The Impact of NLRP3 Inflammasome on Osteoblasts and Osteogenic Differentiation: A Literature Review

Abstract

Osteoblasts (OBs), which are a crucial type of bone cells, derive from bone marrow mesenchymal stem cells (MSCs). Accumulating evidence suggests inflammatory cytokines can inhibit the differentiation and proliferation of OBs, as well as interfere with their ability to synthesize bone matrix, under inflammatory conditions. NLRP3 inflammasome is closely associated with cellular pyroptosis, which can lead to excessive release of pro-inflammatory cytokines, causing tissue damage and inflammatory responses, however, the comprehensive roles of NLRP3 inflammasome in OBs and their differentiation have not been fully elucidated, making targeting NLRP3 inflammasome approaches to treat diseases related to OBs uncertain. In this review, we provide a summary of NLRP3 inflammasome activation and its impact on OBs. We highlight the significant roles of NLRP3 inflammasome in regulating OBs differentiation and function. Furthermore, current available strategies to affect OBs function and osteogenic differentiation targeting NLRP3 inflammasome are listed and analyzed. Finally, through the prospective discussion, we seek to provide novel insights into the crucial role of NLRP3 inflammasome in diseases related to OBs and offer valuable information for devising treatment strategies.

Keywords:

• osteoblast
• pyroptosis
• NLRP3 inflammasome
• osteogenic differentiation

Abbreviations

OBs, osteoblasts; MSCs, mesenchymal stem cells; OC, osteoclasts; OP, osteoporosis; OA, osteoarthritis; OPN, osteopontin; RNUX2, runt-related transcription factor 2; PCD, programmed mode of cell death; IL, interleukin; PRRs, pattern recognition receptors; PAMPs, pathogen-associated molecular patterns; ASC, apoptosis-associated speckle-like protein; GSDMD, Gasdermin D; TLRs, toll-like receptors; LPS, lipopolysaccharide; NF-κB, nuclear factor-kappa B; PTM, post-translational modification; ALP, alkaline phosphatase; ROS, reactive oxygen species; OVX, ovariectomy; ATRA, all-trans retinoic acid; lncRMA, long non-coding RNA; miRNA, microRNA; VICs, valvular interstitial cells; ELP2, elongator complex protein 2; ART, artesunate; NAC, N-acetylcysteine; NSA, necrosulfonamide; BPA, bisphenol A; OCN, osteocalcin; CAPE, caffeic acid phenethyl ester; TCM, traditional Chinese medicine; AP/PCC, Rhizoma/Phellodendri Chinensis Cortex.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors declare no conflicts of interest in this work.

Additional information

Funding

This study was supported by the Zhejiang Provincial Natural Science Foundation of China: LY18H140001; National Natural Science Foundation of China: 81400511; Key R&D Program of Zhejiang (No 2023C03072).