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

    November 2020
    Chao Sun, Hong Ma, Jian Yin, Han Zhang, Hui Liu
    Studysummary This study found that WISP-1 plays a key role in ligamentum flavum fibrosis through the Hedgehog-Gli1 pathway, with cyclopamine showing potential to reduce fibrosis effects in a rabbit model. Our plain-language summary of this paper — not a Tressless recommendation.
    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.
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