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Biomechanical stress regulates mammalian tooth replacement via the integrin β1‐RUNX2‐Wnt pathway
Author(s) -
Wu Xiaoshan,
Hu Jinrong,
Li Guoqing,
Li Yan,
Li Yang,
Zhang Jing,
Wang Fu,
Li Ang,
Hu Lei,
Fan Zhipeng,
Lü Shouqin,
Ding Gang,
Zhang Chunmei,
Wang Jinsong,
Long Mian,
Wang Songlin
Publication year - 2019
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.2019102374
Subject(s) - biology , wnt signaling pathway , runx2 , microbiology and biotechnology , integrin , signal transduction , beta catenin , transcription factor , genetics , cell , gene
Abstract 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.