Shanghai Key Laboratory of Stomatology, Department of Oral and Cranio-Maxillofacial Science, Center of Craniofacial Orthodontics, National Clinical Research Center of Stomatology, Shanghai Research Institute of Stomatology, Shanghai Jiaotong University School of Medicine, , Ninth People's Hospital, Shanghai, Shanghai 200011, China.
Shanghai Key Laboratory of Stomatology, The 2 nd Dental Center, National Clinical Research Center of Stomatology, Shanghai Research Institute of Stomatology, Shanghai Jiaotong University School of Medicine, Ninth People's Hospital, Shanghai, Shanghai 200011, China.
J Bone Miner Res. 2024 May 24;39(5):580-594. doi: 10.1093/jbmr/zjae032.
Healthy alveolar bone is the cornerstone of oral function and oral treatment. Alveolar bone is highly dynamic during the entire lifespan and is affected by both systemic and local factors. Importantly, alveolar bone is subjected to unique occlusal force in daily life, and mechanical force is a powerful trigger of bone remodeling, but the effect of occlusal force in maintaining alveolar bone mass remains ambiguous. In this study, the Piezo1 channel is identified as an occlusal force sensor. Activation of Piezo1 rescues alveolar bone loss caused by a loss of occlusal force. Moreover, we identify Piezo1 as the mediator of occlusal force in osteoblasts, maintaining alveolar bone homeostasis by directly promoting osteogenesis and by sequentially regulating catabolic metabolism through Fas ligand (FasL)-induced osteoclastic apoptosis. Interestingly, Piezo1 activation also exhibits remarkable efficacy in the treatment of alveolar bone osteoporosis caused by estrogen deficiency, which is highly prevalent among middle-aged and elderly women. Promisingly, Piezo1 may serve not only as a treatment target for occlusal force loss-induced alveolar bone loss but also as a potential target for metabolic bone loss, especially in older patients.
健康的牙槽骨是口腔功能和口腔治疗的基石。牙槽骨在整个生命周期中都是高度活跃的，受到全身和局部因素的影响。重要的是，牙槽骨在日常生活中承受着独特的咬合力量，机械力是骨重建的强大触发因素，但咬合力量在维持牙槽骨量方面的作用仍不明确。在这项研究中，Piezo1 通道被确定为咬合力量传感器。Piezo1 的激活可挽救因失去咬合力量而导致的牙槽骨丢失。此外，我们确定 Piezo1 是成骨细胞中咬合力量的介导物，通过直接促进成骨作用，并通过 Fas 配体 (FasL)-诱导的破骨细胞凋亡来顺序调节分解代谢代谢，从而维持牙槽骨的内稳态。有趣的是，Piezo1 的激活在治疗由雌激素缺乏引起的牙槽骨骨质疏松症方面也表现出显著的疗效，这种骨质疏松症在中老年女性中非常普遍。有希望的是，Piezo1 不仅可以作为治疗因咬合力量丧失引起的牙槽骨丢失的靶点，也可以作为代谢性骨丢失的潜在靶点，特别是在老年患者中。
