Neutrophil extracellular traps induce the bone erosion of gout

Abstract

ObjectiveTo investigate the relationships between monosodium urate (MSU) crystals -induced neutrophil extracellular traps (NETs) and bone erosion in gout.MethodsAnimal models were used to study the relationship between NETs induced by MSU crystals and bone erosion. Neutrophils were treated with MSU crystals to induce NETs. The osteoblasts-like cells (OB) were then treated with NETs, and the supernatant was co-incubated with osteoclasts-like cells (OC). The NETs were digested with DNase, and the neutrophil elastase (NE) was inhibited with sivelestat sodium. Cell viability, mRNA, and protein expression were also assessed.ResultsAfter treating OB with NETs, the cell viability decreased. Yet, after digesting the DNA and inhibiting NE, the viability was moderately improved. The expression level of osteoprotegerin (OPG) and alkaline phosphatase (ALP) was up-regulated, while the expression level of receptor activator of nuclear factor kappa-B ligand (RANKL) was down-regulated in the sivelestat sodium + MSU group compared with MSU group. The number of OC was significantly elevated. In contrast, the number of OB was not increased in the tibia after establishing the gout model. The supernatant obtained from OB was treated with NETs promoting OC differentiation. The expression level of receptor activator of nuclear factor kappa-B (RANK), tartrate-resistant acid phosphatase (TRAP), and cathepsin K (Cst K) was up-regulated in the MSU group compared with the normal control (NC) group.ConclusionNETs induced by MSU crystals could inhibit osteoblasts viability and enhance the activity of osteoclasts.