Xu Ruoshi, Zhang Xiaohan, Lin Weimin, Wang Yushun, Zhang Danting, Jiang Shuang, Liu Linfeng, Wang Jiaying, Luo Xutao, Zhang Xiao, Jing Junjun, Yuan Quan, Zhou Chenchen
State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China.
Adv Sci (Weinh). 2024 Dec;11(47):e2310048. doi: 10.1002/advs.202310048. Epub 2024 Oct 30.
Oral diseases affect nearly half of the global population throughout their lifetime causing pain, as estimated by the World Health Organization. Preservation of vital pulp is the therapeutic core as well as a challenge to protect natural teeth. Current bottleneck lies in that the regenerative capacity of injured pulp is undetermined. In this study, we identified a lifelong lineage that is labelled by cathepsin K (Ctsk) contributing to the physiological, reactionary and reparative odontogenesis of mouse molars. Ctsk cell-mediated dentin formation is regulated by nociceptive nerve-derived Sonic Hedgehog (Shh), especially rapidly responsive to acute injury. Notably, exogenous Shh protein to the injury pulp can preserve Ctsk cell capacity of odontogenesis for the nearby crown pulp and even remote root apex growth, alleviating conventionally developmental arrest in youth pulpitis. Exposed to chronical attrition, aged pulp Ctsk cells still hold the capacity to respond to acute stimuli and promote reparative odontogenesis, also enhanced by exogenous Shh capping. Therefore, Ctsk cells may be one of the lineages for accelerating precision medicine for efficient pulp treatment across ages. Shh application can be a candidate for vital pulp preservation and pulp injury repair by promoting regenerative odontogenesis to a certain extent from young adults to older individuals.
据世界卫生组织估计，口腔疾病在全球近一半人口的一生中都会造成疼痛。保存活髓是治疗的核心，也是保护天然牙的一项挑战。目前的瓶颈在于受伤牙髓的再生能力尚未明确。在本研究中，我们鉴定出了一条由组织蛋白酶K（Ctsk）标记的终生细胞谱系，它对小鼠磨牙的生理性、反应性和修复性牙发生均有贡献。Ctsk细胞介导的牙本质形成受伤害性神经来源的音猬因子（Shh）调控，尤其对急性损伤反应迅速。值得注意的是，向受伤牙髓外源性给予Shh蛋白可保留Ctsk细胞对附近冠髓甚至远端根尖生长的牙发生能力，缓解年轻牙髓炎中常见的发育停滞。在长期磨耗情况下，老龄牙髓Ctsk细胞仍具有对急性刺激作出反应并促进修复性牙发生的能力，外源性Shh覆盖也可增强此能力。因此，Ctsk细胞可能是加速跨年龄高效牙髓治疗精准医学的细胞谱系之一。应用Shh在一定程度上促进从年轻人到老年人的再生性牙发生，可能是活髓保存和牙髓损伤修复的一个候选方法。
