Cathepsin K-Positive Cell Lineage Promotes In Situ Dentin Formation Controlled by Nociceptive Sonic Hedgehog

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.