Abstract
Jagged1 activates Notch signaling and subsequently promotes osteogenic differentiation in human periodontal ligament cells (hPDLs). The present study investigated the participation of the Notch receptor, NOTCH2, in the Jagged1-induced osteogenic differentiation in hPDLs. NOTCH2 and NOTCH4 mRNA expression levels increased during hPDL osteogenic differentiation. However, the endogenous NOTCH2 expression levels were markedly higher compared with NOTCH4. NOTCH2 expression knockdown using shRNA in hPDLs did not dramatically alter their proliferation or osteogenic differentiation compared with the shRNA control. After seeding on Jagged1-immobilized surfaces and maintaining the hPDLs in osteogenic medium, HES1 and HEY1 mRNA levels were markedly reduced in the shNOTCH2-transduced cells compared with the shControl group. Further, shNOTCH2-transduced cells exhibited less alkaline phosphatase enzymatic activity and in vitro mineralization than the shControl cells when exposed to Jagged1. MSX2 and COL1A1 mRNA expression after Jagged1 activation were reduced in shNOTCH2-transduced cells. Endogenous Notch signaling inhibition using a γ-secretase inhibitor (DAPT) attenuated mineralization in hPDLs. DAPT treatment significantly promoted TWIST1, but decreased ALP, mRNA expression, compared with the control. In conclusion, Notch signaling is involved in hPDL osteogenic differentiation. Moreover, NOTCH2 participates in the mechanism by which Jagged1 induced osteogenic differentiation in hPDLs.
Highlights
Jagged[1] activates Notch signaling and subsequently promotes osteogenic differentiation in human periodontal ligament cells
Notch receptors and ligands are expressed during human periodontal ligament cells (hPDLs) osteogenic differentiation. hPDLs differentiated into the osteogenic lineage when the cells were incubated in osteogenic medium (OM)
The increased expression of NOTCH2 and NOTCH4 was observed during osteogenic differentiation while NOTCH1 mRNA levels significantly decreased at day 21 compared with day 0 (Fig. 1C–F)
Summary
Jagged[1] activates Notch signaling and subsequently promotes osteogenic differentiation in human periodontal ligament cells (hPDLs). After seeding on Jagged1-immobilized surfaces and maintaining the hPDLs in osteogenic medium, HES1 and HEY1 mRNA levels were markedly reduced in the shNOTCH2-transduced cells compared with the shControl group. Endogenous Notch signaling inhibition using a γ-secretase inhibitor (DAPT) attenuated mineralization in hPDLs. DAPT treatment significantly promoted TWIST1, but decreased ALP, mRNA expression, compared with the control. Jagged[1] decreases osteoprotegerin (OPG), but not receptor activator of nuclear factor-κB ligand (RANKL), expression in human periodontal ligament cells (hPDLs)[4]. Jagged[1] immobilization activates Notch signaling and promotes osteogenic differentiation in h PDLs7,8. Jagged1-treated hPDLs exhibit increased alkaline phosphatase (ALP) enzymatic activity and an in vitro mineral deposition compared with cells in the control condition. The present study investigated the participation of NOTCH2 in Jagged-induced osteogenic differentiation in hPDLs
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