The Role of NLRP3 Inflammasome Activities in Bone Diseases and Vascular Calcification

Abstract

Continuous stimulation of inflammation is harmful to tissues of an organism. Inflammatory mediators not only have an effect on metabolic and inflammatory bone diseases but also have an adverse effect on certain genetic and periodontal diseases associated with bone destruction. Inflammatory factors promote vascular calcification in various diseases. Vascular calcification is a pathological process similar to bone development, and vascular diseases play an important role in the loss of bone homeostasis. The NLRP3 inflammasome is an essential component of the natural immune system. It can recognize pathogen-related molecular patterns or host-derived dangerous signaling molecules, recruit, and activate the pro-inflammatory protease caspase-1. Activated caspase-1 cleaves the precursors of IL-1β and IL-18 to produce corresponding mature cytokines or recognizes and cleaves GSDMD to mediate cell pyroptosis. In this review, we discuss the role of NLRP3 inflammasome in bone diseases and vascular calcification caused by sterile or non-sterile inflammation and explore potential treatments to prevent bone loss.

Role of Uremic Toxins in Early Vascular Ageing and Calcification

“…Similar to IL-1β, IL-18 is produced as an inactive precursor that requires the catalytic action of inflammasome-derived caspases to produce the active molecule, hence the connection of inflammasome activation and inflammasome mediated cell death called pyroptosis with VC [ 117 ]. Initially described as an IFN-γ inducing factor as it facilitates T helper 1 (TH1) responses and natural killer (NK) cell activation, IL-18 is a member of the IL-1 family of cytokines and is mainly expressed by activated monocytes, macrophages, dendritic cells, Kupffer cells, keratinocytes, chondrocytes, synovial fibroblasts, and osteoblasts.…”

Th17 Cells in Periodontitis and Its Regulation by A20

“…IL-1b activates endothelial cells and promotes the adhesion of eosinophils, which exaggerates inflammation (214). IL-1b promotes the production of RANKL, which is vital to bone resorption as stated before (215). IL-1b also upregulates the formation and bioactivity of osteoclasts eventually leading to alveolar bone resorption (216).…”

Oral Osteomicrobiology: The Role of Oral Microbiota in Alveolar Bone Homeostasis

“…Many studies have been conducted to determine whether the NLRP3 inflammasome can be regulated by the oral microbiota. The NLRP3 inflammasome can recognize oral pathogen-associated molecular patterns and host-derived danger-signaling molecules, and activate the pro-inflammatory protease, caspase-1 ( Yu et al., 2021 ). These pathogen-associated molecular patterns include LPS, peptidoglycan, and viral double-stranded RNA ( Brown et al., 2011 ; Amari and Niehl, 2020 ).…”