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

Abstract 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 regenerati...

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Main Authors: Ruoshi Xu, Xiaohan Zhang, Weimin Lin, Yushun Wang, Danting Zhang, Shuang Jiang, Linfeng Liu, Jiaying Wang, Xutao Luo, Xiao Zhang, Junjun Jing, Quan Yuan, Chenchen Zhou
Format: Article
Language:English
Published: Wiley 2024-12-01
Series:Advanced Science
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Online Access:https://doi.org/10.1002/advs.202310048
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author Ruoshi Xu
Xiaohan Zhang
Weimin Lin
Yushun Wang
Danting Zhang
Shuang Jiang
Linfeng Liu
Jiaying Wang
Xutao Luo
Xiao Zhang
Junjun Jing
Quan Yuan
Chenchen Zhou
author_facet Ruoshi Xu
Xiaohan Zhang
Weimin Lin
Yushun Wang
Danting Zhang
Shuang Jiang
Linfeng Liu
Jiaying Wang
Xutao Luo
Xiao Zhang
Junjun Jing
Quan Yuan
Chenchen Zhou
author_sort Ruoshi Xu
collection DOAJ
description Abstract 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.
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spelling doaj-art-2b2c09057e8a4a5e8bf33a0ef3f09f512024-12-18T14:18:10ZengWileyAdvanced Science2198-38442024-12-011147n/an/a10.1002/advs.202310048Cathepsin K‐Positive Cell Lineage Promotes In Situ Dentin Formation Controlled by Nociceptive Sonic HedgehogRuoshi Xu0Xiaohan Zhang1Weimin Lin2Yushun Wang3Danting Zhang4Shuang Jiang5Linfeng Liu6Jiaying Wang7Xutao Luo8Xiao Zhang9Junjun Jing10Quan Yuan11Chenchen Zhou12State 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 ChinaState 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 ChinaState 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 ChinaState 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 ChinaState 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 ChinaState 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 ChinaState 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 ChinaState 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 ChinaState 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 ChinaState 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 ChinaState 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 ChinaState 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 ChinaState 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 ChinaAbstract 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.https://doi.org/10.1002/advs.202310048endodonticsgenetic mouse modelshomeostasisregenerationtranslational medicine
spellingShingle Ruoshi Xu
Xiaohan Zhang
Weimin Lin
Yushun Wang
Danting Zhang
Shuang Jiang
Linfeng Liu
Jiaying Wang
Xutao Luo
Xiao Zhang
Junjun Jing
Quan Yuan
Chenchen Zhou
Cathepsin K‐Positive Cell Lineage Promotes In Situ Dentin Formation Controlled by Nociceptive Sonic Hedgehog
Advanced Science
endodontics
genetic mouse models
homeostasis
regeneration
translational medicine
title Cathepsin K‐Positive Cell Lineage Promotes In Situ Dentin Formation Controlled by Nociceptive Sonic Hedgehog
title_full Cathepsin K‐Positive Cell Lineage Promotes In Situ Dentin Formation Controlled by Nociceptive Sonic Hedgehog
title_fullStr Cathepsin K‐Positive Cell Lineage Promotes In Situ Dentin Formation Controlled by Nociceptive Sonic Hedgehog
title_full_unstemmed Cathepsin K‐Positive Cell Lineage Promotes In Situ Dentin Formation Controlled by Nociceptive Sonic Hedgehog
title_short Cathepsin K‐Positive Cell Lineage Promotes In Situ Dentin Formation Controlled by Nociceptive Sonic Hedgehog
title_sort cathepsin k positive cell lineage promotes in situ dentin formation controlled by nociceptive sonic hedgehog
topic endodontics
genetic mouse models
homeostasis
regeneration
translational medicine
url https://doi.org/10.1002/advs.202310048
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