2. Academic Validation
  3. Human dental pulp stem cells are subjected to metabolic reprogramming and repressed proliferation and migration by the sympathetic nervous system via ADRA1B

Human dental pulp stem cells are subjected to metabolic reprogramming and repressed proliferation and migration by the sympathetic nervous system via ADRA1B

  • J Endod. 2023 Sep 26:S0099-2399(23)00608-8. doi: 10.1016/j.joen.2023.09.007.
Chengcan Yang 1,  Qian Gao 1,  Nuo Xu 1,  Kai Yang 2,  Zhuan Bian 3
Affiliations

Affiliations

  • 1 The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Luoyu Road 237, Wuhan, Hubei, 430079, China.
  • 2 The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Luoyu Road 237, Wuhan, Hubei, 430079, China. Electronic address: yangkai@whu.edu.cn.
  • 3 The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Luoyu Road 237, Wuhan, Hubei, 430079, China. Electronic address: bianzhuan@whu.edu.cn.
PMID: 37769871 DOI: 10.1016/j.joen.2023.09.007
Abstract

Introduction: Human dental pulp stem cells (hDPSCs) reside in specialized microenvironments in the dental pulp, termed "niches", which are composed of diverse cellular components including nerves. Sensory nerves can positively regulate the expansion and differentiation of pulp cells, while the biological effects of the sympathetic nervous system (SNS) on hDPSCs remain elusive. This study is devoted to investigating the effects and underlying mechanisms of the SNS on the proliferation and migration of hDPSCs.

Methods: The distribution of sympathetic nerve fibers in human dental pulp was examined by immunofluorescence staining of tyrosine hydroxylase (TH). The concentration of norepinephrine (NE) in healthy and carious human dental pulp tissues was detected using ELISA. RNA-sequencing was applied to identify the dominant sympathetic neurotransmitter receptor in hDPSCs. Seahorse metabolic assay, ATP assay, lactate assay, and mtDNA copy number were performed to determine the level of glycometabolism. Transwell assay, wound healing assay, EdU staining assay, cell cycle assay, and CCK8 were conducted to analyze the migratory and proliferative capacities of hDPSCs.

Results: Sprouting of sympathetic nerve fibers and an increased concentration of NE were observed in inflammatory pulp tissues. Sympathetic nerve fibers were mainly distributed along blood vessels, and Aldehyde dehydrogenase 1 (ALDH1)-positive hDPSCs resided in close proximity to neurovascular bundles. ADRA1B was identified as the major sympathetic neurotransmitter receptor expressed in hDPSCs, and its expression was enhanced in inflammatory pulp tissues. In addition, the SNS inhibited the proliferation and migration of hDPSCs through metabolic reprogramming via ADRA1B and its crosstalk with Akt and p38 MAPK signaling pathways.

Conclusions: This study demonstrates that the SNS can shift the metabolism of hDPSCs from Oxidative Phosphorylation (OXPHOS) to anaerobic glycolysis via ADRA1B and its crosstalk with Akt and p38 MAPK signaling pathways, thereby inhibiting the proliferative and migratory abilities of hDPSCs. This metabolic shift may facilitate the maintenance of the quiescent state of hDPSCs.

Keywords

ADRA1B; Dental pulp stem cells; metabolic reprogramming; migration; proliferation; sympathetic nervous system.

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