Characterization of a new target to human dental pulp regeneration through the identification of PP1 interactome

Abstract Background: Dental caries are one of the most prevalent chronic diseases worldwide affecting all age groups. Current therapeutic strategies are technically demanding and invasive procedures that only address the restoration of dental pulp. Upon damage, mineralized tissues and dental pulp are affected, activating signalling cascades that promote their repair and regeneration through stem cells differentiation into odontoblasts-like cells. Protein phosphatase 1 (PP1) participates in a panoply of cellular events, including those related with regenerative outcomes, such as odontogenic differentiation, highlighting the potential of its modulation. Methods: Here we evaluated the expression of PP1 isoforms in dental pulp cells lines. We also characterized the PP1 interactome in dental pulp and identified potential interactors involved in repair and regenerative processes. Results: The expression of all PP1 isoforms (α, β and γ) was detected in human dental cell lines. Moreover, a total of 258 proteins were identified as PP1γ regulatory interactors of protein phosphatase 1 (RIPPOs) in dental pulp, through a combination of a bioinformatic and co-immunoprecipitation/mass spectrometry analyses. Among these proteins, RRBP1 and THBS1 are promising targets, due to their roles in modulation of the regenerative response and in odontoblasts differentiation and mineralization. Conclusion: This is the first reported PP1 interactome in dental pulp that identifies potential targets to modulate PP1 activity and potentially promote dental pulp regeneration.