Distraction force promotes the osteogenic differentiation of Gli1 + cells in facial sutures via primary cilia-mediated Hedgehog signaling pathway.

Background: Trans-sutural distraction osteogenesis (TSDO) involves the application of distraction force to facial sutures to stimulate osteogenesis. Gli1 ⁺ cells in the cranial sutures play an important role in bone growth. However, whether Gli1 ⁺ cells in facial sutures differentiate into bone under distraction force is unknown.
Methods: 4-week-old Gli1ER/Td and C57BL/6 mice were used to establish a TSDO model to explore osteogenesis of zygomaticomaxillary sutures. A Gli1 ⁺ cell lineage tracing model was used to observe the distribution of Gli1 ⁺ cells and explore the role of Gli1 ⁺ cells in facial bone remodeling.
Results: Distraction force promoted bone remodeling during TSDO. Fluorescence and two-photon scanning images revealed the distribution of Gli1 ⁺ cells. Under distraction force, Gli1-lineage cells proliferated significantly and co-localized with Runx2 ⁺ cells. Hedgehog signaling was upregulated in Gli1 ⁺ cells. Inhibition of Hedgehog signaling suppresses the proliferation and osteogenesis of Gli1 ⁺ cells induced by distraction force. Subsequently, the stem cell characteristics of Gli1 ⁺ cells were identified. Cell-stretching experiments verified that mechanical force promoted the osteogenic differentiation of Gli1 ⁺ cells through Hh signaling. Furthermore, immunofluorescence staining and RT-qPCR experiments demonstrated that the primary cilia in Gli1 ⁺ cells exhibit Hedgehog-independent mechanosensitivity, which was required for the osteogenic differentiation induced by mechanical force.
Conclusions: Our study indicates that the primary cilia of Gli1 ⁺ cells sense mechanical stimuli, mediate Hedgehog signaling activation, and promote the osteogenic differentiation of Gli1 ⁺ cells in zygomaticomaxillary sutures.
(© 2024. The Author(s).)