Biomechanical stress regulates mammalian tooth replacement via the integrin β1‐RUNX2‐Wnt pathway. (12th December 2019)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: EMBO journal. Volume 39:Number 3(2020)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2019-12-12
• Subjects: biomechanics -- organ replacement -- stress -- Wnt signaling; Molecular biology -- Periodicals; 572.805
• DOI: 10.15252/embj.2019102374
• Languages: English
• ISSNs: 0261-4189

Abstract

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. Synopsis: Most mammals undergo replacement of deciduous teeth with permanent dentition during the postnatal development. Here, studies in miniature pigs and human samples suggest that eruption of the deciduous tooth triggers permanent tooth primordium maturation via mechanical stress release in the mandible. Dental lamina of the permanent tooth remains in a resting state until deciduous tooth erupts. Eruption‐induced elease of mechanical stress inside the mandible activates permanent tooth initiation. Mechanical stress suppresses permanent tooth initiation via RUNX2‐mediated regulation of Wnt pathway activity. Abstract : Eruption of the deciduous tooth triggers maturation of the permanent tooth primordium via mechanical stress release in the mandible.