Hypophosphatasia-associated Deficiencies in Mineralization and Gene Expression in Cultured Dental Pulp Cells Obtained from Human Teeth

Autor(es)

Rodrigues, Thaisangela L. ^[1] ; Foster, Brian L. ^[2] ; Silverio, Karina G. ^[1] ; Martins, Luciane ^[1] ; Casati, Marcio Z. ^[1] ; Sallum, Enilson A. ^[1] ; Somerman, Martha J. ^[2] ; Nociti, Jr., Francisco H. ^{[1, 2]}

Afiliação do(s) autor(es)

^[1] Univ Estadual Campinas, Sch Dent, Div Periodont, Dept Prosthodont & Periodont, Sao Paulo - Brazil

^[2] NIAMSD, Natl Inst Hlth NIAMSNIH, Bethesda, MD 20892 - USA

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF ENDODONTICS; v. 38, n. 7, p. 907-912, JUL 2012.
• Citações Web of Science: 7

Resumo

Introduction: Mutations in the gene ALPL in hypophosphatasia (HPP) reduce the function of tissue nonspecific alkaline phosphatase, and the resulting increase in pyrophosphate (PPi) contributes to bone and tooth mineralization defects by inhibiting physiologic calcium-phosphate (P-i) precipitation. Although periodontal phenotypes are well documented, pulp/dentin abnormalities have been suggested in the clinical literature although reports are variable and underlying mechanisms remains unclear. in vitro analyses were used to identify mechanisms involved in HPP-associated pulp/dentin phenotypes. Methods: Primary pulp cells cultured from HPP subjects were established to assay alkaline phosphatase (ALP) activity, mineralization, and gene expression compared with cells from healthy controls. Exogenous P-i was provided to the correct P-i/PPi ratio in cell culture. Results: HPP cells exhibited significantly reduced ALP activity (by 50%) and mineral nodule formation (by 60%) compared with the controls. The expression of PP; regulatory genes was altered in HPP pulp cells, including reduction in the progressive ankylosis gene (ANKH) and increased ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1). Odontoblast marker gene expression was disrupted in HPP cells, including reduced osteopontin (OPN), dentin matrix protein 1 (DMP1), dentin sialophosphoprotein (DSPP), and matrix extracellular phosphoprotein (MEPE). The addition of P-i provided a corrective measure for mineralization and partially rescued the expression of some genes although cells retained altered messenger RNA levels for PPi-associated genes. Conclusions: These studies suggest that under HPP conditions pulp cells have the compromised ability to mineralize and feature a disrupted odontoblast profile, providing a first step toward understanding the molecular mechanisms for dentin phenotypes observed in HPP. (J Endod 2012;38:907-912) (AU)

• Processo FAPESP: 08/00534-7 - Análise diferencial da regulação de genes associados ao metabolismo do fosfato de células da polpa e ligamento periodontal em indivíduos saudáveis e com hipofosfatasia
• Beneficiário: Márcio Zaffalon Casati
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 07/08192-5 - Análise diferencial da regulação de genes associados ao metabolismo do fosfato de células da polpa e ligamento periodontal em indivíduos saudáveis e com hipofosfatasia
• Beneficiário: Thaisângela Rodrigues Lopes e Silva Gomes
• Modalidade de apoio: Bolsas no Brasil - Doutorado