lacking either GSDM compared with wild-type (WT) mice, indicating that fracture healing was compromised in mutant mice. However, compound loss of GSDMD and GSDME did not exacerbate the outcomes, suggesting shared actions of both GSDMs in fracture healing. Mechanistically, bone injury induced IL-1β and IL-18 secretion in vivo, a response that was mimicked in vitro by bone debris and ATP, which function as inflammatory danger signals. Importantly, the secretion of these cytokines was attenuated in conditions of GSDMD deficiency. Finally, deletion of IL-1 receptor reproduced the phenotype of Gsdmd or Gsdme deficient mice, implying that inflammatory responses induced by the GSDM-IL-1 axis promote bone healing after fracture.

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Section: Discussionmentioning

confidence: 99%

Fracture healing is delayed in the absence of gasdermin-interleukin-1 signaling

Sun

Chün²,

Xiao³

et al. 2022

eLife

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“…Additionally, biological processes involving the regulation of inflammatory response, oxidative stress, and bone homeostasis make a key role in KP treating SOP, as demonstrated in Figure 3(b) . In recent years, reports have revealed that inflammatory response plays an important role in the pathogenesis of SOP, which could disrupt bone homeostasis by accelerating bone resorption and inhibiting bone formation, thereby triggering SOP [ 47 ]. Mounting evidence reveals the role of KP in attenuating inflammatory response by encumbering the expressions of inflammatory mediators in many signaling pathways like MAPK [ 48 ].…”

Section: Discussionmentioning

confidence: 99%

Research on the Mechanism of Kaempferol for Treating Senile Osteoporosis by Network Pharmacology and Molecular Docking

Tang

Zhang

Zhao

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Kaempferol (KP), as a natural anti-inflammatory compound, has been reported to have curative effects on alleviating senile osteoporosis (SOP), which is an inflammation-related musculoskeletal disease, but the molecular mechanisms remain unclear due to scanty relevant studies. We predicted the targets of KP and SOP, and the common targets of them were subsequently used to carry out PPI analysis. Moreover, we adopted GO and KEGG enrichment analysis and molecular docking to explore potential mechanisms of KP against SOP. There were totally 152 KP-related targets and 978 SOP-related targets, and their overlapped targets comprised 68 intersection targets. GO enrichment analysis showed 1529 biological processes ( p < 0.05 ), which involved regulation of inflammatory response, oxidative stress, regulation of bone resorption and remodeling, osteoblast and osteoclast differentiation, etc. Moreover, KEGG analysis revealed 146 items including 44 signaling pathways ( p < 0.05 ), which were closely linked to TNF, IL-17, NF-kappa B, PI3K-Akt, MAPK, estrogen, p53, prolactin, VEGF, and HIF-1 signaling pathways. By means of molecular docking, we found that kaempferol is bound with the key targets’ active pockets through some connections such as hydrogen bond, pi-alkyl, pi-sigma, pi-pi Stacked, pi-pi T-shaped, and van der Waals, illustrating that kaempferol has close combination with the key targets. Collectively, various targets and pathways involve in the process of kaempferol treatment against SOP through regulating inflammatory response, oxidative stress, bone homeostasis, etc. Moreover, our study first reported that kaempferol may regulate core targets’ expression with involvement of inflammatory response, oxidative stress, and bone homeostasis, thus treating SOP.

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“…Activation of the NLRP3 inflammasome in macrophages due to P. gingivalis infection or related to bisphosphonate therapy may also lead to bone loss due to increased IL-1β production [ 128 , 129 ]. Aging, estrogen deficiency, or hyperparathyroidism provide a chronic inflammatory microenvironment and enhance NLRP3 activation, which can further lead to bone resorption and genesis of osteoporosis [ 254 , 255 , 256 , 257 ].…”

Section: The Alveolar Bonementioning

confidence: 99%

Nrf2 in the Field of Dentistry with Special Attention to NLRP3

et al. 2022

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The aim of this review article was to summarize the functional implications of the nuclear factor E2-related factor or nuclear factor (erythroid-derived 2)-like 2 (Nrf2), with special attention to the NACHT (nucleotide-binding oligomerization), LRR (leucine-rich repeat), and PYD (pyrin domain) domains-containing protein 3 (NLRP3) inflammasome in the field of dentistry. NLRP3 plays a crucial role in the progression of inflammatory and adaptive immune responses throughout the body. It is already known that this inflammasome is a key regulator of several systemic diseases. The initiation and activation of NLRP3 starts with the oral microbiome and its association with the pathogenesis and progression of several oral diseases, including periodontitis, periapical periodontitis, and oral squamous cell carcinoma (OSCC). The possible role of the inflammasome in oral disease conditions may involve the aberrant regulation of various response mechanisms, not only in the mouth but in the whole body. Understanding the cellular and molecular biology of the NLRP3 inflammasome and its relationship to Nrf2 is necessary for the rationale when suggesting it as a potential therapeutic target for treatment and prevention of oral inflammatory and immunological disorders. In this review, we highlighted the current knowledge about NLRP3, its likely role in the pathogenesis of various inflammatory oral processes, and its crosstalk with Nrf2, which might offer future possibilities for disease prevention and targeted therapy in the field of dentistry and oral health.

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NLRP3 Inflammasome: A New Target for Prevention and Control of Osteoporosis?

Cited by 53 publications

References 75 publications

Fracture healing is delayed in the absence of gasdermin-interleukin-1 signaling

Fracture healing is delayed in the absence of gasdermin-interleukin-1 signaling

Research on the Mechanism of Kaempferol for Treating Senile Osteoporosis by Network Pharmacology and Molecular Docking

Nrf2 in the Field of Dentistry with Special Attention to NLRP3

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