Signalling Pathways and Mechanical Forces Interact in Craniofacial Development and Homeostasis

Craniofacial bones, as essential components of the human head, play a crucial role in both physiological function and morphological evolution through their development and the maintenance of homeostasis. Unlike skeletal bones of the trunk, which originate from the mesoderm, craniofacial bones originate from the ectodermal neural crest, presenting challenges in directly applying findings from long bone studies. Their development occurs via intramembranous ossification, endochondral ossification, and specialized osteogenic patterns, and is co-regulated by both mechanical forces and molecular signalling pathways. The imbalances in these biomechanical regulatory mechanisms contribute to disruptions in craniofacial bone homeostasis, which can result in a range of developmental and acquired skeletal disorders. This review highlights recent advances in the molecular regulation of craniofacial bone development, examines the interplay between mechanical and genetic regulatory mechanisms, and discusses diseases associated with imbalances in craniofacial bone homeostasis, offering novel insights for the prevention and treatment of craniofacial bone disorders.