Interleukin-17A promotes proliferation and osteogenic differentiation of human ligamentum flavum cells through regulation of β-catenin nuclear translocation

Abstract Thoracic ossification of the ligamentum flavum (TOLF) is the leading cause of thoracic spinal stenosis with no specifc treatment available. IL-17A has received widespread attention for its key contribution in the regulation of bone metabolism and heterotopic ossification. However, it is unclear whether IL-17A is involved in TOLF. Our results showed that IL-17A expression was elevated in ossified ligamentum flavum tissue compared to normal ligamentum flavum. In in vitro experiments, IL-17A stimulation promoted the proliferation and osteogenic differentiation of ligamentum flavum cells (LFCs) derived from TOLF patients. Mechanistically, we found that IL-17A stimulation promoted nuclear translocation of β-catenin, whereas silencing of β-catenin attenuated IL-17A-induced proliferation and osteogenic differentiation of LFCs. Furthermore, co-culture of T helper 17 (Th17) cells with LFCs showed that IL-17A secreted by Th17 cells significantly enhanced the accumulation of β-catenin in the nucleus, as well as the proliferation and osteogenic differentiation of LFCs. However, these effects were markedly attenuated after the neutralization of IL-17A. Our study demonstrates that IL-17A secreted by Th17 cells in the lesion microenvironment may be involved in TOLF by regulating nuclear translocation of β-catenin to promote proliferation and osteogenic differentiation of LFCs. This study helps to elucidate the pathological mechanism of TOLF and suggests the possibility of IL-17A as a potential target for the prevention and treatment of TOLF.