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WNT10A-SMOC2-LRP4 network affects permanent tooth development via potential tooth-bone interaction.

Yiqi Chen1,2, Xuechun Li1,2, Siyuan Ma1,2

  • 1Center of Stomatology and Research Center of Oral and Maxillofacial Development and Regeneration, Xiangya Hospital, Central South University, 87 Xiangya Road, City, Changsha, Province, 410008, Hunan, China.

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|December 18, 2025
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Summary
This summary is machine-generated.

Non-syndromic tooth agenesis involves permanent tooth loss. This case links variations in WNT10A, SMOC2, and LRP4 genes to tooth agenesis, suggesting mandibular bone cells influence tooth development via FGF signaling.

Keywords:
LRP4SMOC2WNT10ANon-syndromic tooth agenesis (NSTA)

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Area of Science:

  • Genetics
  • Developmental Biology
  • Oral Health

Background:

  • Non-syndromic tooth agenesis (NSTA) is characterized by permanent tooth loss.
  • The influence of the mandibular environment on NSTA is not well understood.
  • This study investigates simultaneous gene variations in NSTA.

Purpose of the Study:

  • To explore the potential impact of the mandibular environment on tooth agenesis.
  • To analyze genetic variations in WNT10A, SMOC2, and LRP4 in a patient with NSTA.
  • To investigate the signaling pathways involved in tooth development.

Main Methods:

  • Clinical examination and whole-exome sequencing of a patient with NSTA.
  • Sanger sequencing for specific gene variations.
  • Reanalysis of single-cell RNA-seq datasets and immunofluorescent staining.

Main Results:

  • The patient presented with retained primary teeth, missing permanent teeth, and abnormal mandibular bone density.
  • Novel variations in LRP4 and known variations in SMOC2 and WNT10A were identified.
  • LRP4-positive bone cells signal to WNT10A/SMOC2-positive dental pulp cells via FGF.

Conclusions:

  • Simultaneous variations in SMOC2 and a novel LRP4 variation are linked to tooth agenesis and bone development.
  • LRP4-positive alveolar bone cells may regulate tooth development through FGF signaling.
  • This signaling pathway influences WNT10A and SMOC2 in dental pulp cells.