IL-1β contributes to the secretion of sclerostin by osteocytes and targeting sclerostin promotes spinal fusion at early stages

Abstract

Abstract Background Despite extensive research, there is still a need for safe and effective agents to promote spinal fusion. Interleukin (IL)-1β is an important factor which influences the bone repair and remodelling. The purpose of our study was to determine the effect of IL-1β on sclerostin in osteocytes and to explore whether inhibiting the secretion of sclerostin from osteocytes can promote spinal fusion at early stages. Methods Small-interfering RNA was used to suppress the secretion of sclerostin in Ocy454 cells. MC3T3-E1 cells were cocultured with Ocy454 cells. Osteogenic differentiation and mineralisation of MC3T3-E1 cells were evaluated in vitro. SOST knock-out rat generated using the CRISPR-Cas9 system and rat spinal fusion model was used in vivo. The degree of spinal fusion was assessed by manual palpation, radiographic analysis and histological analysis at 2 and 4 weeks. Results We found that IL-1β level had a positive association with sclerostin level in vivo. IL-1β promoted the expression and secretion of sclerostin in Ocy454 cells in vitro. Inhibition of IL-1β-induced secretion of sclerostin from Ocy454 cells could promote the osteogenic differentiation and mineralisation of cocultured MC3T3-E1 cells in vitro. The extent of spinal graft fusion was greater in SOST-knockout rats than in wild-type rats at 2 and 4 weeks. Conclusions The results demonstrate that IL-1β contributes to a rise in the level of sclerostin at early stages of bone healing. Suppressing sclerostin may be an important therapeutic target capable of promoting spinal fusion at early stages.

Keywords

• Sclerostin
• Spinal fusion
• Osteocyte
• Osteoblast
• IL-1β