Journal
EXPERIMENTAL CELL RESEARCH
Volume 405, Issue 2, Pages -Publisher
ELSEVIER INC
DOI: 10.1016/j.yexcr.2021.112648
Keywords
Pyroptosis; Differentiation; Osteoblasts; Necrosulfonamide; NLRP3; Caspase-1; Gasdermin D
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The study demonstrated that the pyroptosis inhibitor necrosulfonamide (NSA) promotes the proliferation and differentiation of osteoblasts by inhibiting the NLRP3/caspase-1/GSDMD pyroptosis pathway. This suggests the potential application of NSA in improving osteoblast function in fracture repair and highlights the value of the NLRP3/caspase-1/GSDMD pyroptosis pathway as a pharmaceutical target.
The acute inflammatory stimulation occurring after a bone fracture regulates the repair and healing of local bone injury; however, under certain conditions, pyroptosis may occur in osteoblasts, which affects osteoblast proliferation and differentiation, thereby affecting the growth, development and morphological changes of bone tissue. The aim of the present study was to examine the effect of the pyroptosis inhibitor necrosulfonamide (NSA) on the proliferation and differentiation of osteoblasts and elucidate the underlying mechanism. The results revealed that NSA reversed the effects of ATP/lipopolysaccharide (LPS) on cell viability and pyroptosis, and on the mRNA and protein expression of pyroptosis-related genes. It also suppressed the secretion of IL-6, TNF-alpha and IL-1 beta and reversed the effects of ATP/LPS on the activity of ALP and the mRNA expression of differentiation-related genes in osteoblasts. The fact that overexpression of caspase-1, gasdermin D (GSDMD) and NLRP3 abolished the effects of NSA on the viability and pyroptosis of osteoblasts, as well as the mRNA expression of differentiation-related genes and the activity of ALP in osteoblasts, indicated that NSA promoted the proliferation and differentiation of osteoblasts by inhibiting the NLRP3/caspase-1/GSDMD pyroptosis pathway. The present study provides proof supporting the potential application of NSA for improving the function of osteoblasts in fracture repair and indicates the value of the NLRP3/caspase-1/GSDMD pyroptosis pathway as a pharmaceutical target.
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