Mechanistic Role of PIEZO1 in Crouzon Syndrome: Osteogenic Regulation By FGFR2-Mutated Periosteal Progenitors at the...

Crouzon syndrome represents an autosomal dominant genetic disorder primarily characterized by craniofacial malformations. Recent advancements have enabled the successful derivation of periosteal stem cells from the periosteum, a critical reservoir of osteogenic progenitor cells. This investigation employs periosteal stem cells transfected with the C361Y-FGFR2 point mutation in conjunction with an in vitro mechanical tensile stress model to elucidate the aberrant osteogenic differentiation patterns under mechanical stimulation. The study identifies PIEZO1, a mechanosensitive ion channel protein, as a pivotal mediator in transducing extracellular mechanical signals. Through integrated analysis of PIEZO1-modulated HIPPO/YAP and BMP2/SMAD2 signaling cascades, the authors systematically evaluate the expression patterns of key regulatory nodes within these pathways. These findings establish a molecular framework for understanding defective osteogenic differentiation mechanisms in periosteal stem cells derived from Crouzon syndrome models, offering novel insights into potential therapeutic targets.