Wnt pathway inhibitors are upregulated in XLH dental pulp cells in response to odontogenic differentiation

Abstract

X-linked hypophosphatemia (XLH) represents the most common form of familial hypophosphatemia. Although significant advances have been made in the treatment of bone pathology, patients undergoing therapy continue to experience significantly decreased oral health-related quality of life. The following study addresses this persistent oral disease by further investigating the effect of DMP1 expression on the differentiation of XLH dental pulp cells. Dental pulp cells were isolated from the third molars of XLH and healthy controls and stable transduction of full-length human DMP1 were achieved. RNA sequencing was performed to evaluate the genetic changes following the induction of odontogenic differentiation. RNAseq data shows the upregulation of inhibitors of the canonical Wnt pathway in XLH cells, while constitutive expression of full-length DMP1 in XLH cells reversed this effect during odontogenic differentiation. These results imply that inhibition of the canonical Wnt pathway may contribute to the pathophysiology of XLH and suggest a new therapeutic strategy for the management of oral disease.

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Funding

U.S. Department of Health & Human Services | NIH | National Institute of Dental and Craniofacial Research (NIDCR)(DE011657, DE028193, DE018381, DE018381, DE028193); U.S. Department of Health & Human Services | NIH | National Institute of Dental and Craniofacial Research (NIDCR); U.S. Department of Health & Human Services | NIH | National Institute of Dental and Craniofacial Research (NIDCR); Brodie Endowment Fund, UIC funding.; U.S. Department of Health & Human Services | NIH | National Institute of Dental and Craniofacial Research (NIDCR); U.S. Department of Health & Human Services | NIH | National Institute of Dental and Craniofacial Research (NIDCR)