Novel molecular cues for dental defects in hypophosphatasia.
Exp Cell Res
; 392(2): 112026, 2020 07 15.
Article
em En
| MEDLINE
| ID: mdl-32333908
ABSTRACT
Mineralization disorders with a broad range of etiological factors represent a huge challenge in dental diagnosis and therapy. Hypophosphatasia (HPP) belongs to the rare diseases affecting predominantly mineralized tissues, bones and teeth, and occurs due to mutations in the ALPL gene, which encodes tissue-nonspecific alkaline phosphatase (TNAP). Here we analyzed stem cells from bone marrow (BMSCs), dental pulp (DPSCs) and periodontal ligament (PDLSCs) in the absence and presence of efficient TNAP inhibitors. The differentiation capacity, expression of surface markers, and gene expression patterns of donor-matched dental cells were compared during this in vitro study. Differentiation assays showed efficient osteogenic but low adipogenic differentiation (aD) capacity of PDLSCs and DPSCs. TNAP inhibitor treatment completely abolished the mineralization process during osteogenic differentiation (oD). RNA-seq analysis in PDLSCs, comparing oD with and without TNAP inhibitor levamisole, showed clustered regulation of candidate molecular mechanisms that putatively impaired osteogenesis and mineralization, disequilibrated ECM production and turnover, and propagated inflammation. Combined alteration of cementum formation, mineralization, and elastic attachment of teeth to cementum via elastic fibers may explain dental key problems in HPP. Using this in vitro model of TNAP deficiency in DPSCs and PDLSCs, we provide novel putative target areas for research on molecular cues for specific dental problems in HPP.
Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Ligamento Periodontal
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Biomarcadores
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Doenças Estomatognáticas
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Polpa Dentária
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Células-Tronco Mesenquimais
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Hipofosfatasia
Tipo de estudo:
Etiology_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Adolescent
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Adult
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Female
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Humans
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Male
Idioma:
En
Revista:
Exp Cell Res
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Alemanha