Dexamethasone stimulates differentiation of odontoblast-like cells in human dental pulp cultures.
Regenerative dental pulp strategies require the identification of precursors able to differentiate into odontoblast-like cells that secrete reparative dentin after injury. Pericytes have the ability to give rise to osteoblasts, chondrocytes, and adipocytes, a feature that has led to the suggestion that odontoblast-like cells could derive from these perivascular cells. In order to gain new insights into this hypothesis, we investigated the effects of dexamethasone (Dex), a synthetic glucocorticoid employed to induce osteogenic differentiation in vitro, in a previously reported model of human dental pulp cultures containing pericytes as identified by their expression of smooth muscle actin (SMA) and their specific ultrastructural morphology. Our data indicated that Dex (10(-8) M) significantly inhibited cell proliferation and markedly reduced the proportion of SMA-positive cells. Conversely, Dex strongly stimulated alkaline phosphatase (ALP) activity and induced the expression of the transcript encoding the major odontoblastic marker, dentin sialophosphoprotein. Nevertheless, parathyroid hormone/parathyroid hormone-related peptide receptor, core-binding factor a1/osf 2, osteonectin, and lipoprotein lipase mRNA levels were not modified by Dex treatment. Dex also increased the proportion of cells expressing STRO-1, a marker of multipotential mesenchymal progenitor cells. These observations indicate that glucocorticoids regulate the commitment of progenitors derived from dental pulp cells to form odontoblast-like cells, while reducing the proportion of SMA-positive cells. These results provide new perspectives in deciphering the cellular and molecular mechanisms leading to reparative dentinogenesis.
INSERM EM9903, School of Dental Surgery, 1 Place Alexis Ricordeau, 44042, Cedex 1 Nantes, France.
Brigitte
B
Alliot-Licht
Gilles
G
Bluteau
David
D
Magne
Serena
S
Lopez-Cazaux
Blandine
B
Lieubeau
Guy
G
Daculsi
Jerome
J
Guicheux
D000199:Actins / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape; D002478:Cells, Cultured; D003782:Dental Pulp / Q000166:cytology*; D003907:Dexamethasone / Q000494:pharmacology*; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D009804:Odontoblasts / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism
D000199:Actins; D015415:Biomarkers; D005938:Glucocorticoids; D012333:RNA, Messenger; D003907:Dexamethasone; D000469:Alkaline Phosphatase