A Novel Inhibitor INF 39 Promotes Osteogenesis via Blocking the NLRP3/IL-1 β Axis

Biomed Res Int. 2022 Jul 13:2022:7250578. doi: 10.1155/2022/7250578. eCollection 2022.

Abstract

Purpose: A balance between osteoblasts and osteoclasts is essential to maintain skeletal integrity, regulating bone metabolism and bone remodeling. The nucleotide binding oligomerization domain, leucine-rich repeat and pyrin domain containing protein 3 (NLRP3) inflammasome is known as a cytosolic complex involved in producing proinflammatory cytokines consisting of interleukin- (IL-) 1β, which accelerates the occurrence of osteoporosis. Therefore, we aimed to investigate the effect of a novel NLRP3 inhibitor INF 39 on bone formation and bone resorption. Material and Methods. Cell viability of INF 39-treated osteoclasts and calvarial osteoblasts was tested by CCK-8 assays. Quantitative RT-PCR (qRT-PCR) was used to evaluate gene expression level during osteoblast and osteoclast formation. Western blot analysis was used to determine the effect of INF 39 on osteogenic and osteoclast-related proteins.

Result: It was shown that INF 39 promotes osteoblast differentiation via inhibiting NLRP3, thereby reducing the production of IL-1β dependent on NLRP3 in vitro. However, RANKL-induced osteoclast differentiation is not influenced by INF 39 in vitro.

Conclusion: Our study suggests that NLRP3 could be a new target and INF 39 may be a potential option for prevention and treatment of osteoporosis.

MeSH terms

  • Bone Resorption* / genetics
  • Bone Resorption* / metabolism
  • Humans
  • Inflammasomes / metabolism
  • Interleukin-1beta / metabolism
  • NLR Family, Pyrin Domain-Containing 3 Protein / genetics
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
  • Osteoclasts / metabolism
  • Osteogenesis
  • Osteoporosis* / metabolism

Substances

  • Inflammasomes
  • Interleukin-1beta
  • NLR Family, Pyrin Domain-Containing 3 Protein