Biomechanical stress regulates mammalian tooth replacement via the integrin β1‐RUNX2‐Wnt pathway

• Xiaoshan Wu ^[1] ; Jinrong Hu ^[2] ; Guoqing Li ^[1] ; Yan Li ^[1] ; Yang Li ^[1] ; Jing Zhang ^[1] ; Fu Wang ^[3] ; Ang Li ^[1] ; Lei Hu ^[1] ; Zhipeng Fan ^[1] ; Shouqin Lü ^[2] ; Gang Ding ^[4] ; Chunmei Zhang ^[1] ; Jinsong Wang ^[1] ; Mian Long ^[2] ; Songlin Wang ^[1]
  1. [1] Capital Medical University

     Capital Medical University

     China

     
  2. [2] 3 Center of Biomechanics and Bioengineering Key Laboratory of Microgravity (National Microgravity Laboratory) and Beijing Key Laboratory of Engineered Construction and Mechanobiology Institute of Mechanics Chinese Academy of Sciences Beijing China; 4 School of Engineering Science University of Chinese Academy of Sciences Beijing China
  3. [3] 1 Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction Capital Medical University School of Stomatology Beijing China; 6 Department of Oral Basic Science School of Stomatology Dalian Medical University Dalian China
  4. [4] 1 Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction Capital Medical University School of Stomatology Beijing China; 8 Department of Stomatology Yidu Central Hospital Weifang Medical University Weifang China

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• Localización: EMBO journal: European Molecular Biology Organization, ISSN 0261-4189, Vol. 39, Nº. 3, 2020
• Idioma: inglés
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• Resumen

  • 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.