Age-associated niche remodeling drives dental pulp progenitor dysfunction and fibrosis
- 1Department of Oral Biology, Hospital of Stomatology, Jilin University, Changchun, China
- 2Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling, Jilin University, Changchun, China
- 3Department of Oral Pathology, Hospital of Stomatology, Jilin University, Changchun, China
Abstract
Dental pulp homeostasis and regeneration rely on specialized mesenchymal populations, yet aging promotes fibrotic remodeling and functional decline. Here, using the continuously growing mouse incisor as an experimentally tractable model, we integrate single-cell RNA sequencing, spatial transcriptomics, lineage tracing, and functional assays to investigate age-associated pulp remodeling. We identify a distinct Lypd1+ fibroblast progenitor population that is particularly vulnerable to age-associated dysfunction. Lineage tracing and trajectory analysis show that these cells originate from the Sfrp2hi stem cell pool, while functional studies of MACS-isolated human LYPD1+ cells provide supportive evidence for a related progenitor-like state. Notably, early aging preferentially affects Lypd1+ progenitors, rather than Sfrp2hi stem cells, promoting fibrotic conversion through aberrant upregulation of 11β-HSD2, which enhances aldosterone-mediated mineralocorticoid receptor (MR)-associated signals. Additionally, aging promotes the accumulation of Ccl4+ macrophages that establish a pro-inflammatory niche, where macrophage-derived PDGFB induces 11β-HSD2 via the P38 MAPK signaling. In vivo inhibition of the PDGF/P38/11β-HSD2 axis attenuates age-related pulp fibrosis. Together, our findings indicate that age-associated pulp fibrosis in this model is driven, at least in part, by niche-mediated metabolic reprogramming of progenitor cells rather than intrinsic stem cell exhaustion, highlighting corticosteroid metabolism as a potential therapeutic target for fibrotic degeneration in aging dental pulp.
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BibTeX
@article{yu2026ageassociated,
title = {{Age-associated niche remodeling drives dental pulp progenitor dysfunction and fibrosis}},
author = {Xiaoyi Yu and Tianmeng Sun and Mengyu Xu and Tianyuan Zhao and Huanyu Luo and Qing Zhong and Cangwei Liu and Zhengwen An},
journal = {Communications Biology},
year = {2026},
month = jul,
doi = {10.1038/s42003-026-10632-y},
url = {https://doi.org/10.1038/s42003-026-10632-y},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Age-associated niche remodeling drives dental pulp progenitor dysfunction and fibrosis
AU - Xiaoyi Yu
AU - Tianmeng Sun
AU - Mengyu Xu
AU - Tianyuan Zhao
AU - Huanyu Luo
AU - Qing Zhong
AU - Cangwei Liu
AU - Zhengwen An
PY - 2026
DA - 2026/07/07
JO - Communications Biology
DO - 10.1038/s42003-026-10632-y
UR - https://doi.org/10.1038/s42003-026-10632-y
AB - Dental pulp homeostasis and regeneration rely on specialized mesenchymal populations, yet aging promotes fibrotic remodeling and functional decline. Here, using the continuously growing mouse incisor as an experimentally tractable model, we integrate single-cell RNA sequencing, spatial transcriptomics, lineage tracing, and functional assays to investigate age-associated pulp remodeling. We identify a distinct Lypd1+ fibroblast progenitor population that is particularly vulnerable to age-associated dysfunction. Lineage tracing and trajectory analysis show that these cells originate from the Sfrp2hi stem cell pool, while functional studies of MACS-isolated human LYPD1+ cells provide supportive evidence for a related progenitor-like state. Notably, early aging preferentially affects Lypd1+ progenitors, rather than Sfrp2hi stem cells, promoting fibrotic conversion through aberrant upregulation of 11β-HSD2, which enhances aldosterone-mediated mineralocorticoid receptor (MR)-associated signals. Additionally, aging promotes the accumulation of Ccl4+ macrophages that establish a pro-inflammatory niche, where macrophage-derived PDGFB induces 11β-HSD2 via the P38 MAPK signaling. In vivo inhibition of the PDGF/P38/11β-HSD2 axis attenuates age-related pulp fibrosis. Together, our findings indicate that age-associated pulp fibrosis in this model is driven, at least in part, by niche-mediated metabolic reprogramming of progenitor cells rather than intrinsic stem cell exhaustion, highlighting corticosteroid metabolism as a potential therapeutic target for fibrotic degeneration in aging dental pulp.
SN - 2399-3642
ER -