MEAM Seminar: “The Role of YAP and TAZ in Regulating Mechanical Load-induced Bone Adaptation and Osteocytes Mechanosensing”

Fetal movements and physical activities generate mechanical signals that regulate musculoskeletal development. It is widely accepted that a bone’s adaptive response occurs within an optimal strain range that stimulates bone formation, exceeding typical daily activity levels. This principle has led to models predicting how bones respond to mechanical loads, as insufficient mechanical signals can result in bone loss, while high signals can stimulate new bone tissue formation.
The discussions on the mechanical adaptation of tissue have primarily focused on changes in size or shape under load. However, a key question remains: how do cells sense these loads and convert them into biochemical events leading to bone gain or loss? Osteocytes, the primary mechanosensors in bone, detect mechanical and hormonal stimuli, coordinating osteoblast and osteoclast activities. Mechanical signals activate osteocyte mechanosensors, triggering pathways that regulate transcription factors like YAP (Yes-associated protein) and TAZ (Transcriptional co-activator with PDZ-binding motif). These factors induce gene expression by binding to transcription factor TEAD, directing the signaling that regulates osteoblast and osteoclast function—a process known as mechanotransduction. In this study, we hypothesize that mechanical loading regulates prenatal bone development and adult bone remodeling through YAP/TAZ signaling and osteocyte mechanosensing. Therefore our goal is to determine the roles of YAP and TAZ in mechanical load-induced prenatal and postnatal bone formation.