The Role of NLRP3 Inflammasome Activities in Bone Diseases and Vascular Calcification
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REVIEW
The Role of NLRP3 Inflammasome Activities in Bone Diseases and Vascular Calcification Chenyang Yu ,1,2 Caihua Zhang,1,2 Zhihui Kuang,1,2 and Qiang Zheng
1,2,3
Received July 21, 2020; accepted October 2, 2020
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 pathogenrelated 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.
Abstract—
KEY WORDS: inflammation; NLRP3 inflammasome; bone remodeling; osteolysis; vascular calcification.
INTRODUCTION Inflammasomes play a vital role in inflammatory responses. They activate immune responses by releasing cytokines and inducing pyroptosis [1, 2]. The NOD, LRR, and pyrin domain-containing protein 3 (NLRP3) is an essential inflammasome of immune Chenyang Yu and Caihua Zhang contributed equally to this work. 1
Department of Orthopedic Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, No. 88, Jiefang Road, Hangzhou, 310009, China 2 Orthopedics Research Institute of Zhejiang University, No. 88, Jiefang Road, Hangzhou, 310009, China 3 To whom correspondence should be addressed at Orthopedics Research Institute of Zhejiang University, No. 88, Jiefang Road, Hangzhou, 310009, China. E-mail: [email protected]
response and can be activated by various stimuli [3]. The inflammasome contains NLRP3, apoptosisassociated speck-like protein containing a CARD (ASC) and pro-caspase-1 [4]. Activated NLRP3 can cleave pro-caspase-1 into p20 and p10 subunits, inducing the maturation and release of proinflammatory cytokines such as interleukin-1β (proIL-1β) and IL-18 [5]. IL-1β can induce secretion of RANKL (receptor activator of NF-κB ligand) and activate osteoclasts, causing a series of inflammatory responses [6]. Activated caspase-1 specifically recognizes and cleaves gasdermin D (GSDMD) causing cell pyroptosis [7, 8]. It is currently believed that both pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) can activate the innate immune system
0360-3997/20/0000-0001/0 # 2020 The Author(s)
Yu, Zhang, Kuang, and Zheng and inflamma
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