PMID- 38169761
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240105
IS  - 2405-8440 (Print)
IS  - 2405-8440 (Electronic)
IS  - 2405-8440 (Linking)
VI  - 10
IP  - 1
DP  - 2024 Jan 15
TI  - Activation of wnt/beta-catenin signaling pathway down regulated osteogenic 
      differentiation of bone marrow-derived stem cells in an anhidrotic ectodermal 
      dysplasia patient with EDA/EDAR/EDARADD mutation.
PG  - e23057
LID - 10.1016/j.heliyon.2023.e23057 [doi]
LID - e23057
AB  - OBJECTIVE: To explore the mechanism by which the Wnt/beta-catenin pathway induces 
      osteogenic differentiation of bone marrow-derived stem cells (BMSCs) in 
      anhidrotic ectodermal dysplasia (AED) with an Ectodysplasin A (EDA)/EDA receptor 
      (EDAR)/EDARADD mutation. METHODS: An AED patient served as the AED group, whereas 
      the other patients without AED were included in the normal group. Peripheral 
      venous blood collected from the AED patient was subjected to whole-genome 
      resequencing. BMSCs from the mandible of patients with AED and normal individuals 
      were isolated and cultured in vitro. Cell proliferation assay was performed to 
      compare the growth speed of BMSCs between the AED and normal groups. CHIR-99021, 
      an activator of the Wnt/beta-catenin pathway and XAV-939, an inhibitor, was used to 
      manage BMSCs in an osteogenic environment in both groups. The expression of 
      beta-catenin was detected by quantitative polymerase chain reaction, while that of 
      RUNX2 was detected by western blotting. Alizarin red was used for staining. 
      RESULTS: A novel mutation (c.152T > A in EDA) and two known mutations 
      (c.1109T > C in EDAR and c.27G > A in EDARADD) were identified. The growth rate 
      in the normal group was higher than that in the AED group. In the normal group, 
      the number and size of calcified nodes and the expression of RUNX-2 increased 
      with CHIR-99021 treatment, which could be inhibited by XAV-939. In contrast, 
      CHIR-99021 inhibited osteogenesis in the AED group and this effect was promoted 
      by XAV-939. CONCLUSION: Activation of the Wnt/beta-catenin pathway downregulates 
      osteogenesis of BMSCs in AED patients with EDA/EDAR/EDARADD gene mutations. 
      Further investigation in more AED patients is required, given the wide range of 
      mutations involved in AED.
CI  - (c) 2023 The Authors. Published by Elsevier Ltd.
FAU - Bao, Dong-Yu
AU  - Bao DY
AD  - Department of Stomatology, the Affiliated Drum Tower Hospital of Nanjing 
      University Medical School. 321 Zhongshan Road, Nanjing, 210008, China.
AD  - Department of Dental Implantology, Nanjing Stomatological Hospital, Medical 
      School of Nanjing University, No.30 Zhongyang Road, Nanjing, 210008, China.
FAU - Yang, Yun
AU  - Yang Y
AD  - Department of Stomatology, the Affiliated Drum Tower Hospital of Nanjing 
      University Medical School. 321 Zhongshan Road, Nanjing, 210008, China.
FAU - Tong, Xin
AU  - Tong X
AD  - Department of Dental Implantology, Nanjing Stomatological Hospital, Medical 
      School of Nanjing University, No.30 Zhongyang Road, Nanjing, 210008, China.
FAU - Qin, Hai-Yan
AU  - Qin HY
AD  - Department of Stomatology, the Affiliated Drum Tower Hospital of Nanjing 
      University Medical School. 321 Zhongshan Road, Nanjing, 210008, China.
LA  - eng
PT  - Journal Article
DEP - 20231209
PL  - England
TA  - Heliyon
JT  - Heliyon
JID - 101672560
PMC - PMC10758735
OTO - NOTNLM
OT  - Ectodermal dysplasia
OT  - Mesenchymal stem cell
OT  - Osteogenesis
OT  - Wnt/beta-Catenin pathway
COIS- The authors declare that they have no known competing financial interests or 
      personal relationships that could have appeared to influence the work reported in 
      this paper.
EDAT- 2024/01/04 01:18
MHDA- 2024/01/04 01:19
PMCR- 2023/12/09
CRDT- 2024/01/03 12:02
PHST- 2022/12/30 00:00 [received]
PHST- 2023/10/29 00:00 [revised]
PHST- 2023/11/24 00:00 [accepted]
PHST- 2024/01/04 01:19 [medline]
PHST- 2024/01/04 01:18 [pubmed]
PHST- 2024/01/03 12:02 [entrez]
PHST- 2023/12/09 00:00 [pmc-release]
AID - S2405-8440(23)10265-9 [pii]
AID - e23057 [pii]
AID - 10.1016/j.heliyon.2023.e23057 [doi]
PST - epublish
SO  - Heliyon. 2023 Dec 9;10(1):e23057. doi: 10.1016/j.heliyon.2023.e23057. eCollection 
      2024 Jan 15.