Renewal of integumentary organs occurs cyclically throughout an organism's lifetime, but the mechanism that initiates each cycle remains largely unknown. In a miniature pig model of tooth development that resembles tooth development in humans, the permanent tooth did not begin transitioning from the resting to the initiation stage until the deciduous tooth began to erupt. This eruption released the accumulated mechanical stress inside the mandible. Mechanical stress prevented permanent tooth development by regulating expression and activity of the integrin β1-ERK1-RUNX2 axis in the surrounding mesenchyme. We observed similar molecular expression patterns in human tooth germs. Importantly, the release of biomechanical stress induced downregulation of RUNX2-wingless/integrated (Wnt) signaling in the mesenchyme between the deciduous and permanent tooth and upregulation of Wnt signaling in the epithelium of the permanent tooth, triggering initiation of its development. Consequently, our findings identified biomechanical stress-associated Wnt modulation as a critical initiator of organ renewal, possibly shedding light on the mechanisms of integumentary organ regeneration.

中文翻译：

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生物力学应力通过整联蛋白β1-RUNX2-Wnt途径调节哺乳动物的牙齿替换。

在生物的整个生命周期中，外皮器官的更新都是周期性发生的，但是启动每个循环的机制在很大程度上仍然未知。在类似于人类牙齿发育的微型猪牙齿发育模型中，直到乳齿开始萌出，恒齿才开始从静止阶段过渡到萌芽阶段。这种喷发释放了下颌骨内部累积的机械应力。机械应力通过调节周围间充质中整联蛋白β1-ERK1-RUNX2轴的表达和活性来防止恒牙生长。我们观察到人类牙胚中类似的分子表达模式。重要的，生物力学应力的释放诱导了乳齿和恒齿之间的间质中RUNX2无翼/整合（Wnt）信号的下调，以及恒齿上皮中Wnt信号的上调，触发了其发展的开始。因此，我们的发现确定了与生物力学应力相关的Wnt调节是器官更新的关键引发剂，可能有助于阐明外皮器官再生的机制。