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A Novel in vivo Gene Transfer Technique and in vitro Cell Based Assays for the Study of Bone Loss in Musculoskeletal Disorders
Published on: June 8, 2014
A Novel Inhibitor INF 39 Promotes Osteogenesis via Blocking the NLRP3/IL-1β Axis
Wenxiang Chen1, Pan Tang1, Shunwu Fan2
1Department of Orthopaedics, Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, Huzhou, Zhejiang, China.
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.

