Wang Y, Lee B H, Yang Z, Ho T J, Ci H, Jackson B, Punshon T, Wang B, Levy J, Ho S P
Department of Preventive and Restorative Dental Sciences, School of Dentistry, University of California, San Francisco, CA, USA.
State Key Laboratory of Structural Analysis for Industrial Equipment, Department of Engineering Mechanics, Dalian University of Technology, Dalian, China.
J Dent Res. 2025 Apr;104(4):398-407. doi: 10.1177/00220345241294001. Epub 2025 Jan 28.
The upstream mechanobiological pathways that regulate the downstream mineralization rates in periodontal tissues are limitedly understood. Herein, we spatially colocalized and correlated compression and tension strain profiles with the expressions of mechanosensory ion channels (MS-ion) TRPV4 and PIEZO1, biometal zinc, mitochondrial function marker (), cell senescence indicator (), and oxygen status marker hypoxia-inducible factor-1α () in rats fed hard and soft foods. The observed zinc and related cellular homeostasis in vivo were ascertained by TRPV4 and PIEZO1 agonists and antagonists on human periodontal ligament fibroblasts ex vivo. Four-week-old male Sprague-Dawley rats were fed hard ( = 3) or soft ( = 3) foods for 4 wk (in vivo). Significant changes in alveolar socket and root shapes with decreased periodontal ligament space and increased cementum volume fraction were observed in maxillae on reduced loads (soft food). Reduced loads impaired distally localized compression-stimulated PIEZO1 and mesially localized tension-stimulated TRPV4, decreased mitochondrial function (), and increased cell senescence in mesial and distal periodontal regions. The switch in from hard food-distal to soft food-mesial indicated a plausible effect of shear-regulated blood and oxygen flows in the periodontal complex. Blunting or activating TRPV4 or PIEZO1 MS-ion channels by channel-specific antagonists or agonists in human periodontal ligament fibroblast cultures (in vitro) indicated a positive correlation between zinc levels and zinc transporters but not with MS-ion channel expressions. The effects of reduced chewing loads in vivo were analogous to TRPV4 and PIEZO1 antagonists in vitro. Study results collectively illustrated that tension-induced TRPV4 and compression-induced PIEZO1 activations are necessary for cell metabolism. An increased hypoxic state with reduced functional loads can be a conducive environment for cementum growth. From a practical standpoint, dose rate-controlled loads can modulate tension and compression-specific MS-ion channel activation, cellular zinc, and transcription. These mechanobiochemical events indicate the plausible catalytic role of biometal zinc in mineralization, periodontal maintenance, and dentoalveolar joint function.
调节牙周组织下游矿化速率的上游机械生物学途径目前了解有限。在此，我们在喂食硬食和软食的大鼠中，将压缩和拉伸应变曲线与机械感觉离子通道（MS-离子）TRPV4和PIEZO1、生物金属锌、线粒体功能标志物（）、细胞衰老指标（）以及氧状态标志物缺氧诱导因子-1α（）的表达进行了空间共定位和相关性分析。通过TRPV4和PIEZO1激动剂和拮抗剂对人牙周膜成纤维细胞进行体外实验，确定了体内观察到的锌及相关细胞内稳态。4周龄雄性Sprague-Dawley大鼠分别喂食硬食（ = 3）或软食（ = 3）4周（体内实验）。在降低负荷（软食）的情况下，上颌骨的牙槽窝和牙根形状发生显著变化，牙周膜间隙减小，牙骨质体积分数增加。负荷降低会损害远端局部压缩刺激的PIEZO1和近中局部拉伸刺激的TRPV4，降低线粒体功能（），并增加近中和远端牙周区域的细胞衰老。从硬食远端到软食近中的转变表明，剪切调节的血液和氧流动在牙周复合体中可能具有一定作用。在人牙周膜成纤维细胞培养物（体外实验）中，通过通道特异性拮抗剂或激动剂钝化或激活TRPV4或PIEZO1 MS-离子通道，结果表明锌水平与锌转运体之间呈正相关，但与MS-离子通道表达无关。体内咀嚼负荷降低的影响与体外TRPV4和PIEZO1拮抗剂类似。研究结果共同表明，拉伸诱导的TRPV4激活和压缩诱导的PIEZO1激活对细胞代谢是必需的。功能负荷降低导致的缺氧状态增加可能是有利于牙骨质生长的环境。从实际角度来看，剂量率控制的负荷可以调节拉伸和压缩特异性MS-离子通道激活、细胞锌含量以及转录。这些机械生物化学事件表明生物金属锌在矿化、牙周维持和牙-牙槽关节功能中可能具有催化作用。
