Non-Canonical Wnt Signaling Participates in Jagged1-Induced Odonto/Osteogenic Differentiation in HDPs
Objectives: To examine the involvement of Wnt signaling in Jagged1-induced odonto/osteogenic differentiation in human dental pulp cells (hDPs) Methods: RNA sequencing data of Jagged1-treated hDPs was analyzed to identify their gene expression profile. The mRNA expression of HES1, HEY1, WNT2B, WNT5A, WNT5B, WNT16, DKK1, DKK2, and SOST was examined using real-time polymerase chain reaction. Osteogenic differentiation was determined using osteogenic-related gene expression, alkaline phosphatase (ALP) activity, and mineralization. Wnt signaling was activated using recombinant Wnt proteins, while Wnt signaling was inhibited using DKK1 or IWP-2 Results: Notch signaling activation using immobilized-Jagged1 enhanced odonto/osteogenic differentiation in hDPs as determined by increased ALP activity and mineralization. Bioinformatic analysis of the gene expression profile by high throughput RNA sequencing of the Jagged1-treated hDPs revealed that Notch regulated numerous Wnt-related genes. Among Wnt ligands, WNT2B and WNT5A mRNA levels were upregulated after Jagged1 treatment. In contrast, Wnt inhibitors, DKK1, DKK2, and SOST mRNA levels were downregulated in Jagged1-treated cells. Recombinant WNT2B and WNT5A significantly promoted in vitro mineral deposition by hDPs. The Wnt signaling inhibition experiments revealed that IWP-2, but not DKK1, inhibited Jagged1-induced ALP activity and mineralization Conclusions: The Notch ligand, Jagged1, promoted odonto/osteogenic differentiation in hDPs by regulating the non-canonical Wnt pathway
2020 South East Asia Division Meeting (Virtual) 2020 P030 Pulp Biology & Regeneration Research
Kornsuthisopon, Chatvadee
( Chulalongkorn University
, Bangkok
, Thailand
; Chulalongkorn University
, Bangkok
, Thailand
)
Manokawinchoke, Jeeranun
( Chulalongkorn University
, Bangkok
, Thailand
)
Tompkins, Kevin A.
( Chulalongkorn University
, Bangkok
, Thailand
)
Osathanon, Thanaphum
( Chulalongkorn University
, Bangkok
, Thailand
; Chulalongkorn University
, Bangkok
, Thailand
)