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

    Chao Sun, Qinghong Ma, Jian Yin, Han Zhang, Xinhui Liu
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    Studysummary This study found that mechanical stress activates a WISP-1/Hedgehog signaling axis that contributes to ligamentum flavum hypertrophy and fibrosis, identifying Hedgehog signaling as a potential therapeutic target.
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    The study investigated the role of WISP-1 in the fibrosis and hypertrophy of the 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. This process was confirmed in vitro and in a hypertrophic LF rabbit model. The study demonstrated that cyclopamine, a Hedgehog pathway inhibitor, reduced fibrosis-related changes, suggesting that targeting Hedgehog signaling could be a potential therapeutic approach for LF fibrosis.
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