Targeting YAP-Hhip mediated osteogenesis in Gli1+ osteogenic progenitors suppresses aberrant subchondral bone remodeling in osteoarthritis

Our findings demonstrated that YAP plays a critical role in subchondral bone remodeling. Furthermore, targeting the YAP-Hhip axis through regulation of Hh-Gli1 signaling in Gli1+ osteogenic progenitors could inhibit OA progression. This may offer new therapeutic insights for treating OA. Overall design: We generated Gli1-CreERT2;Yapfl/fl mice, in which deletion of Yap blocked the YAP signaling in the Gli1+ cell lineage. A mouse model with osteoarthritis-like changes in the temporomandibular joint (TMJ) was induced by partial discectomy (PD). Smoothened agonist administration was also used intraperitoneally after PD. Micro-CT, histological analysis, immunofluorescence staining, and RNA-seq were conducted for analyses.