Compressive force regulates orthodontic tooth movement via activating the NLRP3 inflammasome

• Published in: The FASEB journal Vol. 36; no. 12; p. e22627
• Main Authors: Han, Yineng, Yang, Qiaolin, Huang, Yiping, Gao, Pengfei, Jia, Lingfei, Zheng, Yunfei, Li, Weiran
• Format: Journal Article
• Language: English
• Published: United States 01.12.2022
• Subjects: Animals; Inflammasomes - metabolism; Interleukin-1beta - metabolism; Macrophages - metabolism; Mice; NLR Family, Pyrin Domain-Containing 3 Protein - genetics; NLR Family, Pyrin Domain-Containing 3 Protein - metabolism; Osteoclasts - metabolism; Tooth Movement Techniques; purinergic 2X7 receptor; autophagy; NLRP3 inflammasome; mechanical force; cyclic GMP-AMP synthase
• ISSN: 1530-6860
• DOI: 10.1096/fj.202200447RR

Mechanical stress regulates various cellular functions like cell inflammation, immune responses, proliferation, and differentiation to maintain tissue homeostasis. However, the impact of mechanical signals on macrophages and the underlying mechanisms by which mechanical force regulates bone remodeling during orthodontic tooth movement remain unclear. NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome has been reported to promote osteoclastic differentiation to regulate alveolar bone resorption. But the relationship between the compressive force and NLRP3 inflammasome in macrophages remains unknown. In this study, immunohistochemical staining results showed elevated expression of NLRP3 and interleukin-1β, as well as an increased number of macrophages expressing NLRP3, on the compression side of the periodontal tissues, after force application for 7 days. Furthermore, the number of tartrate-resistant acid phosphatase-positive osteoclasts, and the mRNA and protein expression levels of osteoclast-related genes in the periodontal tissue decreased in the Nlrp3 mice compared to the WT mice group after orthodontic movement. In vitro mechanical force activates the NLRP3 inflammasome and inhibits autophagy. Intraperitoneal injection of the autophagy inhibitor 3-methyladenine in Nlrp3 mice promoted orthodontic tooth movement. This result indicates that the absence of NLRP3 inflammasome activation can be partially compensated for by autophagy inhibitors. Mechanistically, force-induced activation of the NLRP3 inflammasome in macrophages via the cGAS/P2X7R axis. In conclusion, compressive force regulates orthodontic tooth movement via activating the NLRP3 inflammasome.