YAP Deficiency in Gli1+ Osteogenic Progenitors Leads to Condylar Hypoplasia via β-Catenin Signaling.

OBJECTIVES

The pathogenesis of mandibular condylar hypoplasia has not been fully understood. Our previous studies provided evidence that Gli1+ osteogenic progenitors contribute to condylar development. This study aimed to investigate the role of YAP in Gli1+ cells during condylar development.

METHODS

We generated Gli1-CreERT2;Yapfl/fl mice, in which tamoxifen (TMX) was used to induce the deletion of Yap in Gli1+ cells. CHIR injection was to activate β-catenin signaling. Microscopic photography, Micro-CT, hematoxylin-eosin (H&E) staining, immunofluorescence (IF) staining, Real-time quantitative polymerase chain reaction (RT-qPCR), tartrate-resistant acid phosphatase (TRAP) staining and calcein-alizarin red double labeling were conducted for analyses. Chromatin immunoprecipitation (ChIP) assay was used to investigate the molecular mechanism involved.

RESULTS

YAP co-localized with mandibular condylar Gli1+ osteogenic progenitors. After induction, Gli1-CreERT2;Yapfl/fl mice suffered from condylar hypoplasia characterized by reduced bone mass and impaired osteogenesis due to decreased cell proliferation. ChIP-qPCR analysis, RT-qPCR analysis, and immunofluorescence staining further proved that YAP could directly regulate the expression of β-catenin. Functionally, pharmacological activation of β-catenin signaling successfully alleviated condylar hypoplasia in Gli1-CreERT2;Yapfl/fl mice.

CONCLUSIONS

Our study demonstrated that the YAP/β-catenin axis mediated osteogenesis in Gli1+ osteogenic progenitors during condylar development, which may provide a potential target for the treatment of condylar hypoplasia.