SIRT1 Promotes Osteogenic Differentiation in Human Dental Pulp Stem Cells through Counteracting the Activation of STAT3

Human dental pulp stem cells (hDPSCs), which are characterized by self-renewal capacity and the ability of multilineage differentiation, have gained increased attention in regenerative medicine recently. Histone acetylation modulator proteins (HAMPs) are a protein family that mediates the modification and identification of histone acetylation and participates in various critical cellular processes. Here, we comprehensively surveyed the expression profile of HAMPs during osteoblast differentiation of hDPSCs and found that the HDAC class III pathway was upregulated, whereas the signal transducer and activator of transcription 3 (STAT3) signaling was downregulated during osteogenesis. Further laboratory research demonstrated that Sirtuin-1 (SIRT1), a class III HDAC, was upregulated and STAT3 activation was downregulated during osteogenic differentiation. SIRT1 counteracted the activation of STAT3 to promote osteogenic differentiation of hDPSCs at 7 and 21 days in both Western blot assay and chemical staining, which highlights the promising utility of SIRT1 activators in hDPSCs-based therapies for bone augmentation strategies and provides clinical insights that may lead to the development of osteogenic agents.

Automated summary

The study reveals that during osteoblast differentiation of hDPSCs, the HDAC class III pathway is upregulated while STAT3 signaling is downregulated. SIRT1, a class III HDAC, counteracts STAT3 activation to promote osteogenic differentiation of hDPSCs. This research highlights the potential use of SIRT1 activators in hDPSC-based therapies for bone augmentation strategies.