WISP-1 Induced by Mechanical Stress Contributes to the Fibrosis and Hypertrophy of Ligamentum Flavum via the Hedgehog-Gli1 Signaling

The study investigated the role of WISP-1 in the fibrosis and hypertrophy of ligamentum flavum (LF), which contributes to lumbar spinal canal stenosis. It was found that mechanical stress increased WISP-1 expression in LF fibroblasts, which in turn induced fibrogenesis through the Hedgehog-Gli1 signaling pathway. The study demonstrated that Gli1 was upregulated in hypertrophic LF tissues and was necessary for fibroblast viability and collagen expression. In vivo experiments with a hypertrophic LF rabbit model confirmed these findings, showing increased expression of WISP-1, Gli1, and ɑ-SMA. The administration of cyclopamine, a Hedgehog pathway inhibitor, reduced collagen expression, fibroblast proliferation, and myofibroblast differentiation, thereby ameliorating LF fibrosis.