A novel WNT10A variant impairs the homeostasis of alveolar bone mesenchymal stem cells

Author:

Lin Bichen1,Liu Haochen2ORCID,Liu Hangbo2,Su Lanxin2,Sun Kai2,Feng Hailan2ORCID,Liu Yang2,Yu Miao2ORCID,Han Dong2ORCID

Affiliation:

1. Frist Clinical Division Peking University School and Hospital of Stomatology & National Center of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices Beijing China

2. Department of Prosthodontics Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices Beijing China

Abstract

AbstractObjectivesTo explore the influence of a novel WNT10A variant on bone mineral density, proliferation, and osteogenic differentiation capacities of alveolar bone mesenchymal stem cells in humans.Subjects and MethodsWhole‐exome sequencing and Sanger sequencing were utilized to detect gene variants in a family with non‐syndromic tooth agenesis (NSTA). The panoramic mandibular index was calculated on the proband with WNT10A variant and normal controls to evaluate bone mineral density. Alveolar bone mesenchymal stem cells from the proband with a novel WNT10A variant and normal controls were isolated and cultured, then proliferation and osteogenic differentiation capacities were evaluated and compared.ResultsWe identified a novel WNT10A pathogenic missense variant (c.353A > G/p. Tyr118Cys) in a family with NSTA. The panoramic mandibular index of the proband implied a reduction in bone mineral density. Moreover, the proliferation and osteogenic differentiation capacities of alveolar bone mesenchymal stem cells from the proband with WNT10A Tyr118Cys variant were significantly decreased.ConclusionsOur findings broaden the spectrum of WNT10A variants in patients with non‐syndromic oligodontia, suggest an association between WNT10A and the proliferation and osteogenic differentiation of alveolar bone mesenchymal stem cells, and demonstrate that WNT10A is involved in maintaining jaw bone homeostasis.

Funder

National Natural Science Foundation of China

Publisher

Wiley

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