SIRT1 was involved in TNF-α-promoted osteogenic differentiation of human DPSCs through Wnt/β-catenin signal.

Abstract

Dental pulp stem cells (DPSCs), as one type of mesenchymal stem cells (MSCs), have the capability of self-renewal and differentiating along the various directions, including osteogenic, chondrogenic, neurogenic, and adipogenic. We previously study and found that tumor necrosis factor-α (TNF-α) promoted osteogenic differentiation of human DPSCs via the Wnt/β-catenin signaling pathway in low concentration while inhibited that in high concentration. In the abovementioned process, we found that sirtuin-1 (SIRT1) had the same change compared with the characteristic protein of bone formation, such as bone morphogenetic protein 2 (BMP2), runt-related transcription factor 2 (Runx2), and collagen I (COL1). We asked whether SIRT1 could regulate osteogenesis of DPSCs. In inflammation microenvironment constructed by TNF-α, we tested the expression changing of SIRT1 and analyzed the function of SIRT1 on osteogenic differentiation of DPSCs. SIRT1 deacetylated β-catenin, and then promote its accumulation in the nucleus. Accumulated β-catenin can lead to transcription of osteogenic characteristic genes. Using the activator of SIRT1, resveratrol, could promote the above-mentioned process of osteogenic differentiation. SIRT1 could regulate osteogenesis of DPSCs through Wnt/β-catenin signal. SIRT1, as a regulator of differentiation of DPSCs, may be a new target for cell-based therapy in oral diseases and other regenerative medicine.